Pharmacological Interaction Between Clonidine and Methylenedioxymethamphetamine (MDMA)

Sponsor

University Hospital, Basel, Switzerland (Other)

Overall Status

Completed

CT.gov ID

NCT01136278

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

3.2

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 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.

Condition or Disease	Intervention/Treatment	Phase
Mood Disorder Substance-Related Disorders Amphetamine-Related Disorders	Drug: 3,4-Methylenedioxymethamphetamine Drug: Clonidine Drug: placebo	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. 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 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 Clonidine and 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy)

Study Start Date :

Jul 1, 2010

Actual Primary Completion Date :

Dec 1, 2010

Actual Study Completion Date :

Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: clonidine, 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: Clonidine 150 μg per os Drug: placebo capsules identical to MDMA or clonidine

Arm

Intervention/Treatment

Experimental: clonidine, 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: Clonidine

150 μg per os

Drug: placebo

capsules identical to MDMA or clonidine

Outcome Measures

Primary Outcome Measures

Effect of clonidine on the subjective response to MDMA [24 h]

Secondary Outcome Measures

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]

Other Outcome Measures

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	4053

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