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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT00990067
First received: October 5, 2009
Last updated: January 24, 2013
Last verified: January 2013
  Purpose

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 Intervention Phase
Mood Disorder
Substance-Related Disorders
Amphetamine-Related Disorders
Drug: 3,4-Methylenedioxymethamphetamine
Drug: Duloxetine
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Pharmacological Interaction Between Duloxetine and 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy): Pharmacodynamics (PD) and Pharmacokinetics (PK)

Resource links provided by NLM:


Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • Effect of duloxetine on the subjective response to MDMA [ Time Frame: 24h ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Effect of duloxetine on cardiovascular effects of MDMA [ Time Frame: 6h ] [ Designated as safety issue: No ]
  • Effect of duloxetine on pharmacokinetics of MDMA [ Time Frame: 6h ] [ Designated as safety issue: No ]
  • Effect of MDMA on duloxetine pharmacokinetics [ Time Frame: 6h ] [ Designated as safety issue: No ]
  • Tolerability of MDMA and duloxetine [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Effect of duloxetine on neuroendocrine responses to MDMA [ Time Frame: 6h ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Genetic polymorphisms [ Time Frame: assessed after study completion ] [ Designated as safety issue: No ]
    Effects of genetic polymorphisms on the response to MDMA


Enrollment: 16
Study Start Date: November 2009
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Cymbalta (r)
Drug: Placebo
capsules identical to MDMA or duloxetine

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00990067

Locations
Switzerland
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
  More Information

No publications provided by University Hospital, Basel, Switzerland

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT00990067     History of Changes
Other Study ID Numbers: EKBB 253/09
Study First Received: October 5, 2009
Last Updated: January 24, 2013
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Basel, Switzerland:
MDMA
serotonin
norepinephrine
Ecstasy
stimulant

Additional relevant MeSH terms:
Amphetamine-Related Disorders
Substance-Related Disorders
Mood Disorders
Chemically-Induced Disorders
Mental Disorders
N-Methyl-3,4-methylenedioxyamphetamine
Duloxetine
Hallucinogens
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Uptake Inhibitors
Adrenergic Agents
Neurotransmitter Uptake Inhibitors
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antidepressive Agents
Serotonin Uptake Inhibitors
Dopamine Uptake Inhibitors
Dopamine Agents

ClinicalTrials.gov processed this record on August 28, 2014