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

Metabolism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01447472
• Other study ID #: IMIMFTCL/MDMA/6
• Secondary ID: AEMPS no.04-0013
• Status: Completed
• Phase: Phase 1
• First received: September 27, 2011
• Last updated: October 5, 2011
• Start date: May 2003
• Est. completion date: May 2011

Study information

• Verified date: October 2011
• Source: Parc de Salut Mar
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: May 2011
• Est. primary completion date: May 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Interaction
• Metabolism

Intervention

Drug:
• MDMA
One single dose of MDMA ( 1.5 mg/kg; range: 75-100 mg)

Locations

Country	Name	City	State
Spain	IMIM-Hospital del Mar (Institut de Recerca Hospital del Mar)	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Parc de Salut Mar	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

Spain, 

References & Publications (2)

O'Mathúna B, Farré M, Rostami-Hodjegan A, Yang J, Cuyàs 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) — View Citation

Yubero-Lahoz S, Pardo R, Farré M, O'Mahony B, Torrens M, Mustata C, Pérez-Mañá C, Carbó ML, de la Torre R. Sex differences in 3,4-methylenedioxymethamphetamine (MDMA; ecstasy)-induced cytochrome P450 2D6 inhibition in humans. Clin Pharmacokinet. 2011 May; — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentrations of dextromethorphan in plasma and urine.	Blood samples and urine to determine dextromethorphan and dextrorphan concentrations until 240h.	240 hours after MDMA dosing.	No
Primary	Concentrations of caffeine in plasma and urine.	Blood samples and urine to determine caffeine and theobromine concentrations until 240h.	24 hours after MDMA dosing.	No
Primary	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.	No
Primary	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.	No
Secondary	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	Yes
Secondary	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	No