Pharmacological Interaction Between Clonidine and Methylenedioxymethamphetamine (MDMA)

NCT ID: NCT01136278

Last Updated: 2013-01-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2010-12-31

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.

Conditions

Mood Disorder; Substance-Related Disorders; Amphetamine-Related Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

3,4-Methylenedioxymethamphetamine

Intervention Type: DRUG

125 mg, single dose

Clonidine

Intervention Type: DRUG

150 μg per os

placebo

Intervention Type: DRUG

capsules identical to MDMA or clonidine

Interventions

3,4-Methylenedioxymethamphetamine

125 mg, single dose

Intervention Type: DRUG

Clonidine

150 μg per os

Intervention Type: DRUG

placebo

capsules identical to MDMA or clonidine

Intervention Type: DRUG

Other Intervention Names

MDMA; Ecstasy

Eligibility 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.)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthias E Liechti, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Internal Medicine, Division of Pharmacology & Toxicology, University Hospital Basel, Switzerland

Locations

Clinical Pharmacology & Toxicology, University Hospital Basel

Basel, Basel, Switzerland

Countries

Switzerland

References

Vizeli P, Liechti ME. Oxytocin receptor gene variations and socio-emotional effects of MDMA: A pooled analysis of controlled studies in healthy subjects. PLoS One. 2018 Jun 18;13(6):e0199384. doi: 10.1371/journal.pone.0199384. eCollection 2018.

Reference Type: DERIVED

PMID: 29912955 (View on PubMed)

Hysek CM, Liechti ME. Effects of MDMA alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin on pupillary light reflex. Psychopharmacology (Berl). 2012 Dec;224(3):363-76. doi: 10.1007/s00213-012-2761-6. Epub 2012 Jun 15.

Reference Type: DERIVED

PMID: 22700038 (View on PubMed)

Other Identifiers

EK 353/09

Identifier Type: -

Identifier Source: org_study_id