Pharmacological Interaction Between Clonidine and Methylenedioxymethamphetamine (MDMA)

Phase 1

Completed

• Conditions: Mood Disorder; Substance-Related Disorders; Amphetamine-Related Disorders
• Interventions: Drug: 3,4-Methylenedioxymethamphetamine; Drug: Clonidine; Drug: placebo

• Registration Number: NCT01136278
• Lead Sponsor: University Hospital, Basel, Switzerland

Brief Summary

The purpose of this study is to determinate the effect of a pre-treatment with centrally acting alpha2-receptor agonist clonidine on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"). The investigators hypothesize that clonidine will attenuate the subjective and cardiovascular response to MDMA.

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. It is unknown which of these monoamines mainly contributes to the subjective and physiological effects of MDMA in humans. Clonidine is a centrally acting alpha2-receptor agonist and sympatholytic which attenuates the release of NE from presynaptic nerve terminals and also lowers NE plasma concentration. To determine the role of NE in the response to MDMA in humans we test the effects of a clonidine pretreatment on the pharmacodynamics and pharmacokinetics of MDMA. We use a randomized double-blind placebo-controlled cross-over design with four experimental sessions. Clonidine (150 μg) or placebo will be administered 1 h before the administration of MDMA (125 mg) or placebo to 16 healthy volunteers. Subjective and cardiovascular responses will be repeatedly assessed throughout the experiments and plasma samples are collected for pharmacokinetics. We hypothesize that clonidine will significantly attenuate predominantly the cardiovascular response to MDMA.

Study Timeline

• Study First Submitted: 2010-05-31
• Study First Submitted QC: 2010-06-02
• Study First Posted: 2010-06-03
• Study Start: 2010-07
• Primary Completion: 2010-12
• Study Completion: 2010-12
• Status Verified: 2013-01
• Last Update Submitted: 2013-01-24
• Last Update Posted: 2013-01-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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

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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.)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
clonidine, MDMA, placebo	Clonidine	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.
clonidine, MDMA, placebo	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.
clonidine, MDMA, placebo	3,4-Methylenedioxymethamphetamine	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.

Primary Outcome Measures

Name	Time	Method
Effect of clonidine on the subjective response to MDMA	24 h

Secondary Outcome Measures

Name	Time	Method
Effect of clonidine on cardiovascular effects of MDMA	8 h
Effect of clonidine on pharmacokinetics of MDMA	8 h
Effect of MDMA on clonidine pharmacokinetics	8 h
Tolerability of MDMA and clonidine	8 h
Effect of clonidine on neuroendocrine responses to MDMA	8 h

Trial Locations

Locations (1)

Clinical Pharmacology & Toxicology, University Hospital Basel; 🇨🇭 Basel, Switzerland