Pharmacogenetics of ecstasy: CYP1A2, CYP2C19, and CYP2B6 polymorphisms moderate pharmacokinetics of MDMA in healthy subjects.
Patrick Vizeli, Yasmin Schmid, Katharina Prestin, Henriette E. Meyer zu Schwabedissen, Matthias E. Liechti
European Neuropsychopharmacology March 2017 DOI: 10.1016/j.euroneuro.2017.01.008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Pooled analysis of eight double-blind, placebo-controlled studies Peer reviewed |
|---|---|
| Sample size | 139 |
| Population | Healthy adults (69 male, 70 female) |
| Intervention | MDMA |
| Topics | MDMA |
| Keywords | 3,4-methylenedioxyamphetamine 3,4-methylenedioxymethamphetamine Cyp1a2 Cyp2b6 Cyp2c19 Pharmacokinetics |
| Key points | MDMA-to-MDA conversion was positively associated with genotypes conveying higher CYP2C19 or CYP2B6 activity. CYP2C19 poor metabolizers showed greater cardiovascular responses to MDMA than other CYP2C19 genotypes, and tobacco smokers with the inducible CYP1A2 rs762551 A/A genotype had higher peak MDA concentrations than C-allele carriers. The authors conclude that CYP2C19, CYP2B6, and CYP1A2 contribute to MDMA metabolism to MDA in humans and that CYP2C19 polymorphisms may moderate MDMA cardiovascular toxicity. |
Abstract
In vitro studies showed that CYP2C19, CYP2B6, and CYP1A2 contribute to the metabolism of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) to 3,4-methylenedioxyamphetamine (MDA). However, the role of genetic polymorphisms in CYP2C19, CYP2B6, and CYP1A2 in the metabolism of MDMA in humans is unknown. The effects of genetic variants in these CYP enzymes on the pharmacokinetics and pharmacodynamics of MDMA were characterized in 139 healthy subjects (69 male, 70 female) in a pooled analysis of eight double-blind, placebo-controlled studies. MDMA-MDA conversion was positively associated with genotypes known to convey higher CYP2C19 or CYP2B6 activities. Additionally, CYP2C19 poor metabolizers showed greater cardiovascular responses to MDMA compared with other CYP2C19 genotypes. Furthermore, the maximum concentration of MDA was higher in tobacco smokers that harbored the inducible CYP1A2 rs762551 A/A genotype compared with the non-inducible C-allele carriers. The findings indicate that CYP2C19, CYP2B6, and CYP1A2 contribute to the metabolism of MDMA to MDA in humans. Additionally, genetic polymorphisms in CYP2C19 may moderate the cardiovascular toxicity of MDMA.
Comparable studies
Other randomized controlled trials on MDMA, most cited first.
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