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

Substance-Related Disorders Clinical Trial

Official title:

Pharmacological Interaction Between Duloxetine and 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy): Pharmacodynamics (PD) and Pharmacokinetics (PK)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00990067
• Other study ID #: EKBB 253/09
• Status: Completed
• Phase: Phase 1
• First received: October 5, 2009
• Last updated: January 24, 2013
• Start date: November 2009
• Est. completion date: May 2010

Study information

• Verified date: January 2013
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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.)

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

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

Intervention

Drug:
• 3,4-Methylenedioxymethamphetamine
125 mg, single dose
• Duloxetine
120 mg two doses 12h and 2h before MDMA
• Placebo
capsules identical to MDMA or duloxetine

Locations

Country	Name	City	State
Switzerland	Clinical Pharmacology & Toxicology, University Hospital Basel	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Genetic polymorphisms	Effects of genetic polymorphisms on the response to MDMA	assessed after study completion	No
Primary	Effect of duloxetine on the subjective response to MDMA		24h	No
Secondary	Effect of duloxetine on cardiovascular effects of MDMA		6h	No
Secondary	Effect of duloxetine on pharmacokinetics of MDMA		6h	No
Secondary	Effect of MDMA on duloxetine pharmacokinetics		6h	No
Secondary	Tolerability of MDMA and duloxetine		7 days	No
Secondary	Effect of duloxetine on neuroendocrine responses to MDMA		6h	No