Kratom (Mitragyna speciosa)

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Latin Binomial: Mitragyna speciosa
Common Names: Kratom and Kratum

Natural Product Information From GSRS

Mitragyna speciosa

Resource	Identifier

= Induction
= Inhibition
= No overall effect

Published in vitro enzyme experiments

	mitragynine	7-hydroxymitragynine	ketamine	buprenorphine	diclofenac	sulfaphenazole	quinidine	ketoconazole	methanolic extract of kratom	alpha-naphthoflavone	montelukast	(s)-(+)-n-3-benzylnirvanol	speciogynine	speciociliatine	corynantheidine	paynantheine
CYP2D6
CYP3A4
CYP1A2
CYP2C19
UGT
UGT1A1
UGT2B7
CYP2C9
CYP3A
CYP2C8
CYP3A5

Published in vitro transporter experiments

	mitragynine	rifampicin	quinidine	7-hydroxymitragynine
P-gp (ABCB1)

Chemical characterization

	mitragynine	7-hydroxymitragynine	rotundifoline
Characterization of Kratom material	22.7 ± 3.3 mg/g sample	0.567 ± 0.04 mg/g sample	0.41 ± 0.024 mg/g sample

Published clinical experiments

Inhibition detected

midazolam

No overall effect

dextromethorphan

Metabolomics

51 Samples

6 principle components (97.00999999999999% of variability)

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2-D 3-D

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Case Reports

Drugs involved in Case Reports 1

quetiapine

Experiments

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ID	Subject of Study	Study Name	Name	Type	Overall Effect	Enzymes	Transporters	Object	Object Metabolite	Precipitant
NPDI--fog0A	Kratom (Mitragyna speciosa)	Clinical Assessment of the Drug Interaction Potential of the Psychotropic Natural Product Kratom	kratom tea - dextromethorphan interaction clinical NPDI study	In Vivo Interaction	negative — No Effect (based on bioequivalence limits)	CYP2D6		dextromethorphan		water extract of kratom
NPDI--jKvig	Kratom (Mitragyna speciosa)	Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations	IC50 shift determination for mitragynine towards CYP2D6 activity in HLM without NADPH	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	CYP2D6		dextromethorphan	dextrorphan	mitragynine
NPDI-0hNq0Q	Kratom (Mitragyna speciosa)	Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids	Weak Inhibition of Mitragynine for CYP2C9	In Vitro Enzyme Inhibition	negative — In Vitro Enzyme Negligible Inhibition	CYP2C9		diclofenac	4'-hydroxydiclofenac	mitragynine
NPDI-17YRkg	Kratom (Mitragyna speciosa)	Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids	Inhibition of Mitragynine for CYP2D6	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	CYP2D6		dextromethorphan	dextrorphan	mitragynine
NPDI-1Cjyxg	Kratom (Mitragyna speciosa)	Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids	Weak Inhibition of Cornantheidine for CYP1A2	In Vitro Enzyme Inhibition	negative — In Vitro Enzyme Negligible Inhibition	CYP1A2		phenacetin	acetaminophen	corynantheidine
NPDI-1tFkCA	Kratom (Mitragyna speciosa)	Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities	Inhibition of CYP2C9 by mitragynine	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	CYP2C9		6’deoxyluciferin (luciferin h)	luciferin	mitragynine
NPDI-1vxnrQ	Kratom (Mitragyna speciosa)	Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids	Weak Inhibition of 7-hydroxymitragynine for CYP1A2	In Vitro Enzyme Inhibition	negative — In Vitro Enzyme Negligible Inhibition	CYP1A2		phenacetin	acetaminophen	7-hydroxymitragynine
NPDI-2HCqSQ	Kratom (Mitragyna speciosa)	Evaluation of In Vitro Absorption, Distribution, Metabolism, and Excretion (ADME) Properties of Mitragynine, 7-Hydroxymitragynine, and Mitraphylline	Mitraphylline p-gp transport kinetics MDCK	In Vitro Transporter Kinetics	positive — In Vitro Transport		P-gp (ABCB1)	mitraphylline
NPDI-2seH4Q	Kratom (Mitragyna speciosa)	Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids	Weak Inhibition of Speciociliatine for CYP3A4/5	In Vitro Enzyme Inhibition	negative — In Vitro Enzyme Negligible Inhibition	CYP3A4 CYP3A5		testosterone	6beta-hydroxytestosterone	speciociliatine
NPDI-2VLnZA	Kratom (Mitragyna speciosa)	Evaluation of In Vitro Absorption, Distribution, Metabolism, and Excretion (ADME) Properties of Mitragynine, 7-Hydroxymitragynine, and Mitraphylline	Mitragynine P-gp transport activity	In Vitro Transporter Kinetics	negative — No In Vitro Transport Activity		P-gp (ABCB1)	mitragynine
NPDI-38uQKg	Kratom (Mitragyna speciosa)	Metabolite profiling and identification of enzymes responsible for the metabolism of mitragynine, the major alkaloid of Mitragyna speciosa (kratom)	Mitragynine metabolism and metabolite formation	In Vitro Enzyme Screen	positive — In Vitro Detectable Metabolism	CYP3A4		mitragynine	7-hydroxymitragynine
NPDI-3C6gmg	Kratom (Mitragyna speciosa)	Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms	Negligible inhibition of UGT2B7 by 7-hydroxymitragynine	In Vitro Enzyme Inhibition	negative — In Vitro Enzyme Negligible Inhibition	UGT2B7		4-methylumbelliferone	4-methylumbelliferone glucuronide	7-hydroxymitragynine
NPDI-3eovVg	Kratom (Mitragyna speciosa)	Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms	Negligible inhibition of UGT1A1 by buprenorphine	In Vitro Enzyme Inhibition	negative — In Vitro Enzyme Negligible Inhibition	UGT1A1		4-methylumbelliferone	4-methylumbelliferone glucuronide	buprenorphine
NPDI-4_m2Gw	Kratom (Mitragyna speciosa)	Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms	Inhibition of UGT1A1 by diclofenac	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	UGT1A1		4-methylumbelliferone	4-methylumbelliferone glucuronide	diclofenac
NPDI-4_UdSg	Kratom (Mitragyna speciosa)	Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations	IC50 shift determination for mitragynine towards CYP3A activity in HLM with NADPH	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	CYP3A		midazolam	1'-hydroxymidazolam	mitragynine
NPDI-4AITQg	Kratom (Mitragyna speciosa)	Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids	Control Positive Inhibition for CYP2D6	In Vitro Enzyme Inhibition (Control experiment)	positive — In Vitro Enzyme Inhibition	CYP2D6		dextromethorphan	dextrorphan	quinidine
NPDI-4do0FA	Kratom (Mitragyna speciosa)	Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms	Inhibition of UGT1A1 by 7-hydroxymitragynine	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	UGT1A1		4-methylumbelliferone	4-methylumbelliferone glucuronide	7-hydroxymitragynine
NPDI-4HfEdA	Kratom (Mitragyna speciosa)	Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids	Inhibition of Paynantheine for CYP2C9	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	CYP2C9		diclofenac	4'-hydroxydiclofenac	paynantheine
NPDI-4k7d3A	Kratom (Mitragyna speciosa)	The inhibitory effects of mitragynine on P-glycoprotein in vitro	Induction of P-gp protein expression by 1 µM rifampicin	In Vitro Transporter Induction	positive — In Vitro Transporter Induction		P-gp (ABCB1)			rifampicin
NPDI-515DHw	Kratom (Mitragyna speciosa)	Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations	Inhibition kinetics of CYP3A activity by mitragynine in HLM	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	CYP3A		midazolam	1'-hydroxymidazolam	mitragynine
NPDI-5LuVNQ	Kratom (Mitragyna speciosa)	Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids	Control Positive Inhibition for CYP1A2	In Vitro Enzyme Inhibition (Control experiment)	positive — In Vitro Enzyme Inhibition	CYP1A2		phenacetin	acetaminophen	alpha-naphthoflavone
NPDI-5VhYlA	Kratom (Mitragyna speciosa)	Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms	Negligible inhibition of UGT1A1 by mitragynine	In Vitro Enzyme Inhibition	negative — In Vitro Enzyme Negligible Inhibition	UGT1A1		4-methylumbelliferone	4-methylumbelliferone glucuronide	mitragynine
NPDI-7-Gg-g	Kratom (Mitragyna speciosa)	Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations	Screening of kratom extracts as inhibitors of CYP3A activity in HLM	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	CYP3A		midazolam	1'-hydroxymidazolam	methanolic extract of kratom
NPDI-71pBaQ	Kratom (Mitragyna speciosa)	Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations	Screening of kratom extracts as inhibitors of CYP2C9 activity in HLM	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	CYP2C9		diclofenac	4'-hydroxydiclofenac	methanolic extract of kratom
NPDI-79TG7g	Kratom (Mitragyna speciosa)	Evaluation of selected Malaysian medicinal plants on phase I drug metabolizing enzymes, CYP2C9, CYP2D6 and CYP3A4 activities in vitro	POS. CONTROL: Inhibition of CYP3A4 by ketoconazole	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	CYP3A4		luciferin 6’benzyl ether (luciferin-be)	luciferin	ketoconazole
NPDI-7PU97Q	Kratom (Mitragyna speciosa)	Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids	Inhibition of Corynantheidine for CYP3A4/5	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	CYP3A4 CYP3A5		midazolam	1'-hydroxymidazolam	corynantheidine
NPDI-8GmUTQ	Kratom (Mitragyna speciosa)	The inhibitory effects of mitragynine on P-glycoprotein in vitro	Induction of P-gp protein expression by 10 µM rifampicin	In Vitro Transporter Induction	positive — In Vitro Transporter Induction		P-gp (ABCB1)			rifampicin
NPDI-9spGvg	Kratom (Mitragyna speciosa)	Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms	Negligible inhibition of UGT2B7 by mitragynine	In Vitro Enzyme Inhibition	negative — In Vitro Enzyme Negligible Inhibition	UGT2B7		4-methylumbelliferone	4-methylumbelliferone glucuronide	mitragynine
NPDI-9xzv_Q	Kratom (Mitragyna speciosa)	Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids	Control Positive Inhibition for CYP3A4/5	In Vitro Enzyme Inhibition (Control experiment)	positive — In Vitro Enzyme Inhibition	CYP3A4 CYP3A5		testosterone	6beta-hydroxytestosterone	ketoconazole
NPDI-_5ld1Q	Kratom (Mitragyna speciosa)	Evaluation of In Vitro Absorption, Distribution, Metabolism, and Excretion (ADME) Properties of Mitragynine, 7-Hydroxymitragynine, and Mitraphylline	7-Hydroxymitragynine P-gp Inhibition	In Vitro Transporter Inhibition	positive — In Vitro Transporter Inhibition		P-gp (ABCB1)	calcein-am		7-hydroxymitragynine
NPDI-_MFsyA	Kratom (Mitragyna speciosa)	Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids	Weak Inhibition of Speciogynine for CYP1A2	In Vitro Enzyme Inhibition	negative — In Vitro Enzyme Negligible Inhibition	CYP1A2		phenacetin	acetaminophen	speciogynine
NPDI-_PhwAA	Kratom (Mitragyna speciosa)	Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities	Inhibition of CYP2D6 by mitragynine	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	CYP2D6		ethylene glycol ester of luciferin 6’methyl ether (luciferin me-ege)	luciferin	mitragynine
NPDI-A66pwQ	Kratom (Mitragyna speciosa)	Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations	IC50 shift determination for mitragynine towards CYP3A activity in HIM with NADPH	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	CYP3A		midazolam	1'-hydroxymidazolam	mitragynine
NPDI-aGXuxA	Kratom (Mitragyna speciosa)	Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids	Weak Inhibition of Corynantheidine for CYP2C19	In Vitro Enzyme Inhibition	negative — In Vitro Enzyme Negligible Inhibition	CYP2C19		mephenytoin, (s)-	4-hydroxymephenytoin, (s)-	corynantheidine
NPDI-aNb3lw	Kratom (Mitragyna speciosa)	Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids	Weak Inhibition of Paynantheine for CYP3A4/5	In Vitro Enzyme Inhibition	negative — In Vitro Enzyme Negligible Inhibition	CYP3A4 CYP3A5		testosterone	6beta-hydroxytestosterone	paynantheine
NPDI-B_7tOA	Kratom (Mitragyna speciosa)	Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids	Weak Inhibition of Speciogynine for CYP2C8	In Vitro Enzyme Inhibition	negative — In Vitro Enzyme Negligible Inhibition	CYP2C8		amodiaquine	n-desethylamodiaquine	speciogynine
NPDI-BLzT_g	Kratom (Mitragyna speciosa)	Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids	Weak Inhibition of Mitragynine for CYP3A4/5	In Vitro Enzyme Inhibition	negative — In Vitro Enzyme Negligible Inhibition	CYP3A4 CYP3A5		testosterone	6beta-hydroxytestosterone	mitragynine
NPDI-bOmVTQ	Kratom (Mitragyna speciosa)	Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations	Screening of mitragynine as inhibitors of CYP2C9 activity in HLM	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	CYP2C9		diclofenac	4'-hydroxydiclofenac	mitragynine
NPDI-bX8XPA	Kratom (Mitragyna speciosa)	Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’- diphospho-glucuronosyltransferase isoforms	No inhibition of UGT2B7 by ketamine	In Vitro Enzyme Inhibition	negative — In Vitro Enzyme Negligible Inhibition	UGT2B7		4-methylumbelliferone	4-methylumbelliferone glucuronide	ketamine
NPDI-bXPXRQ	Kratom (Mitragyna speciosa)	Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids	Inhibition of Corynantheidine for CYP2C9	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	CYP2C9		diclofenac	4'-hydroxydiclofenac	corynantheidine
NPDI-c1a6PQ	Kratom (Mitragyna speciosa)	Clinical Pharmacokinetic Assessment of Kratom (Mitragyna speciosa), a Botanical Product with Opioid-like Effects, in Healthy Adult Participants	isopaynantheine	In Vivo Pharmacokinetics
NPDI-c_gPeA	Kratom (Mitragyna speciosa)	Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids	Inhibition of Mitragynine for CYP3A4/5	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	CYP3A4 CYP3A5		midazolam	1'-hydroxymidazolam	mitragynine
NPDI-cimaKA	Kratom (Mitragyna speciosa)	Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids	Weak Inhibition of 7-hydroxymitragynine for CYP2D6	In Vitro Enzyme Inhibition	negative — In Vitro Enzyme Negligible Inhibition	CYP2D6		dextromethorphan	dextrorphan	7-hydroxymitragynine
NPDI-cxxGnA	Kratom (Mitragyna speciosa)	The inhibitory effects of mitragynine on P-glycoprotein in vitro	Control P-gp digoxin transport	In Vitro Transporter Kinetics (Control experiment)	positive — In Vitro Transport		P-gp (ABCB1)	digoxin
NPDI-d-iKog	Kratom (Mitragyna speciosa)	Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities	POS. CONTROL: Inhibition of CYP3A4 by ketoconazole	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	CYP3A4		luciferin 6’benzyl ether (luciferin-be)	luciferin	ketoconazole
NPDI-d0noGQ	Kratom (Mitragyna speciosa)	Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities	POS. CONTROL: Inhibition of CYP2D6 by quinidine	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	CYP2D6		ethylene glycol ester of luciferin 6’methyl ether (luciferin me-ege)	luciferin	quinidine
NPDI-d5Gm3Q	Kratom (Mitragyna speciosa)	Evaluation of the Effects of Mitragyna speciosa Alkaloid Extract on Cytochrome P450 Enzymes Using a High Throughput Assay	Mitragynine inhibition of CYP2C19	In Vitro Enzyme Inhibition	positive — In Vitro Enzyme Inhibition	CYP2C19		3-cyano-7-ethoxycoumarin	3-cyano-7-hydroxycoumarin	mitragynine
NPDI-DEOq7g	Kratom (Mitragyna speciosa)	The inhibitory effects of mitragynine on P-glycoprotein in vitro	Down regulation of P-gp mRNA expression by 10 µM mitragynine	In Vitro Transporter Induction	positive — In Vitro Transporter Down Regulation		P-gp (ABCB1)			mitragynine
NPDI-Df2Xyw	Kratom (Mitragyna speciosa)	Evaluation of selected Malaysian medicinal plants on phase I drug metabolizing enzymes, CYP2C9, CYP2D6 and CYP3A4 activities in vitro	Negligible inhibition of CYP3A4 by M. speciosa methanolic extract	In Vitro Enzyme Inhibition	negative — In Vitro Enzyme Negligible Inhibition	CYP3A4		luciferin 6’benzyl ether (luciferin-be)	luciferin	methanolic extract of kratom
NPDI-DLH-JQ	Kratom (Mitragyna speciosa)	Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids	Weak Inhibition of 7-hydroxymitragynine for CYP2C9	In Vitro Enzyme Inhibition	negative — In Vitro Enzyme Negligible Inhibition	CYP2C9		diclofenac	4'-hydroxydiclofenac	7-hydroxymitragynine

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