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

Sponsor
University Hospital, Basel, Switzerland (Other)
Overall Status
Completed
CT.gov ID
NCT00990067
Collaborator
(none)
16
Enrollment
1
Location
1
Arm
5.9
Duration (Months)
2.7
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
16 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Basic Science
Official Title:
Pharmacological Interaction Between Duloxetine and 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy): Pharmacodynamics (PD) and Pharmacokinetics (PK)
Study Start Date :
Nov 1, 2009
Actual Primary Completion Date :
May 1, 2010
Actual Study Completion Date :
May 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Other: duloxetine, MDMA, placebo

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.

Drug: 3,4-Methylenedioxymethamphetamine
125 mg, single dose
Other Names:
  • MDMA
  • Ecstasy

    • Drug: Duloxetine
    120 mg two doses 12h and 2h before MDMA
    Other Names:
  • Cymbalta (r)

    • Drug: Placebo
    capsules identical to MDMA or duloxetine

    Outcome Measures

    Primary Outcome Measures

    1. Effect of duloxetine on the subjective response to MDMA [24h]

    Secondary Outcome Measures

    1. Effect of duloxetine on cardiovascular effects of MDMA [6h]

    2. Effect of duloxetine on pharmacokinetics of MDMA [6h]

    3. Effect of MDMA on duloxetine pharmacokinetics [6h]

    4. Tolerability of MDMA and duloxetine [7 days]

    5. Effect of duloxetine on neuroendocrine responses to MDMA [6h]

    Other Outcome Measures

    1. Genetic polymorphisms [assessed after study completion]

      Effects of genetic polymorphisms on the response to MDMA

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    All
    Accepts 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.)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Clinical Pharmacology & Toxicology, University Hospital Basel Basel Switzerland 4031

    Sponsors and Collaborators

    • University Hospital, Basel, Switzerland

    Investigators

    • Principal Investigator: Matthias E Liechti, MD, Department of Internal Medicine, Division of Pharmacology & Toxicology, University Hospital Basel, Switzerland

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University Hospital, Basel, Switzerland
    ClinicalTrials.gov Identifier:
    NCT00990067
    Other Study ID Numbers:
    • EKBB 253/09
    First Posted:
    Oct 6, 2009
    Last Update Posted:
    Jan 25, 2013
    Last Verified:
    Jan 1, 2013
    Keywords provided by University Hospital, Basel, Switzerland
    MDMA
    serotonin
    norepinephrine
    Ecstasy
    stimulant
    Additional relevant MeSH terms:
    Disease
    Substance-Related Disorders
    Amphetamine-Related Disorders
    Mood Disorders
    Duloxetine Hydrochloride
    N-Methyl-3,4-methylenedioxyamphetamine

    Study Results

    No Results Posted as of Jan 25, 2013