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Interaction Between Duloxetine and 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy)

Primary Purpose

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

Status

Completed

Phase

Phase 1

Locations

Switzerland

Study Type

Interventional

Intervention

3,4-Methylenedioxymethamphetamine

Duloxetine

Placebo

About this trial

This is an interventional basic science trial for Mood Disorder focused on measuring MDMA, serotonin, norepinephrine, 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

Other

Arm Label

duloxetine, 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 duloxetine on the subjective response to MDMA

Secondary Outcome Measures

Effect of duloxetine on cardiovascular effects of MDMA

Effect of duloxetine on pharmacokinetics of MDMA

Effect of MDMA on duloxetine pharmacokinetics

Tolerability of MDMA and duloxetine

Effect of duloxetine on neuroendocrine responses to MDMA

Full Information

NCT ID

NCT00990067

First Posted

October 5, 2009

Last Updated

January 24, 2013

Sponsor

University Hospital, Basel, Switzerland

1. Study Identification

Unique Protocol Identification Number

NCT00990067

Brief Title

Interaction Between Duloxetine and 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy)

Official Title

Pharmacological Interaction Between Duloxetine and 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy): Pharmacodynamics (PD) and Pharmacokinetics (PK)

Study Type

Interventional

2. Study Status

Record Verification Date

January 2013

Overall Recruitment Status

Completed

Study Start Date

November 2009 (undefined)

Primary Completion Date

May 2010 (Actual)

Study Completion Date

May 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 the combined serotonin (5-HT) and norepinephrine (NE) transport blocker duloxetine on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"). The investigators hypothesize that duloxetine 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 through an interaction with the corresponding presynaptic monoamine uptake transporter. 5-HT transport inhibitors block MDMA-induced 5-HT release in vitro or in animals and also attenuate the subjective and cardiovascular response to MDMA in humans. NE transport inhibitors similarly prevent the MDMA-induced release of NE in cell assays and attenuate behavioral effects of MDMA in animals. Effects of the NE transporter inhibitor reboxetine on the response to MDMA in humans are currently investigated. Here we suggest evaluating effects of pretreatment with the combined 5-HT and NE transport blocker duloxetine on the pharmacodynamics and pharmacokinetics of MDMA. The study will use a randomized double-blind cross-over design with four experimental sessions. Duloxetine (120 mg) or placebo will be administered 16 h and 4 h before the administration of MDMA (125 mg) or placebo to 16 healthy volunteers. Subjective and cardiovascular responses and plasma samples for pharmacokinetics will be repeatedly assessed throughout the experiments.

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, serotonin, norepinephrine, 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

duloxetine, MDMA, placebo

Arm Type

Other

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)

Duloxetine

Other Intervention Name(s)

Cymbalta (r)

Intervention Description

120 mg two doses 12h and 2h before MDMA

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

capsules identical to MDMA or duloxetine

Primary Outcome Measure Information:

Title

Effect of duloxetine on the subjective response to MDMA

Time Frame

24h

Secondary Outcome Measure Information:

Title

Effect of duloxetine on cardiovascular effects of MDMA

Time Frame

Title

Effect of duloxetine on pharmacokinetics of MDMA

Time Frame

Title

Effect of MDMA on duloxetine pharmacokinetics

Time Frame

Title

Tolerability of MDMA and duloxetine

Time Frame

7 days

Title

Effect of duloxetine on neuroendocrine responses to MDMA

Time Frame

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 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

4031

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

PubMed Identifier

22574166

Citation

Hysek CM, Simmler LD, Nicola VG, Vischer N, Donzelli M, Krahenbuhl S, Grouzmann E, Huwyler J, Hoener MC, Liechti ME. Duloxetine inhibits effects of MDMA ("ecstasy") in vitro and in humans in a randomized placebo-controlled laboratory study. PLoS One. 2012;7(5):e36476. doi: 10.1371/journal.pone.0036476. Epub 2012 May 4.

Results Reference

derived

PubMed Identifier

21715530

Citation

Simmler LD, Hysek CM, Liechti ME. Sex differences in the effects of MDMA (ecstasy) on plasma copeptin in healthy subjects. J Clin Endocrinol Metab. 2011 Sep;96(9):2844-50. doi: 10.1210/jc.2011-1143. Epub 2011 Jun 29.

Results Reference

derived

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Interaction Between Duloxetine and 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy)

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