-Methylenedioxymethamphetamine (MDMA, Ecstasy) Induced Changes in Drug Metabolism: Gender and Genetic Polymorphisms

Human Study of the Metabolic Changes Induced by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) in the Metabolism of Dextromethorphan and Caffeine

The purpose of this study are:

1. to evaluate the involvement of CYP2D6, CYP3A4 and CYP1A2 (through dextromethorphan and caffeine challenges), and catechol-O-methyltransferase (COMT)in MDMA metabolism
2. to evaluate gender differences in the human pharmacology of MDMA
3. to study the influence of some genetic polymorphisms (CYP2D6, COMT, SERT) in the effects and pharmacokinetics of MDMA.

Inclusion Criteria:

• Healthy male and female adults, the recreational use of MDMA on at least ten occasions (two in the previous year), and the EM phenotype for CYP2D6 activity determined using dextromethorphan as a selective probe drug.
• Women had to present a regular menstrual cycle and not take oral contraceptives.

Exclusion Criteria:

• Daily consumption >20 cigarettes and >4 standard units of ethanol in men (>2 in women)
• Regular ingestion of medication in the month preceding the study
• Presence of major psychiatric disorders
• History of abuse or drug dependence (except for nicotine dependence)
• Psychiatric adverse reactions after MDMA consumption.