Pharmacological Interaction Between Clonidine and Methylenedioxymethamphetamine (MDMA)

Condition(s) targeted: Mood Disorder; Substance-Related Disorders; Amphetamine-Related Disorders

Intervention: 3,4-Methylenedioxymethamphetamine (Drug); Clonidine (Drug); placebo (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: University Hospital, Basel, Switzerland

Official(s) and/or principal investigator(s):
Matthias E Liechti, MD, Principal Investigator, Affiliation: Department of Internal Medicine, Division of Pharmacology & Toxicology, University Hospital Basel, Switzerland

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.

Official title: Pharmacological Interaction Between Clonidine and 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy)

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

Primary outcome: Effect of clonidine on the subjective response to MDMA

Secondary outcome:

Effect of clonidine on cardiovascular effects of MDMA

Effect of clonidine on pharmacokinetics of MDMA

Effect of MDMA on clonidine pharmacokinetics

Tolerability of MDMA and clonidine

Effect of clonidine on neuroendocrine responses 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.

Minimum age: 18 Years. Maximum age: 45 Years. Gender(s): Both.

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.)

Clinical Pharmacology & Toxicology, University Hospital Basel, Basel 4053, Switzerland

Starting date: July 2010
Last updated: January 24, 2013