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

Study Overview
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Brief Summary
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The purpose of this study are: to evaluate the involvement of CYP2D6, CYP3A4 and CYP1A2 (through dextromethorphan and caffeine challenges), and catechol-O-methyltransferase (COMT)in MDMA metabolism to evaluate gender differences in the human pharmacology of MDMA to study the influence of some genetic polymorphisms (CYP2D6, COMT, SERT) in the effects and pharmacokinetics of MDMA.

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

Conditions
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Metabolism, Interaction

Intervention / Treatment
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* Drug: MDMA


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MDMA<br>One single dose of MDMA (1.5 mg/kg; range 75-100 mg) | Drug: MDMA<br>* One single dose of MDMA ( 1.5 mg/kg; range: 75-100 mg)<br>* Other names: Ecstasy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of dextromethorphan in plasma and urine. | Blood samples and urine to determine dextromethorphan and dextrorphan concentrations until 240h. | 240 hours after MDMA dosing. | 
| Concentrations of caffeine in plasma and urine. | Blood samples and urine to determine caffeine and theobromine concentrations until 240h. | 24 hours after MDMA dosing. | 
| Concentrations of MDMA and metabolites (influence of gender) | Determination of MDMA and metabolites concentrations in plasma and urine during 48h. Influence of gender male/female. | 48h after MDMA administration. | 
| Concentrations of MDMA and metabolites (influence of genetics) | Determination of MDMA and metabolites concentrations in plasma and urine during 48h. Influence of gene polymorphisms of CYP2D6, CYP3A4, COMT, SERT. | 48h after MDMA administration. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of MDMA on physiological response. | Effects of MDMA on blood preassure, heart rate, temperature, pupil diameter, esophoria. Influence of gender and genetic polymorphisms. | 24h | 
| Effects of MDMA on physiological response. | Effects of MDMA on subjective effects (feelings of intoxication, euphoria, bad effects etc) and psychological tests (VESSPA, ARCI). Influence of gender and genetic polymorphisms. | 24h | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDMA,, pharmacokinetics,, pharmacodynamics,, CYP2D6, COMT,, SERT, 5-HTTLPR, gender,, dextromethorphan,, caffeine.