-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.

Study Overview

• Status: Completed
• Conditions: Metabolism; Interaction
• Intervention / Treatment: Drug: MDMA

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • IMIM-Hospital del Mar (Institut de Recerca Hospital del Mar)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MDMA; One single dose of MDMA (1.5 mg/kg; range 75-100 mg)	Drug: MDMA; One single dose of MDMA ( 1.5 mg/kg; range: 75-100 mg); Other Names: Ecstasy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Parc de Salut Mar
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Magí Farre, PhD, IMIM-Hospital del Mar (Institut de Recerca Hospital del Mar)

Publications and helpful links

General Publications

• Yubero-Lahoz S, Pardo R, Farre M, O'Mahony B, Torrens M, Mustata C, Perez-Mana C, Carbo ML, de la Torre R. Sex differences in 3,4-methylenedioxymethamphetamine (MDMA; ecstasy)-induced cytochrome P450 2D6 inhibition in humans. Clin Pharmacokinet. 2011 May;50(5):319-29. doi: 10.2165/11584550-000000000-00000.
• O'Mathuna B, Farre M, Rostami-Hodjegan A, Yang J, Cuyas E, Torrens M, Pardo R, Abanades S, Maluf S, Tucker GT, de la Torre R. The consequences of 3,4-methylenedioxymethamphetamine induced CYP2D6 inhibition in humans. J Clin Psychopharmacol. 2008 Oct;28(5):523-9. doi: 10.1097/JCP.0b013e318184ff6e.
• Pardo-Lozano R, Farre M, Yubero-Lahoz S, O'Mathuna B, Torrens M, Mustata C, Perez-Mana C, Langohr K, Cuyas E, Carbo Ml, de la Torre R. Clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"): the influence of gender and genetics (CYP2D6, COMT, 5-HTT). PLoS One. 2012;7(10):e47599. doi: 10.1371/journal.pone.0047599. Epub 2012 Oct 24.

Study record dates

Study Major Dates

• Study Start: May 1, 2003
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: September 27, 2011
• First Submitted That Met QC Criteria: October 5, 2011
• First Posted (Estimate): October 6, 2011

Study Record Updates

• Last Update Posted (Estimate): October 6, 2011
• Last Update Submitted That Met QC Criteria: October 5, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: pharmacokinetics,; pharmacodynamics,; MDMA,; CYP2D6, COMT,; SERT, 5-HTTLPR, gender,; dextromethorphan,; caffeine.
• Other Study ID Numbers: IMIMFTCL/MDMA/6; AEMPS no.04-0013 (Other Identifier: Spanish Medicines Agency (identification number)); 5R01DA017987 (U.S. NIH Grant/Contract)