The consequences of 3,4-methylenedioxymethamphetamine induced CYP2D6 inhibition in humans

Brian O'Mathúna, Magi Farré, Amin Rostami-Hodjegan, Jiansong Yang, Elisabet Cuyàs, Marta Torrens, Ricardo Pardo, Sergio Abanades, Silvana Maluf, Geoffrey T. Tucker, Rafael De La Torre

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49 Citations (Scopus)


3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a widely abused substituted amphetamine. MDMA is predominantly O-demethylenated in humans by cytochrome P450 isoforms 2D6 and 1A2 (CYP2D6 and CYP CYP1A2, respectively). MDMA is also a mechanism-based inhibitor of CYP2D6. A controlled clinical trial was conducted in 15 healthy male subjects whereby a probe drug, dextromethorphan (DEX), was administered after an oral dose of 1.5 mg/kg MDMA. The pharmacokinetics of DEX and its metabolites were used to evaluate changes in CYP2D6 activity. The urinary metabolic ratio of DEX and dextrorphan was used to calculate a recovery half-life of CYP2D6. After MDMA, DEX Cmax and area under the curve increased approximately 10-fold with corresponding decreases in dextrorphan pharmacokinetic parameters. The metabolic ratio increased almost 100-fold from 0.0061 ± 0.0056 to 0.4322 ± 0.2848 after MDMA administration, with 67% of the subjects having a value greater than the antimode of 0.3 for assigning the poor metabolizer phenotype. CYP2D6 activity recovered after 10 days with a recovery half-life of 46.6 hours. In addition to the possible long-term serotonergic effects of MDMA, users must be warned of the consequences of such an inhibition. Copyright © 2008 by Lippincott Williams & Wilkins.
Original languageEnglish
Pages (from-to)525-531
JournalJournal of Clinical Psychopharmacology
Issue number5
Publication statusPublished - 1 Jan 2008


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