[{"id":58,"uid":"NPDI-gTt8Dw","name":"Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans","napdiIdentifier":"PMID: 25748562","overallSummary":"<div class=\"page\" title=\"Page 1\">\r\n<div class=\"section\">\r\n<div class=\"layoutArea\">\r\n<div class=\"column\">\r\n<p><strong>Objectives</strong> — Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects.</p>\r\n<p><strong>Methods</strong> — This double-blind, placebo-controlled cross-over study of CBD co-administered with intravenous fentanyl, was conducted at the Clinical Research Center in Mount Sinai Hospital, a tertiary care medical center in New York City. Participants were healthy volunteers aged 21–65 years with prior opioid exposure, regardless of route. Blood samples were obtained before and after 400 or 800 mg CBD pretreatment, followed by a single 0.5 (Session 1) or 1.0mcg/Kg (Session 2) intravenous fentanyl dose. The primary outcome was the Systematic Assessment for Treatment Emergent Events (SAFTEE) to assess safety and adverse effects. CBD peak plasma concentrations, time to reach peak plasma concentrations (tmax), and area under the curve (AUC) were measured.</p>\r\n</div>\r\n</div>\r\n</div>\r\n</div>\r\n<strong>Results </strong>— SAFTEE data were similar between groups without respiratory depression or cardiovascular complications during any test session. Following low dose CBD, tmax occurred at 3 and 1.5h (Sessions 1 and 2, respectively). Following high dose CBD, tmax occurred at 3 and 4h in Sessions 1 and 2, respectively. There were no significant differences in plasma CBD or cortisol (AUC p=NS) between sessions.<br /><br /><strong>Conclusions </strong>— CBD does not exacerbate adverse effects associated with intravenous fentanyl administration. Co-administration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse.","pubmedId":25748562,"embaseId":null,"croIdentifier":"The Icahn School of Medicine at Mount Sinai","croInformation":"The Icahn School of Medicine at Mount Sinai","dateStart":null,"dateEnd":null,"internalComment":null,"status":"published","compoundId":null,"naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","naturalProductSampleId":null,"studySourceTypeId":1,"naturalProduct":{"uid":"NP-0162af79-839e-40e2-af47-361c659061e9","binomial":"Cannabis sativa","name":"Cannabis","itis":null,"srs":"4495dd37-943e-434d-bf30-ea9172d543c8","source_id":"","conceptId":null},"compound":null,"studySourceType":{"id":1,"name":"Published report"},"experiments":[{"id":269,"uid":"NPDI-UlPhZQ","name":"Plasma CBD Concentrations","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"(Figure 2)","experimentalConditionsComment":"Biphasic with at least one week interim.<br />(Figure 1)","resultsComment":"Value reported estimated at 3 hours with 800 mg CBD (original value reported = ~170 µg/L)<br />With 400 mg CBD, Cmax mean ± SEM ~ 140 µg/L ± 20 µg/L<br />Values above converted to ng/mL.<br />CBD+placebo led to 0 µg/Lconcentration throughout the 8 hours collected.<br />(Figure 2)","internalComment":null,"objectCompoundId":116,"objectMetaboliteCompoundId":null,"precipitantCompoundId":115,"cytochromeB5Id":null,"studyId":58,"experimentTypeId":9,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":9,"name":"In Vivo Interaction","isInVitro":false,"isTransporter":false,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00000071"},"objectCompound":{"id":116,"name":"fentanyl","unii":null,"inChIKey":"PJMPHNIQZUBGLI-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":115,"name":"cannabidiol","unii":null,"inChIKey":"QHMBSVQNZZTUGM-ZWKOTPCHSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":null,"enzymes":[],"transporters":[],"quantifiedMetabolites":[]}]}]