Clinical trial NCT01447472: -Methylenedioxymethamphetamine (MDMA, Ecstasy) Induced Changes in Drug Metabolism: Gender and Genetic Polymorphisms
Official title: Human Study of the Metabolic Changes Induced by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) in the Metabolism of Dextromethorphan and Caffeine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metabolism
Interaction
Keywords: MDMA,
pharmacokinetics,
pharmacodynamics,
CYP2D6, COMT,
SERT, 5-HTTLPR, gender,
dextromethorphan,
caffeine.
Lead sponsor: Parc de Salut Mar
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2011-10-06
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Concentrations of dextromethorphan in plasma and urine.
timeFrame: 240 hours after MDMA dosing.
measure: Concentrations of caffeine in plasma and urine.
timeFrame: 24 hours after MDMA dosing.
measure: Concentrations of MDMA and metabolites (influence of gender)
timeFrame: 48h after MDMA administration.
measure: Concentrations of MDMA and metabolites (influence of genetics)
timeFrame: 48h after MDMA administration.
Secondary outcomes:
measure: Effects of MDMA on physiological response.
timeFrame: 24h
measure: Effects of MDMA on physiological response.
timeFrame: 24h
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: IMIM-Hospital del Mar (Institut de Recerca Hospital del Mar)
Study officials:
affiliation: IMIM-Hospital del Mar (Institut de Recerca Hospital del Mar)
name: Magí Farre, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.