Interaction Between Duloxetine and 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy)

MDMA

Brief Summary

The purpose of this study is to determinate the effect of a pre-treatment with the combined serotonin (5-HT) and norepinephrine (NE) transport blocker duloxetine on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"). The investigators hypothesize that duloxetine will attenuate the subjective and cardiovascular response to MDMA.

Intervention / Treatment

  • 3,4-methylenedioxymethamphetamine (DRUG)
    125 mg, single dose
  • Duloxetine (DRUG)
    120 mg two doses 12h and 2h before MDMA
  • Placebo (DRUG)
    capsules identical to MDMA or duloxetine

Condition or Disease

  • Mood Disorder
  • Substance-Related Disorders
  • Amphetamine-Related Disorders

Phase

  • Phase 1

    • Study Design

    Study type: INTERVENTIONAL
    Status: Completed
    Study results: No Results Available
    Age: 18 Years to 45 Years
    Enrollment: 16 (ACTUAL)
    Funded by: Other
    Allocation: Randomized
    Primary Purpose: Basic Science

    Masking

    DOUBLE:
    • Participant
    • Investigator

    Clinical Trial Dates

    Start date: Nov 01, 2009
    Primary Completion: May 01, 2010 ACTUAL
    Completion Date: May 01, 2010 ACTUAL
    Study First Posted: Oct 06, 2009 ESTIMATED
    Results First Posted: Aug 30, 2020
    Last Updated: Jan 24, 2013

    Sponsors / Collaborators

    Lead Sponsor: University Hospital, Basel, Switzerland
    Lead sponsor is responsible party
    Responsible Party: N/A

    Location

    Basel, Basel-Stadt, Switzerland

    3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is widely used by young people for its euphoric effects. MDMA releases serotonin (5-HT), norepinephrine (NE), and dopamine through an interaction with the corresponding presynaptic monoamine uptake transporter. 5-HT transport inhibitors block MDMA-induced 5-HT release in vitro or in animals and also attenuate the subjective and cardiovascular response to MDMA in humans. NE transport inhibitors similarly prevent the MDMA-induced release of NE in cell assays and attenuate behavioral effects of MDMA in animals. Effects of the NE transporter inhibitor reboxetine on the response to MDMA in humans are currently investigated. Here we suggest evaluating effects of pretreatment with the combined 5-HT and NE transport blocker duloxetine on the pharmacodynamics and pharmacokinetics of MDMA. The study will use a randomized double-blind cross-over design with four experimental sessions. Duloxetine (120 mg) or placebo will be administered 16 h and 4 h before the administration of MDMA (125 mg) or placebo to 16 healthy volunteers. Subjective and cardiovascular responses and plasma samples for pharmacokinetics will be repeatedly assessed throughout the experiments.

    Participant Groups

    • Cross-over within-subjects design with all treatment conditions tested in the same subject. This design has 1 arm but two (actually 4) treatment conditions in the same subject.

    Eligibility Criteria

    Sex: All
    Minimum Age: 18
    Maximum Age: 45
    Age Groups: Adult
    Healthy Volunteers: Yes

    Inclusion Criteria:

    * Sufficient understanding of the German language
    * Subjects understand the procedures and the risks associated with the study
    * Participants must be willing to adhere to the protocol and sign the consent form
    * Participants must be willing to refrain from taking illicit psychoactive substances during the study.
    * Participants must be willing to drink only alcohol-free liquids and no xanthine-containing liquids (such as coffee, black or green tea, red bull, chocolate) after midnight of the evening before the study session. Subjects must agree not to smoke tobacco for 1 h before and 4 hours after MDMA administration.
    * Participants must be willing not to drive a traffic vehicle in the evening of the study day.
    * Women of childbearing potential must have a negative pregnancy test at the beginning of the study and must agree to use an effective form of birth control. Pregnancy tests are repeated before each study session.
    * Body mass index: 18-25 kg/m2

    Exclusion Criteria:

    * Chronic or acute medical condition including clinically relevant abnormality in physical exam, laboratory values, or ECG. In particular: Hypertension (\>140/90 mmHg). Personal or first-grade history of seizures. Cardiac or neurological disorder.
    * Current or previous psychotic or affective disorder
    * Psychotic or affective disorder in first-degree relatives
    * Prior illicit drug use (except THC (Tetrahydrocannabinol)-containing products) more than 5 times or any time within the previous 2 months.
    * Pregnant or nursing women.
    * Participation in another clinical trial (currently or within the last 30 days)
    * Use of medications that are contraindicated or otherwise interfere with the effects of the study medications (monoamine oxidase inhibitors, antidepressants, sedatives etc.)

    Primary Outcomes
    • Effect of duloxetine on the subjective response to MDMA 24h
    Secondary Outcomes
    • Effect of duloxetine on cardiovascular effects of MDMA 6h
    • Effect of duloxetine on pharmacokinetics of MDMA 6h
    • Effect of MDMA on duloxetine pharmacokinetics 6h
    • Tolerability of MDMA and duloxetine 7 days
    • Effect of duloxetine on neuroendocrine responses to MDMA 6h
    Other Outcomes

    • Effects of genetic polymorphisms on the response to MDMA

    More Details

    NCT Number: NCT00990067
    Other IDs: EKBB 253/09
    Study URL: https://clinicaltrials.gov/study/NCT00990067
    Last updated: Sep 29, 2023