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Pharmacological Interaction Between Carvedilol and Methylenedioxymethamphetamine (MDMA)

Primary Purpose

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

Status

Completed

Phase

Not Applicable

Locations

Switzerland

Study Type

Interventional

Intervention

3,4-Methylenedioxymethamphetamine

carvedilol

placebo

About this trial

This is an interventional basic science trial for Mood Disorder focused on measuring MDMA, carvedilol, norepinephrine, alpha - beta 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 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

carvedilol, 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 carvedilol on the blood pressure response to MDMA

Secondary Outcome Measures

Effect of carvedilol on the subjective response to MDMA

Effect of carvedilol on neuroendocrine effects of MDMA

Effect of carvedilol on pharmacokinetics of MDMA

Full Information

NCT ID

NCT01270672

First Posted

January 4, 2011

Last Updated

December 10, 2018

Sponsor

University Hospital, Basel, Switzerland

1. Study Identification

Unique Protocol Identification Number

NCT01270672

Brief Title

Pharmacological Interaction Between Carvedilol and Methylenedioxymethamphetamine (MDMA)

Official Title

Effects of Carvedilol on the Cardiovascular and Subjective Response to MDMA (3,4-Methylenedioxymethamphetamine, "Ecstasy")

Study Type

Interventional

2. Study Status

Record Verification Date

December 2018

Overall Recruitment Status

Completed

Study Start Date

January 2011 (undefined)

Primary Completion Date

May 2011 (Actual)

Study Completion Date

May 2011 (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 carvedilol, a alpha- and beta-adrenergic receptor blocker, on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"). The investigators hypothesize that carvedilol will attenuate the cardiovascular and subjective 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), dopamine, and norepinephrine (NE). NE release is thought to mediate the cardiovascular effects of MDMA and may also contribute to its psychostimulant effects. However, the functional role of adrenergic postsynaptic receptors in the cardiovascular and subjective effects of MDMA in humans is largely unclear. To determine the role of alpha- and beta adrenergic receptors in the response to MDMA in humans the investigators test the effects of the alpha- and beta-receptor blocker carvedilol on the physiological and subjective effects of MDMA. The investigators use a randomized double-blind placebo-controlled cross-over design with four experimental sessions. Carvedilol or placebo will be administered 1 h before MDMA or placebo to 16 healthy volunteers. Subjective and cardiovascular responses will be repeatedly assessed throughout the experiments and plasma samples are collected for pharmacokinetics. The primary hypothesis is that carvedilol will significantly reduce the blood pressure 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, carvedilol, norepinephrine, alpha - beta receptor, Ecstasy, stimulant

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

carvedilol, 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, Adam

Intervention Description

125 mg per os, single dose

Intervention Type

Drug

Intervention Name(s)

carvedilol

Intervention Description

50 mg per os, single dose

Intervention Type

Drug

Intervention Name(s)

placebo

Intervention Description

capsules identical to MDMA or carvedilol

Primary Outcome Measure Information:

Title

Effect of carvedilol on the blood pressure response to MDMA

Time Frame

24 h

Secondary Outcome Measure Information:

Title

Effect of carvedilol on the subjective response to MDMA

Time Frame

24 h

Title

Effect of carvedilol on neuroendocrine effects of MDMA

Time Frame

7 h

Title

Effect of carvedilol on pharmacokinetics of MDMA

Time Frame

7 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

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 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 Carvedilol and Methylenedioxymethamphetamine (MDMA)

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