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Pharmacological Interaction Between Clonidine and Methylenedioxymethamphetamine (MDMA)

Primary Purpose

Mood Disorder, Substance-Related Disorders, Amphetamine-Related Disorders

Status
Completed
Phase
Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
3,4-Methylenedioxymethamphetamine
Clonidine
placebo
Sponsored by
University Hospital, Basel, Switzerland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Mood Disorder focused on measuring MDMA, norepinephrine, alpha2 receptor, Ecstasy, stimulant

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

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.)

Sites / Locations

  • Clinical Pharmacology & Toxicology, University Hospital Basel

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

clonidine, MDMA, placebo

Arm Description

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.

Outcomes

Primary Outcome Measures

Effect of clonidine on the subjective response to MDMA

Secondary Outcome Measures

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

Full Information

First Posted
May 31, 2010
Last Updated
January 24, 2013
Sponsor
University Hospital, Basel, Switzerland
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1. Study Identification

Unique Protocol Identification Number
NCT01136278
Brief Title
Pharmacological Interaction Between Clonidine and Methylenedioxymethamphetamine (MDMA)
Official Title
Pharmacological Interaction Between Clonidine and 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
July 2010 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
December 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Basel, Switzerland

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mood Disorder, Substance-Related Disorders, Amphetamine-Related Disorders
Keywords
MDMA, norepinephrine, alpha2 receptor, Ecstasy, stimulant

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
clonidine, MDMA, placebo
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
3,4-Methylenedioxymethamphetamine
Other Intervention Name(s)
MDMA, Ecstasy
Intervention Description
125 mg, single dose
Intervention Type
Drug
Intervention Name(s)
Clonidine
Intervention Description
150 μg per os
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
capsules identical to MDMA or clonidine
Primary Outcome Measure Information:
Title
Effect of clonidine on the subjective response to MDMA
Time Frame
24 h
Secondary Outcome Measure Information:
Title
Effect of clonidine on cardiovascular effects of MDMA
Time Frame
8 h
Title
Effect of clonidine on pharmacokinetics of MDMA
Time Frame
8 h
Title
Effect of MDMA on clonidine pharmacokinetics
Time Frame
8 h
Title
Tolerability of MDMA and clonidine
Time Frame
8 h
Title
Effect of clonidine on neuroendocrine responses to MDMA
Time Frame
8 h
Other Pre-specified Outcome Measures:
Title
Genetic polymorphisms
Description
Effects of genetic polymorphisms on the response to MDMA
Time Frame
assessed after study completion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthias E Liechti, MD
Organizational Affiliation
Department of Internal Medicine, Division of Pharmacology & Toxicology, University Hospital Basel, Switzerland
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinical Pharmacology & Toxicology, University Hospital Basel
City
Basel
ZIP/Postal Code
4053
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
29912955
Citation
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.
Results Reference
derived
PubMed Identifier
22700038
Citation
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.
Results Reference
derived

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Pharmacological Interaction Between Clonidine and Methylenedioxymethamphetamine (MDMA)

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