[{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5814,"experimentAnswers.text":"0, 3, 6, 9, 12, 15, 21, 24 h","experimentAnswers.answerId":null,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":121,"experimentAnswers.question.id":121,"experimentAnswers.question.text":"Times of PK samples for object","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5846,"experimentAnswers.text":"Once","experimentAnswers.answerId":null,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":111,"experimentAnswers.question.id":111,"experimentAnswers.question.text":"Interval/frequency","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5845,"experimentAnswers.text":"Not specified","experimentAnswers.answerId":null,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":132,"experimentAnswers.question.id":132,"experimentAnswers.question.text":"Year sourcing was completed","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5831,"experimentAnswers.text":"Fed (no. of events, n=12)
Nervous system disorders:
Dizziness 3
Paraesthesia 1
Somnolence 1
Psychiatric disorders:
Daydreaming 1
Dissociation 0
Euphoric mood 1
Inappropriate effect 1
Metabolism and nutrition disorders: Increased appetite 1
Respiratory, thoracic and mediastinal disorders: Dry throat 1
Injury, poisoning and procedural complications: Procedural site reaction 1
Fasted (no. of events, n=12)
Somnolence 1
Feeling abnormal 1","experimentAnswers.answerId":null,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":127,"experimentAnswers.question.id":127,"experimentAnswers.question.text":"Pharmacodynamic results","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"TEXT","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5844,"experimentAnswers.text":"10.8 mg THC + 10 mg CBD","experimentAnswers.answerId":null,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":110,"experimentAnswers.question.id":110,"experimentAnswers.question.text":"Total daily dose","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5830,"experimentAnswers.text":"No serious AEs (SAEs) were reported during the course of this study, and all AEs were classified as being mild in severity. All AEs occurring in one or more subjects are presented in Table 3. The most common AE was dizziness in 3 fed subjects. Four AEs were reported by 2 fasted subjects (17%) and 11 AEs were reported by 7 fed subjects (58%), suggesting that THC/CBD spray might be better tolerated by subjects under fasted conditions. However, there was no apparent relationship between the occurrence of AEs and the PKs in these subjects. In the subjects who experienced an AE in the fed state, the Cmax for THC was higher than in the fasted state in 3 subjects, but was lower than in the fasted state in 4 subjects.","experimentAnswers.answerId":null,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":129,"experimentAnswers.question.id":129,"experimentAnswers.question.text":"Safety results","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"TEXT","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5813,"experimentAnswers.text":"Subjects were 19 to 44 years of age with a mean (SD) age of 28.5 (7.55) years. Subjects’ BMI ranged from 18 to 28 kg/m2 with a mean (SD) BMI of 24.8 (2.99) kg/m2 and a mean (SD) bodyweight of 74.02 (11.25) kg at screening. Of the 12 subjects who took part, 8 were white/Caucasian, 2 were black/African–American and 2 were Asian in ethnicity. All subjects were considered healthy at screening and admission and the investigator did not consider any of the reported medical history abnormalities to preclude the participation of any of the subjects who entered into the trial. Additionally, all subjects tested negative for CBs during screening and at admission.","experimentAnswers.answerId":null,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":107,"experimentAnswers.question.id":107,"experimentAnswers.question.text":"Population additional information","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"TEXT","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5829,"experimentAnswers.text":"At each visit (during each session) the incidence of adverse events (AEs) was recorded. Laboratory parameters, vital signs, physical examination, oral examination, and checks on concomitant medication were also performed. The reference ranges for vital signs were 34–100 bpm for standing pulse rate, 90–160 mmHg for standing systolic blood pressure and 40–100 mmHg for standing diastolic blood pressure. A clinically significant change was defined as a change from baseline of at least 20 mmHg in systolic blood pressure, of 10 mmHg in diastolic blood pressure and of 10 bpm in pulse rate.","experimentAnswers.answerId":null,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":125,"experimentAnswers.question.id":125,"experimentAnswers.question.text":"Pharmacodynamic protocol","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"TEXT","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5843,"experimentAnswers.text":"Oromucosal spray","experimentAnswers.answerId":null,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":109,"experimentAnswers.question.id":109,"experimentAnswers.question.text":"Formulation","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5842,"experimentAnswers.text":"Standardized meals","experimentAnswers.answerId":null,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":131,"experimentAnswers.question.id":131,"experimentAnswers.question.text":"Prandial state comment","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5841,"experimentAnswers.text":"The THC/CBD spray is a solution containing ethanol, propylene glycol and peppermint oil flavouring for oromucosal use through a sealed pump-action spray device, which was delivered either underneath the tongue, or to the inside of the cheek.","experimentAnswers.answerId":null,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":120,"experimentAnswers.question.id":120,"experimentAnswers.question.text":"Natural product additional information","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"TEXT","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5812,"experimentAnswers.text":"12","experimentAnswers.answerId":null,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":106,"experimentAnswers.question.id":106,"experimentAnswers.question.text":"Number of subjects","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":null,"experimentAnswers.question.type":"STRING","experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":null,"experimentAnswers.question.answers.text":null,"experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":null,"experimentAnswers.answer.id":null,"experimentAnswers.answer.text":null,"experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":null},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":1532,"experimentAnswers.question.answers.text":"Therapeutic drug effect","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":4004994,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":1531,"experimentAnswers.question.answers.text":"Paced auditory serial addition test","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":4151973,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":1529,"experimentAnswers.question.answers.text":"Cognitive test","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":1527,"experimentAnswers.question.answers.text":"Memory impairment","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36718175,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":1526,"experimentAnswers.question.answers.text":"Drug effect increased","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35809325,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":1525,"experimentAnswers.question.answers.text":"Drug side effect","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35843643,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":1524,"experimentAnswers.question.answers.text":"Heart rate","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36311980,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":1523,"experimentAnswers.question.answers.text":"Blood pressure measurement","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":46276597,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5839,"experimentAnswers.text":null,"experimentAnswers.answerId":600,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":108,"experimentAnswers.question.id":108,"experimentAnswers.question.text":"Administration route","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":606,"experimentAnswers.question.answers.text":"Sublingual","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":108,"experimentAnswers.answer.id":600,"experimentAnswers.answer.text":"Oral","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":108},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5839,"experimentAnswers.text":null,"experimentAnswers.answerId":600,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":108,"experimentAnswers.question.id":108,"experimentAnswers.question.text":"Administration route","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":605,"experimentAnswers.question.answers.text":"Buccal","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":108,"experimentAnswers.answer.id":600,"experimentAnswers.answer.text":"Oral","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":108},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":825,"experimentAnswers.question.answers.text":"Vascular disorder","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37600000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":824,"experimentAnswers.question.answers.text":"Surgical and medical procedures","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37500000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":823,"experimentAnswers.question.answers.text":"Social circumstances","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37400000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":822,"experimentAnswers.question.answers.text":"Skin and subcutaneous tissue disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37300000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":821,"experimentAnswers.question.answers.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37200000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":820,"experimentAnswers.question.answers.text":"Reproductive system and breast disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37100000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":819,"experimentAnswers.question.answers.text":"Renal and urinary disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37000000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":818,"experimentAnswers.question.answers.text":"Psychiatric disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36900000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":817,"experimentAnswers.question.answers.text":"Pregnancy, puerperium and perinatal conditions","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36800000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":816,"experimentAnswers.question.answers.text":"Nervous system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36800000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":815,"experimentAnswers.question.answers.text":"Neoplasms benign, malignant and unspecified (incl cysts and polyps)","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36600000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":814,"experimentAnswers.question.answers.text":"Musculoskeletal and connective tissue disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36500000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":813,"experimentAnswers.question.answers.text":"Metabolism and nutrition disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36400000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":812,"experimentAnswers.question.answers.text":"Investigations","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36300000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":811,"experimentAnswers.question.answers.text":"Injury, poisoning and procedural complications","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36200000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":810,"experimentAnswers.question.answers.text":"Infections and infestations","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36100000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":809,"experimentAnswers.question.answers.text":"Immune system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36000000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":808,"experimentAnswers.question.answers.text":"Hepatobiliary disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35900000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":807,"experimentAnswers.question.answers.text":"General disorders and administration site conditions","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35800000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":806,"experimentAnswers.question.answers.text":"Gastrointestinal disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35800000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":805,"experimentAnswers.question.answers.text":"Eye disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35600000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":804,"experimentAnswers.question.answers.text":"Endocrine disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35500000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":803,"experimentAnswers.question.answers.text":"Ear and labyrinth disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35400000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":802,"experimentAnswers.question.answers.text":"Congenital, familial and genetic disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35300000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":801,"experimentAnswers.question.answers.text":"Cardiac disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35200000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5828,"experimentAnswers.text":null,"experimentAnswers.answerId":801,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":126,"experimentAnswers.question.id":126,"experimentAnswers.question.text":"Pharmacodynamic measurement classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":800,"experimentAnswers.question.answers.text":"Blood and lymphatic system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35100000,"experimentAnswers.question.answers.questionId":126,"experimentAnswers.answer.id":801,"experimentAnswers.answer.text":"Cardiac disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35200000,"experimentAnswers.answer.questionId":126},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":725,"experimentAnswers.question.answers.text":"Vascular disorder","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37600000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":725,"experimentAnswers.question.answers.text":"Vascular disorder","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37600000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":725,"experimentAnswers.question.answers.text":"Vascular disorder","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37600000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":725,"experimentAnswers.question.answers.text":"Vascular disorder","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37600000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":725,"experimentAnswers.question.answers.text":"Vascular disorder","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37600000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":725,"experimentAnswers.question.answers.text":"Vascular disorder","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37600000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":724,"experimentAnswers.question.answers.text":"Surgical and medical procedures","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37500000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":724,"experimentAnswers.question.answers.text":"Surgical and medical procedures","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37500000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":724,"experimentAnswers.question.answers.text":"Surgical and medical procedures","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37500000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":724,"experimentAnswers.question.answers.text":"Surgical and medical procedures","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37500000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":724,"experimentAnswers.question.answers.text":"Surgical and medical procedures","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37500000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":724,"experimentAnswers.question.answers.text":"Surgical and medical procedures","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37500000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":723,"experimentAnswers.question.answers.text":"Social circumstances","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37400000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":723,"experimentAnswers.question.answers.text":"Social circumstances","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37400000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":723,"experimentAnswers.question.answers.text":"Social circumstances","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37400000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":723,"experimentAnswers.question.answers.text":"Social circumstances","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37400000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":723,"experimentAnswers.question.answers.text":"Social circumstances","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37400000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":723,"experimentAnswers.question.answers.text":"Social circumstances","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37400000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":722,"experimentAnswers.question.answers.text":"Skin and subcutaneous tissue disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37300000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":722,"experimentAnswers.question.answers.text":"Skin and subcutaneous tissue disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37300000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":722,"experimentAnswers.question.answers.text":"Skin and subcutaneous tissue disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37300000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":722,"experimentAnswers.question.answers.text":"Skin and subcutaneous tissue disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37300000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":722,"experimentAnswers.question.answers.text":"Skin and subcutaneous tissue disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37300000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":722,"experimentAnswers.question.answers.text":"Skin and subcutaneous tissue disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37300000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":721,"experimentAnswers.question.answers.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37200000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":721,"experimentAnswers.question.answers.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37200000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":721,"experimentAnswers.question.answers.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37200000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":721,"experimentAnswers.question.answers.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37200000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":721,"experimentAnswers.question.answers.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37200000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":721,"experimentAnswers.question.answers.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37200000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":720,"experimentAnswers.question.answers.text":"Reproductive system and breast disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37100000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":720,"experimentAnswers.question.answers.text":"Reproductive system and breast disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37100000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":720,"experimentAnswers.question.answers.text":"Reproductive system and breast disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37100000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":720,"experimentAnswers.question.answers.text":"Reproductive system and breast disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37100000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":720,"experimentAnswers.question.answers.text":"Reproductive system and breast disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37100000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":720,"experimentAnswers.question.answers.text":"Reproductive system and breast disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37100000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5840,"experimentAnswers.text":null,"experimentAnswers.answerId":900,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":130,"experimentAnswers.question.id":130,"experimentAnswers.question.text":"Prandial state","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":901,"experimentAnswers.question.answers.text":"Fasted","experimentAnswers.question.answers.sortOrder":20,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":130,"experimentAnswers.answer.id":900,"experimentAnswers.answer.text":"Fed","experimentAnswers.answer.sortOrder":10,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":130},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5840,"experimentAnswers.text":null,"experimentAnswers.answerId":900,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":130,"experimentAnswers.question.id":130,"experimentAnswers.question.text":"Prandial state","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":900,"experimentAnswers.question.answers.text":"Fed","experimentAnswers.question.answers.sortOrder":10,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":130,"experimentAnswers.answer.id":900,"experimentAnswers.answer.text":"Fed","experimentAnswers.answer.sortOrder":10,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":130},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5810,"experimentAnswers.text":null,"experimentAnswers.answerId":105,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":100,"experimentAnswers.question.id":100,"experimentAnswers.question.text":"Study design","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":107,"experimentAnswers.question.answers.text":"Multiple dosing","experimentAnswers.question.answers.sortOrder":80,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":100,"experimentAnswers.answer.id":105,"experimentAnswers.answer.text":"Randomized crossover","experimentAnswers.answer.sortOrder":60,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":100},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5811,"experimentAnswers.text":null,"experimentAnswers.answerId":106,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":100,"experimentAnswers.question.id":100,"experimentAnswers.question.text":"Study design","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":107,"experimentAnswers.question.answers.text":"Multiple dosing","experimentAnswers.question.answers.sortOrder":80,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":100,"experimentAnswers.answer.id":106,"experimentAnswers.answer.text":"Single dosing","experimentAnswers.answer.sortOrder":70,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":100},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5810,"experimentAnswers.text":null,"experimentAnswers.answerId":105,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":100,"experimentAnswers.question.id":100,"experimentAnswers.question.text":"Study design","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":106,"experimentAnswers.question.answers.text":"Single dosing","experimentAnswers.question.answers.sortOrder":70,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":100,"experimentAnswers.answer.id":105,"experimentAnswers.answer.text":"Randomized crossover","experimentAnswers.answer.sortOrder":60,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":100},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5811,"experimentAnswers.text":null,"experimentAnswers.answerId":106,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":100,"experimentAnswers.question.id":100,"experimentAnswers.question.text":"Study design","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":106,"experimentAnswers.question.answers.text":"Single dosing","experimentAnswers.question.answers.sortOrder":70,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":100,"experimentAnswers.answer.id":106,"experimentAnswers.answer.text":"Single dosing","experimentAnswers.answer.sortOrder":70,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":100},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5810,"experimentAnswers.text":null,"experimentAnswers.answerId":105,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":100,"experimentAnswers.question.id":100,"experimentAnswers.question.text":"Study design","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":105,"experimentAnswers.question.answers.text":"Randomized crossover","experimentAnswers.question.answers.sortOrder":60,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":100,"experimentAnswers.answer.id":105,"experimentAnswers.answer.text":"Randomized crossover","experimentAnswers.answer.sortOrder":60,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":100},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5811,"experimentAnswers.text":null,"experimentAnswers.answerId":106,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":100,"experimentAnswers.question.id":100,"experimentAnswers.question.text":"Study design","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":105,"experimentAnswers.question.answers.text":"Randomized crossover","experimentAnswers.question.answers.sortOrder":60,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":100,"experimentAnswers.answer.id":106,"experimentAnswers.answer.text":"Single dosing","experimentAnswers.answer.sortOrder":70,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":100},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5810,"experimentAnswers.text":null,"experimentAnswers.answerId":105,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":100,"experimentAnswers.question.id":100,"experimentAnswers.question.text":"Study design","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":104,"experimentAnswers.question.answers.text":"Placebo-controlled","experimentAnswers.question.answers.sortOrder":50,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":100,"experimentAnswers.answer.id":105,"experimentAnswers.answer.text":"Randomized crossover","experimentAnswers.answer.sortOrder":60,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":100},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5811,"experimentAnswers.text":null,"experimentAnswers.answerId":106,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":100,"experimentAnswers.question.id":100,"experimentAnswers.question.text":"Study design","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":104,"experimentAnswers.question.answers.text":"Placebo-controlled","experimentAnswers.question.answers.sortOrder":50,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":100,"experimentAnswers.answer.id":106,"experimentAnswers.answer.text":"Single dosing","experimentAnswers.answer.sortOrder":70,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":100},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5810,"experimentAnswers.text":null,"experimentAnswers.answerId":105,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":100,"experimentAnswers.question.id":100,"experimentAnswers.question.text":"Study design","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":103,"experimentAnswers.question.answers.text":"Parallel","experimentAnswers.question.answers.sortOrder":40,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":100,"experimentAnswers.answer.id":105,"experimentAnswers.answer.text":"Randomized crossover","experimentAnswers.answer.sortOrder":60,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":100},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5811,"experimentAnswers.text":null,"experimentAnswers.answerId":106,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":100,"experimentAnswers.question.id":100,"experimentAnswers.question.text":"Study design","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":103,"experimentAnswers.question.answers.text":"Parallel","experimentAnswers.question.answers.sortOrder":40,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":100,"experimentAnswers.answer.id":106,"experimentAnswers.answer.text":"Single dosing","experimentAnswers.answer.sortOrder":70,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":100},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5810,"experimentAnswers.text":null,"experimentAnswers.answerId":105,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":100,"experimentAnswers.question.id":100,"experimentAnswers.question.text":"Study design","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":102,"experimentAnswers.question.answers.text":"Fixed-sequence","experimentAnswers.question.answers.sortOrder":30,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":100,"experimentAnswers.answer.id":105,"experimentAnswers.answer.text":"Randomized crossover","experimentAnswers.answer.sortOrder":60,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":100},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5811,"experimentAnswers.text":null,"experimentAnswers.answerId":106,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":100,"experimentAnswers.question.id":100,"experimentAnswers.question.text":"Study design","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":102,"experimentAnswers.question.answers.text":"Fixed-sequence","experimentAnswers.question.answers.sortOrder":30,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":100,"experimentAnswers.answer.id":106,"experimentAnswers.answer.text":"Single dosing","experimentAnswers.answer.sortOrder":70,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":100},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5810,"experimentAnswers.text":null,"experimentAnswers.answerId":105,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":100,"experimentAnswers.question.id":100,"experimentAnswers.question.text":"Study design","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":101,"experimentAnswers.question.answers.text":"Double-blind","experimentAnswers.question.answers.sortOrder":20,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":100,"experimentAnswers.answer.id":105,"experimentAnswers.answer.text":"Randomized crossover","experimentAnswers.answer.sortOrder":60,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":100},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5811,"experimentAnswers.text":null,"experimentAnswers.answerId":106,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":100,"experimentAnswers.question.id":100,"experimentAnswers.question.text":"Study design","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":101,"experimentAnswers.question.answers.text":"Double-blind","experimentAnswers.question.answers.sortOrder":20,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":100,"experimentAnswers.answer.id":106,"experimentAnswers.answer.text":"Single dosing","experimentAnswers.answer.sortOrder":70,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":100},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5810,"experimentAnswers.text":null,"experimentAnswers.answerId":105,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":100,"experimentAnswers.question.id":100,"experimentAnswers.question.text":"Study design","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":100,"experimentAnswers.question.answers.text":"Probe cocktail study","experimentAnswers.question.answers.sortOrder":10,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":100,"experimentAnswers.answer.id":105,"experimentAnswers.answer.text":"Randomized crossover","experimentAnswers.answer.sortOrder":60,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":100},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5811,"experimentAnswers.text":null,"experimentAnswers.answerId":106,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":100,"experimentAnswers.question.id":100,"experimentAnswers.question.text":"Study design","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":100,"experimentAnswers.question.answers.text":"Probe cocktail study","experimentAnswers.question.answers.sortOrder":10,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":100,"experimentAnswers.answer.id":106,"experimentAnswers.answer.text":"Single dosing","experimentAnswers.answer.sortOrder":70,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":100},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":719,"experimentAnswers.question.answers.text":"Renal and urinary disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37000000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":719,"experimentAnswers.question.answers.text":"Renal and urinary disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37000000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":719,"experimentAnswers.question.answers.text":"Renal and urinary disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37000000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":719,"experimentAnswers.question.answers.text":"Renal and urinary disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37000000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":719,"experimentAnswers.question.answers.text":"Renal and urinary disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37000000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":719,"experimentAnswers.question.answers.text":"Renal and urinary disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":37000000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":718,"experimentAnswers.question.answers.text":"Psychiatric disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36900000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":718,"experimentAnswers.question.answers.text":"Psychiatric disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36900000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":718,"experimentAnswers.question.answers.text":"Psychiatric disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36900000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":718,"experimentAnswers.question.answers.text":"Psychiatric disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36900000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":718,"experimentAnswers.question.answers.text":"Psychiatric disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36900000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":718,"experimentAnswers.question.answers.text":"Psychiatric disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36900000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":715,"experimentAnswers.question.answers.text":"Neoplasms benign, malignant and unspecified (incl cysts and polyps)","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36600000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":715,"experimentAnswers.question.answers.text":"Neoplasms benign, malignant and unspecified (incl cysts and polyps)","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36600000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":715,"experimentAnswers.question.answers.text":"Neoplasms benign, malignant and unspecified (incl cysts and polyps)","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36600000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":715,"experimentAnswers.question.answers.text":"Neoplasms benign, malignant and unspecified (incl cysts and polyps)","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36600000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":715,"experimentAnswers.question.answers.text":"Neoplasms benign, malignant and unspecified (incl cysts and polyps)","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36600000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":715,"experimentAnswers.question.answers.text":"Neoplasms benign, malignant and unspecified (incl cysts and polyps)","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36600000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":707,"experimentAnswers.question.answers.text":"General disorders and administration site conditions","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35800000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":707,"experimentAnswers.question.answers.text":"General disorders and administration site conditions","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35800000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":707,"experimentAnswers.question.answers.text":"General disorders and administration site conditions","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35800000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":707,"experimentAnswers.question.answers.text":"General disorders and administration site conditions","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35800000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":707,"experimentAnswers.question.answers.text":"General disorders and administration site conditions","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35800000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":707,"experimentAnswers.question.answers.text":"General disorders and administration site conditions","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35800000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":700,"experimentAnswers.question.answers.text":"Blood and lymphatic system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35100000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":700,"experimentAnswers.question.answers.text":"Blood and lymphatic system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35100000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":700,"experimentAnswers.question.answers.text":"Blood and lymphatic system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35100000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":700,"experimentAnswers.question.answers.text":"Blood and lymphatic system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35100000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":700,"experimentAnswers.question.answers.text":"Blood and lymphatic system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35100000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":700,"experimentAnswers.question.answers.text":"Blood and lymphatic system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35100000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":717,"experimentAnswers.question.answers.text":"Pregnancy, puerperium and perinatal conditions","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36800000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":717,"experimentAnswers.question.answers.text":"Pregnancy, puerperium and perinatal conditions","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36800000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":717,"experimentAnswers.question.answers.text":"Pregnancy, puerperium and perinatal conditions","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36800000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":717,"experimentAnswers.question.answers.text":"Pregnancy, puerperium and perinatal conditions","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36800000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":717,"experimentAnswers.question.answers.text":"Pregnancy, puerperium and perinatal conditions","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36800000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":717,"experimentAnswers.question.answers.text":"Pregnancy, puerperium and perinatal conditions","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36800000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":716,"experimentAnswers.question.answers.text":"Nervous system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36700000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":716,"experimentAnswers.question.answers.text":"Nervous system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36700000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":716,"experimentAnswers.question.answers.text":"Nervous system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36700000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":716,"experimentAnswers.question.answers.text":"Nervous system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36700000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":716,"experimentAnswers.question.answers.text":"Nervous system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36700000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":716,"experimentAnswers.question.answers.text":"Nervous system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36700000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":714,"experimentAnswers.question.answers.text":"Musculoskeletal and connective tissue disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36500000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":714,"experimentAnswers.question.answers.text":"Musculoskeletal and connective tissue disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36500000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":714,"experimentAnswers.question.answers.text":"Musculoskeletal and connective tissue disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36500000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":714,"experimentAnswers.question.answers.text":"Musculoskeletal and connective tissue disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36500000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":714,"experimentAnswers.question.answers.text":"Musculoskeletal and connective tissue disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36500000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":714,"experimentAnswers.question.answers.text":"Musculoskeletal and connective tissue disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36500000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":713,"experimentAnswers.question.answers.text":"Metabolism and nutrition disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36400000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":713,"experimentAnswers.question.answers.text":"Metabolism and nutrition disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36400000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":713,"experimentAnswers.question.answers.text":"Metabolism and nutrition disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36400000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":713,"experimentAnswers.question.answers.text":"Metabolism and nutrition disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36400000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":713,"experimentAnswers.question.answers.text":"Metabolism and nutrition disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36400000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":713,"experimentAnswers.question.answers.text":"Metabolism and nutrition disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36400000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":712,"experimentAnswers.question.answers.text":"Investigations","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36300000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":712,"experimentAnswers.question.answers.text":"Investigations","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36300000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":712,"experimentAnswers.question.answers.text":"Investigations","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36300000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":712,"experimentAnswers.question.answers.text":"Investigations","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36300000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":712,"experimentAnswers.question.answers.text":"Investigations","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36300000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":712,"experimentAnswers.question.answers.text":"Investigations","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36300000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":711,"experimentAnswers.question.answers.text":"Injury, poisoning and procedural complications","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36200000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":711,"experimentAnswers.question.answers.text":"Injury, poisoning and procedural complications","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36200000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":711,"experimentAnswers.question.answers.text":"Injury, poisoning and procedural complications","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36200000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":711,"experimentAnswers.question.answers.text":"Injury, poisoning and procedural complications","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36200000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":711,"experimentAnswers.question.answers.text":"Injury, poisoning and procedural complications","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36200000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":711,"experimentAnswers.question.answers.text":"Injury, poisoning and procedural complications","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36200000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":710,"experimentAnswers.question.answers.text":"Infections and infestations","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36100000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":710,"experimentAnswers.question.answers.text":"Infections and infestations","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36100000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":710,"experimentAnswers.question.answers.text":"Infections and infestations","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36100000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":710,"experimentAnswers.question.answers.text":"Infections and infestations","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36100000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":710,"experimentAnswers.question.answers.text":"Infections and infestations","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36100000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":710,"experimentAnswers.question.answers.text":"Infections and infestations","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36100000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":709,"experimentAnswers.question.answers.text":"Immune system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36000000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":709,"experimentAnswers.question.answers.text":"Immune system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36000000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":709,"experimentAnswers.question.answers.text":"Immune system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36000000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":709,"experimentAnswers.question.answers.text":"Immune system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36000000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":709,"experimentAnswers.question.answers.text":"Immune system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36000000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":709,"experimentAnswers.question.answers.text":"Immune system disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":36000000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":708,"experimentAnswers.question.answers.text":"Hepatobiliary disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35900000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":708,"experimentAnswers.question.answers.text":"Hepatobiliary disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35900000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":708,"experimentAnswers.question.answers.text":"Hepatobiliary disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35900000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":708,"experimentAnswers.question.answers.text":"Hepatobiliary disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35900000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":708,"experimentAnswers.question.answers.text":"Hepatobiliary disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35900000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":708,"experimentAnswers.question.answers.text":"Hepatobiliary disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35900000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":706,"experimentAnswers.question.answers.text":"Gastrointestinal disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35700000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":706,"experimentAnswers.question.answers.text":"Gastrointestinal disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35700000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":706,"experimentAnswers.question.answers.text":"Gastrointestinal disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35700000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":706,"experimentAnswers.question.answers.text":"Gastrointestinal disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35700000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":706,"experimentAnswers.question.answers.text":"Gastrointestinal disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35700000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":706,"experimentAnswers.question.answers.text":"Gastrointestinal disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35700000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":705,"experimentAnswers.question.answers.text":"Eye disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35600000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":705,"experimentAnswers.question.answers.text":"Eye disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35600000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":705,"experimentAnswers.question.answers.text":"Eye disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35600000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":705,"experimentAnswers.question.answers.text":"Eye disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35600000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":705,"experimentAnswers.question.answers.text":"Eye disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35600000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":705,"experimentAnswers.question.answers.text":"Eye disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35600000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":704,"experimentAnswers.question.answers.text":"Endocrine disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35500000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":704,"experimentAnswers.question.answers.text":"Endocrine disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35500000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":704,"experimentAnswers.question.answers.text":"Endocrine disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35500000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":704,"experimentAnswers.question.answers.text":"Endocrine disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35500000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":704,"experimentAnswers.question.answers.text":"Endocrine disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35500000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":704,"experimentAnswers.question.answers.text":"Endocrine disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35500000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5839,"experimentAnswers.text":null,"experimentAnswers.answerId":600,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":108,"experimentAnswers.question.id":108,"experimentAnswers.question.text":"Administration route","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":604,"experimentAnswers.question.answers.text":"Inhalation","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":108,"experimentAnswers.answer.id":600,"experimentAnswers.answer.text":"Oral","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":108},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5839,"experimentAnswers.text":null,"experimentAnswers.answerId":600,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":108,"experimentAnswers.question.id":108,"experimentAnswers.question.text":"Administration route","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":603,"experimentAnswers.question.answers.text":"Intramuscular","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":108,"experimentAnswers.answer.id":600,"experimentAnswers.answer.text":"Oral","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":108},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5839,"experimentAnswers.text":null,"experimentAnswers.answerId":600,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":108,"experimentAnswers.question.id":108,"experimentAnswers.question.text":"Administration route","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":602,"experimentAnswers.question.answers.text":"Transdermal","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":108,"experimentAnswers.answer.id":600,"experimentAnswers.answer.text":"Oral","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":108},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5839,"experimentAnswers.text":null,"experimentAnswers.answerId":600,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":108,"experimentAnswers.question.id":108,"experimentAnswers.question.text":"Administration route","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":601,"experimentAnswers.question.answers.text":"Intravenous","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":108,"experimentAnswers.answer.id":600,"experimentAnswers.answer.text":"Oral","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":108},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5839,"experimentAnswers.text":null,"experimentAnswers.answerId":600,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":108,"experimentAnswers.question.id":108,"experimentAnswers.question.text":"Administration route","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":1,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":600,"experimentAnswers.question.answers.text":"Oral","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":108,"experimentAnswers.answer.id":600,"experimentAnswers.answer.text":"Oral","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":108},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5807,"experimentAnswers.text":null,"experimentAnswers.answerId":403,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":407,"experimentAnswers.question.answers.text":"More than one race","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":403,"experimentAnswers.answer.text":"Asian","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5808,"experimentAnswers.text":null,"experimentAnswers.answerId":405,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":407,"experimentAnswers.question.answers.text":"More than one race","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":405,"experimentAnswers.answer.text":"Black or African American","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5809,"experimentAnswers.text":null,"experimentAnswers.answerId":406,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":407,"experimentAnswers.question.answers.text":"More than one race","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":406,"experimentAnswers.answer.text":"White","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5807,"experimentAnswers.text":null,"experimentAnswers.answerId":403,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":406,"experimentAnswers.question.answers.text":"White","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":403,"experimentAnswers.answer.text":"Asian","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5808,"experimentAnswers.text":null,"experimentAnswers.answerId":405,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":406,"experimentAnswers.question.answers.text":"White","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":405,"experimentAnswers.answer.text":"Black or African American","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5809,"experimentAnswers.text":null,"experimentAnswers.answerId":406,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":406,"experimentAnswers.question.answers.text":"White","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":406,"experimentAnswers.answer.text":"White","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5807,"experimentAnswers.text":null,"experimentAnswers.answerId":403,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":405,"experimentAnswers.question.answers.text":"Black or African American","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":403,"experimentAnswers.answer.text":"Asian","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5808,"experimentAnswers.text":null,"experimentAnswers.answerId":405,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":405,"experimentAnswers.question.answers.text":"Black or African American","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":405,"experimentAnswers.answer.text":"Black or African American","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5809,"experimentAnswers.text":null,"experimentAnswers.answerId":406,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":405,"experimentAnswers.question.answers.text":"Black or African American","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":406,"experimentAnswers.answer.text":"White","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5807,"experimentAnswers.text":null,"experimentAnswers.answerId":403,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":404,"experimentAnswers.question.answers.text":"Native Hawaiian or Other Pacific Islander","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":403,"experimentAnswers.answer.text":"Asian","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5808,"experimentAnswers.text":null,"experimentAnswers.answerId":405,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":404,"experimentAnswers.question.answers.text":"Native Hawaiian or Other Pacific Islander","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":405,"experimentAnswers.answer.text":"Black or African American","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5809,"experimentAnswers.text":null,"experimentAnswers.answerId":406,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":404,"experimentAnswers.question.answers.text":"Native Hawaiian or Other Pacific Islander","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":406,"experimentAnswers.answer.text":"White","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5807,"experimentAnswers.text":null,"experimentAnswers.answerId":403,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":403,"experimentAnswers.question.answers.text":"Asian","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":403,"experimentAnswers.answer.text":"Asian","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5808,"experimentAnswers.text":null,"experimentAnswers.answerId":405,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":403,"experimentAnswers.question.answers.text":"Asian","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":405,"experimentAnswers.answer.text":"Black or African American","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5809,"experimentAnswers.text":null,"experimentAnswers.answerId":406,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":403,"experimentAnswers.question.answers.text":"Asian","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":406,"experimentAnswers.answer.text":"White","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5807,"experimentAnswers.text":null,"experimentAnswers.answerId":403,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":402,"experimentAnswers.question.answers.text":"American Indian or Alaska native","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":403,"experimentAnswers.answer.text":"Asian","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5808,"experimentAnswers.text":null,"experimentAnswers.answerId":405,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":402,"experimentAnswers.question.answers.text":"American Indian or Alaska native","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":405,"experimentAnswers.answer.text":"Black or African American","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5809,"experimentAnswers.text":null,"experimentAnswers.answerId":406,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":402,"experimentAnswers.question.answers.text":"American Indian or Alaska native","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":406,"experimentAnswers.answer.text":"White","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5807,"experimentAnswers.text":null,"experimentAnswers.answerId":403,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":401,"experimentAnswers.question.answers.text":"Hispanic or Latino","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":403,"experimentAnswers.answer.text":"Asian","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5808,"experimentAnswers.text":null,"experimentAnswers.answerId":405,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":401,"experimentAnswers.question.answers.text":"Hispanic or Latino","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":405,"experimentAnswers.answer.text":"Black or African American","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5809,"experimentAnswers.text":null,"experimentAnswers.answerId":406,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":401,"experimentAnswers.question.answers.text":"Hispanic or Latino","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":406,"experimentAnswers.answer.text":"White","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5807,"experimentAnswers.text":null,"experimentAnswers.answerId":403,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":400,"experimentAnswers.question.answers.text":"Not Hispanic or Latino","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":403,"experimentAnswers.answer.text":"Asian","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5808,"experimentAnswers.text":null,"experimentAnswers.answerId":405,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":400,"experimentAnswers.question.answers.text":"Not Hispanic or Latino","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":405,"experimentAnswers.answer.text":"Black or African American","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5809,"experimentAnswers.text":null,"experimentAnswers.answerId":406,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":103,"experimentAnswers.question.id":103,"experimentAnswers.question.text":"Ethnicity","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":400,"experimentAnswers.question.answers.text":"Not Hispanic or Latino","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":103,"experimentAnswers.answer.id":406,"experimentAnswers.answer.text":"White","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":103},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5804,"experimentAnswers.text":null,"experimentAnswers.answerId":300,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":307,"experimentAnswers.question.answers.text":"Regular marijuana use","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":300,"experimentAnswers.answer.text":"Nonsmokers","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5805,"experimentAnswers.text":null,"experimentAnswers.answerId":302,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":307,"experimentAnswers.question.answers.text":"Regular marijuana use","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":302,"experimentAnswers.answer.text":"No alcohol drinking","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5806,"experimentAnswers.text":null,"experimentAnswers.answerId":305,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":307,"experimentAnswers.question.answers.text":"Regular marijuana use","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":305,"experimentAnswers.answer.text":"No marijuana use","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5804,"experimentAnswers.text":null,"experimentAnswers.answerId":300,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":306,"experimentAnswers.question.answers.text":"Occasional marijuana use","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":300,"experimentAnswers.answer.text":"Nonsmokers","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5805,"experimentAnswers.text":null,"experimentAnswers.answerId":302,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":306,"experimentAnswers.question.answers.text":"Occasional marijuana use","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":302,"experimentAnswers.answer.text":"No alcohol drinking","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5806,"experimentAnswers.text":null,"experimentAnswers.answerId":305,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":306,"experimentAnswers.question.answers.text":"Occasional marijuana use","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":305,"experimentAnswers.answer.text":"No marijuana use","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5804,"experimentAnswers.text":null,"experimentAnswers.answerId":300,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":305,"experimentAnswers.question.answers.text":"No marijuana use","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":300,"experimentAnswers.answer.text":"Nonsmokers","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5805,"experimentAnswers.text":null,"experimentAnswers.answerId":302,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":305,"experimentAnswers.question.answers.text":"No marijuana use","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":302,"experimentAnswers.answer.text":"No alcohol drinking","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5806,"experimentAnswers.text":null,"experimentAnswers.answerId":305,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":305,"experimentAnswers.question.answers.text":"No marijuana use","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":305,"experimentAnswers.answer.text":"No marijuana use","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5804,"experimentAnswers.text":null,"experimentAnswers.answerId":300,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":304,"experimentAnswers.question.answers.text":"Unhealthy alcohol drinking ","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":300,"experimentAnswers.answer.text":"Nonsmokers","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5805,"experimentAnswers.text":null,"experimentAnswers.answerId":302,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":304,"experimentAnswers.question.answers.text":"Unhealthy alcohol drinking ","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":302,"experimentAnswers.answer.text":"No alcohol drinking","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5806,"experimentAnswers.text":null,"experimentAnswers.answerId":305,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":304,"experimentAnswers.question.answers.text":"Unhealthy alcohol drinking ","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":305,"experimentAnswers.answer.text":"No marijuana use","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5804,"experimentAnswers.text":null,"experimentAnswers.answerId":300,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":303,"experimentAnswers.question.answers.text":"Healthy alcohol drinking","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":300,"experimentAnswers.answer.text":"Nonsmokers","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5805,"experimentAnswers.text":null,"experimentAnswers.answerId":302,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":303,"experimentAnswers.question.answers.text":"Healthy alcohol drinking","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":302,"experimentAnswers.answer.text":"No alcohol drinking","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5806,"experimentAnswers.text":null,"experimentAnswers.answerId":305,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":303,"experimentAnswers.question.answers.text":"Healthy alcohol drinking","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":305,"experimentAnswers.answer.text":"No marijuana use","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5804,"experimentAnswers.text":null,"experimentAnswers.answerId":300,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":302,"experimentAnswers.question.answers.text":"No alcohol drinking","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":300,"experimentAnswers.answer.text":"Nonsmokers","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5805,"experimentAnswers.text":null,"experimentAnswers.answerId":302,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":302,"experimentAnswers.question.answers.text":"No alcohol drinking","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":302,"experimentAnswers.answer.text":"No alcohol drinking","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5806,"experimentAnswers.text":null,"experimentAnswers.answerId":305,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":302,"experimentAnswers.question.answers.text":"No alcohol drinking","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":305,"experimentAnswers.answer.text":"No marijuana use","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5804,"experimentAnswers.text":null,"experimentAnswers.answerId":300,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":301,"experimentAnswers.question.answers.text":"Smokers","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":300,"experimentAnswers.answer.text":"Nonsmokers","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5805,"experimentAnswers.text":null,"experimentAnswers.answerId":302,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":301,"experimentAnswers.question.answers.text":"Smokers","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":302,"experimentAnswers.answer.text":"No alcohol drinking","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5806,"experimentAnswers.text":null,"experimentAnswers.answerId":305,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":301,"experimentAnswers.question.answers.text":"Smokers","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":305,"experimentAnswers.answer.text":"No marijuana use","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5804,"experimentAnswers.text":null,"experimentAnswers.answerId":300,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":300,"experimentAnswers.question.answers.text":"Nonsmokers","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":300,"experimentAnswers.answer.text":"Nonsmokers","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5805,"experimentAnswers.text":null,"experimentAnswers.answerId":302,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":300,"experimentAnswers.question.answers.text":"Nonsmokers","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":302,"experimentAnswers.answer.text":"No alcohol drinking","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5806,"experimentAnswers.text":null,"experimentAnswers.answerId":305,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":102,"experimentAnswers.question.id":102,"experimentAnswers.question.text":"Lifestyle factors","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":300,"experimentAnswers.question.answers.text":"Nonsmokers","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":102,"experimentAnswers.answer.id":305,"experimentAnswers.answer.text":"No marijuana use","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":102},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5802,"experimentAnswers.text":null,"experimentAnswers.answerId":200,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":101,"experimentAnswers.question.id":101,"experimentAnswers.question.text":"Demographic characteristics","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":203,"experimentAnswers.question.answers.text":"Patients","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":101,"experimentAnswers.answer.id":200,"experimentAnswers.answer.text":"Males","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":101},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5803,"experimentAnswers.text":null,"experimentAnswers.answerId":202,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":101,"experimentAnswers.question.id":101,"experimentAnswers.question.text":"Demographic characteristics","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":203,"experimentAnswers.question.answers.text":"Patients","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":101,"experimentAnswers.answer.id":202,"experimentAnswers.answer.text":"Healthy volunteers","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":101},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5802,"experimentAnswers.text":null,"experimentAnswers.answerId":200,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":101,"experimentAnswers.question.id":101,"experimentAnswers.question.text":"Demographic characteristics","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":202,"experimentAnswers.question.answers.text":"Healthy volunteers","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":101,"experimentAnswers.answer.id":200,"experimentAnswers.answer.text":"Males","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":101},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5803,"experimentAnswers.text":null,"experimentAnswers.answerId":202,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":101,"experimentAnswers.question.id":101,"experimentAnswers.question.text":"Demographic characteristics","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":202,"experimentAnswers.question.answers.text":"Healthy volunteers","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":101,"experimentAnswers.answer.id":202,"experimentAnswers.answer.text":"Healthy volunteers","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":101},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5802,"experimentAnswers.text":null,"experimentAnswers.answerId":200,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":101,"experimentAnswers.question.id":101,"experimentAnswers.question.text":"Demographic characteristics","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":201,"experimentAnswers.question.answers.text":"Females","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":101,"experimentAnswers.answer.id":200,"experimentAnswers.answer.text":"Males","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":101},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5803,"experimentAnswers.text":null,"experimentAnswers.answerId":202,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":101,"experimentAnswers.question.id":101,"experimentAnswers.question.text":"Demographic characteristics","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":201,"experimentAnswers.question.answers.text":"Females","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":101,"experimentAnswers.answer.id":202,"experimentAnswers.answer.text":"Healthy volunteers","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":101},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5802,"experimentAnswers.text":null,"experimentAnswers.answerId":200,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":101,"experimentAnswers.question.id":101,"experimentAnswers.question.text":"Demographic characteristics","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":200,"experimentAnswers.question.answers.text":"Males","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":101,"experimentAnswers.answer.id":200,"experimentAnswers.answer.text":"Males","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":101},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5803,"experimentAnswers.text":null,"experimentAnswers.answerId":202,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":101,"experimentAnswers.question.id":101,"experimentAnswers.question.text":"Demographic characteristics","experimentAnswers.question.required":true,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":200,"experimentAnswers.question.answers.text":"Males","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":null,"experimentAnswers.question.answers.questionId":101,"experimentAnswers.answer.id":202,"experimentAnswers.answer.text":"Healthy volunteers","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":null,"experimentAnswers.answer.questionId":101},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":703,"experimentAnswers.question.answers.text":"Ear and labyrinth disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35400000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":703,"experimentAnswers.question.answers.text":"Ear and labyrinth disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35400000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":703,"experimentAnswers.question.answers.text":"Ear and labyrinth disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35400000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":703,"experimentAnswers.question.answers.text":"Ear and labyrinth disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35400000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":703,"experimentAnswers.question.answers.text":"Ear and labyrinth disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35400000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":703,"experimentAnswers.question.answers.text":"Ear and labyrinth disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35400000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":702,"experimentAnswers.question.answers.text":"Congenital, familial and genetic disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35300000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":702,"experimentAnswers.question.answers.text":"Congenital, familial and genetic disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35300000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":702,"experimentAnswers.question.answers.text":"Congenital, familial and genetic disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35300000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":702,"experimentAnswers.question.answers.text":"Congenital, familial and genetic disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35300000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":702,"experimentAnswers.question.answers.text":"Congenital, familial and genetic disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35300000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":702,"experimentAnswers.question.answers.text":"Congenital, familial and genetic disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35300000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5823,"experimentAnswers.text":null,"experimentAnswers.answerId":711,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":701,"experimentAnswers.question.answers.text":"Cardiac disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35200000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":711,"experimentAnswers.answer.text":"Injury, poisoning and procedural complications","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36200000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5824,"experimentAnswers.text":null,"experimentAnswers.answerId":713,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":701,"experimentAnswers.question.answers.text":"Cardiac disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35200000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":713,"experimentAnswers.answer.text":"Metabolism and nutrition disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36400000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5825,"experimentAnswers.text":null,"experimentAnswers.answerId":716,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":701,"experimentAnswers.question.answers.text":"Cardiac disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35200000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":716,"experimentAnswers.answer.text":"Nervous system disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36700000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5822,"experimentAnswers.text":null,"experimentAnswers.answerId":707,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":701,"experimentAnswers.question.answers.text":"Cardiac disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35200000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":707,"experimentAnswers.answer.text":"General disorders and administration site conditions","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":35800000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5826,"experimentAnswers.text":null,"experimentAnswers.answerId":718,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":701,"experimentAnswers.question.answers.text":"Cardiac disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35200000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":718,"experimentAnswers.answer.text":"Psychiatric disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":36900000,"experimentAnswers.answer.questionId":128},{"id":278,"uid":"NPDI-wx2mcg","name":"Plasma Concentration of CBD when Fed","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Table 1)","experimentalConditionsComment":null,"resultsComment":"Results from Table 1","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":null,"cytochromeB5Id":null,"studyId":60,"experimentTypeId":8,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType.id":8,"experimentType.name":"In Vivo Pharmacokinetics","experimentType.isInVitro":false,"experimentType.isTransporter":false,"experimentType.isEnzyme":false,"experimentType.purl":"http://purl.obolibrary.org/obo/DIDEO_00000075","objectCompound.id":null,"objectCompound.name":null,"objectCompound.unii":null,"objectCompound.inChIKey":null,"objectCompound.publicDescription":null,"objectCompound.internalComment":null,"objectCompound.conceptId":null,"objectCompound.enantiomerOfId":null,"objectCompound.concept.conceptId":null,"objectCompound.concept.conceptName":null,"objectCompound.concept.domainId":null,"objectCompound.concept.vocabularyId":null,"objectCompound.concept.conceptClassId":null,"objectCompound.concept.standardConcept":null,"objectCompound.concept.conceptCode":null,"objectCompound.concept.validStartDate":null,"objectCompound.concept.validEndDate":null,"objectCompound.concept.invalid_reason":null,"precipitantCompound.id":null,"precipitantCompound.name":null,"precipitantCompound.unii":null,"precipitantCompound.inChIKey":null,"precipitantCompound.publicDescription":null,"precipitantCompound.internalComment":null,"precipitantCompound.conceptId":null,"precipitantCompound.enantiomerOfId":null,"precipitantCompound.concept.conceptId":null,"precipitantCompound.concept.conceptName":null,"precipitantCompound.concept.domainId":null,"precipitantCompound.concept.vocabularyId":null,"precipitantCompound.concept.conceptClassId":null,"precipitantCompound.concept.standardConcept":null,"precipitantCompound.concept.conceptCode":null,"precipitantCompound.concept.validStartDate":null,"precipitantCompound.concept.validEndDate":null,"precipitantCompound.concept.invalid_reason":null,"objectMetaboliteCompound.id":null,"objectMetaboliteCompound.name":null,"objectMetaboliteCompound.unii":null,"objectMetaboliteCompound.inChIKey":null,"objectMetaboliteCompound.publicDescription":null,"objectMetaboliteCompound.internalComment":null,"objectMetaboliteCompound.conceptId":null,"objectMetaboliteCompound.enantiomerOfId":null,"objectMetaboliteCompound.concept.conceptId":null,"objectMetaboliteCompound.concept.conceptName":null,"objectMetaboliteCompound.concept.domainId":null,"objectMetaboliteCompound.concept.vocabularyId":null,"objectMetaboliteCompound.concept.conceptClassId":null,"objectMetaboliteCompound.concept.standardConcept":null,"objectMetaboliteCompound.concept.conceptCode":null,"objectMetaboliteCompound.concept.validStartDate":null,"objectMetaboliteCompound.concept.validEndDate":null,"objectMetaboliteCompound.concept.invalid_reason":null,"enzymes.id":null,"enzymes.name":null,"enzymes.conceptId":null,"enzymes.experiment_enzyme_xref.enzymeId":null,"enzymes.experiment_enzyme_xref.experimentId":null,"transporters.id":null,"transporters.name":null,"transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":null,"transporters.experiment_transporter_xref.transporterId":null,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":60,"study.uid":"NPDI-UXOaUA","study.name":"A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray","study.napdiIdentifier":"PMID: 23052407","study.overallSummary":"Purpose To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/can- nabidiol (CBD) spray, an endocannabinoid system modula- tor, when administered to healthy male subjects.
Methods Twelve subjects took part in this fed–fasted cross- over study and received a single dose of THC/CBD spray (4 sprays 0 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time- points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
Results Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80– 14.91 ng/ml) and lower in 5 subjects (2.81–3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97– 9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0–t), AUC(0–inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2–2.5 h. Only mild adverse events were reported.
Conclusions The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.","study.pubmedId":23052407,"study.embaseId":null,"study.croIdentifier":"GW Pharma Ltd","study.croInformation":"GW Pharma Ltd","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis sativa","study.naturalProduct.name":"Cannabis","study.naturalProduct.itis":null,"study.naturalProduct.srs":"4495dd37-943e-434d-bf30-ea9172d543c8","study.naturalProduct.source_id":"","study.naturalProduct.conceptId":null,"study.naturalProduct.concept.conceptId":null,"study.naturalProduct.concept.conceptName":null,"study.naturalProduct.concept.domainId":null,"study.naturalProduct.concept.vocabularyId":null,"study.naturalProduct.concept.conceptClassId":null,"study.naturalProduct.concept.standardConcept":null,"study.naturalProduct.concept.conceptCode":null,"study.naturalProduct.concept.validStartDate":null,"study.naturalProduct.concept.validEndDate":null,"study.naturalProduct.concept.invalid_reason":null,"study.compound.id":null,"study.compound.name":null,"study.compound.unii":null,"study.compound.inChIKey":null,"study.compound.publicDescription":null,"study.compound.internalComment":null,"study.compound.conceptId":null,"study.compound.enantiomerOfId":null,"study.studySourceType.id":1,"study.studySourceType.name":"Published report","testSystem.id":null,"testSystem.name":null,"testSystem.sortOrder":null,"testSystem.conceptId":null,"testSystem.categoryId":null,"testSystem.category.id":null,"testSystem.category.name":null,"testSystem.category.sortOrder":null,"testSystem.category.requiresCytochromeB5":null,"cytochromeB5.id":null,"cytochromeB5.name":null,"cytochromeB5.sortOrder":null,"cytochromeB5.conceptId":null,"controlDataExperiment.id":null,"controlDataExperiment.uid":null,"controlDataExperiment.name":null,"controlDataExperiment.overallEffect":null,"controlDataExperiment.isControlData":null,"controlDataExperiment.isIc50Shift":null,"controlDataExperiment.croCutoff":null,"controlDataExperiment.croIdentifier":null,"controlDataExperiment.comment":null,"controlDataExperiment.experimentalConditionsComment":null,"controlDataExperiment.resultsComment":null,"controlDataExperiment.internalComment":null,"controlDataExperiment.objectCompoundId":null,"controlDataExperiment.objectMetaboliteCompoundId":null,"controlDataExperiment.precipitantCompoundId":null,"controlDataExperiment.cytochromeB5Id":null,"controlDataExperiment.studyId":null,"controlDataExperiment.experimentTypeId":null,"controlDataExperiment.testSystemId":null,"controlDataExperiment.ic50ShiftExperimentId":null,"controlDataExperiment.controlDataExperimentId":null,"controlDataExperiment.controlDataForExperimentId":null,"controlDataExperiment.naturalProductSampleId":null,"controlDataExperiment.experimentType.id":null,"controlDataExperiment.experimentType.name":null,"controlDataExperiment.experimentType.isInVitro":null,"controlDataExperiment.experimentType.isTransporter":null,"controlDataExperiment.experimentType.isEnzyme":null,"controlDataExperiment.experimentType.purl":null,"controlDataExperiment.objectCompound.id":null,"controlDataExperiment.objectCompound.name":null,"controlDataExperiment.objectCompound.unii":null,"controlDataExperiment.objectCompound.inChIKey":null,"controlDataExperiment.objectCompound.publicDescription":null,"controlDataExperiment.objectCompound.internalComment":null,"controlDataExperiment.objectCompound.conceptId":null,"controlDataExperiment.objectCompound.enantiomerOfId":null,"controlDataExperiment.precipitantCompound.id":null,"controlDataExperiment.precipitantCompound.name":null,"controlDataExperiment.precipitantCompound.unii":null,"controlDataExperiment.precipitantCompound.inChIKey":null,"controlDataExperiment.precipitantCompound.publicDescription":null,"controlDataExperiment.precipitantCompound.internalComment":null,"controlDataExperiment.precipitantCompound.conceptId":null,"controlDataExperiment.precipitantCompound.enantiomerOfId":null,"controlDataExperiment.objectMetaboliteCompound.id":null,"controlDataExperiment.objectMetaboliteCompound.name":null,"controlDataExperiment.objectMetaboliteCompound.unii":null,"controlDataExperiment.objectMetaboliteCompound.inChIKey":null,"controlDataExperiment.objectMetaboliteCompound.publicDescriptio":null,"controlDataExperiment.objectMetaboliteCompound.internalComment":null,"controlDataExperiment.objectMetaboliteCompound.conceptId":null,"controlDataExperiment.objectMetaboliteCompound.enantiomerOfId":null,"controlDataExperiment.enzymes.id":null,"controlDataExperiment.enzymes.name":null,"controlDataExperiment.enzymes.conceptId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.enzymeId":null,"controlDataExperiment.enzymes.experiment_enzyme_xref.experiment":null,"controlDataExperiment.transporters.id":null,"controlDataExperiment.transporters.name":null,"controlDataExperiment.transporters.conceptId":null,"controlDataExperiment.transporters.experiment_transporter_xref.":null,"controlDataExperiment.quantifiedMetabolites.id":null,"controlDataExperiment.quantifiedMetabolites.name":null,"controlDataExperiment.quantifiedMetabolites.unii":null,"controlDataExperiment.quantifiedMetabolites.inChIKey":null,"controlDataExperiment.quantifiedMetabolites.publicDescription":null,"controlDataExperiment.quantifiedMetabolites.internalComment":null,"controlDataExperiment.quantifiedMetabolites.conceptId":null,"controlDataExperiment.quantifiedMetabolites.enantiomerOfId":null,"controlDataExperiment.quantifiedMetabolites.experiment_quantifi":null,"experimentAnswers.id":5827,"experimentAnswers.text":null,"experimentAnswers.answerId":721,"experimentAnswers.experimentId":278,"experimentAnswers.questionId":128,"experimentAnswers.question.id":128,"experimentAnswers.question.text":"Adverse event classes","experimentAnswers.question.required":false,"experimentAnswers.question.maxAnswers":100,"experimentAnswers.question.type":null,"experimentAnswers.question.conceptId":null,"experimentAnswers.question.answers.id":701,"experimentAnswers.question.answers.text":"Cardiac disorders","experimentAnswers.question.answers.sortOrder":null,"experimentAnswers.question.answers.conceptId":35200000,"experimentAnswers.question.answers.questionId":128,"experimentAnswers.answer.id":721,"experimentAnswers.answer.text":"Respiratory, thoracic and mediastinal disorders","experimentAnswers.answer.sortOrder":null,"experimentAnswers.answer.conceptId":37200000,"experimentAnswers.answer.questionId":128}]