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

NCT00990067 | Completed Phase 1 DMC

• 1 other identifier: EKBB 253/09
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

MDMA; serotonin; norepinephrine; Ecstasy; stimulant

Outcome Measures

Primary Outcomes (1)

• Effect of duloxetine on the subjective response to MDMA

  24h

Secondary Outcomes (5)

• Effect of duloxetine on cardiovascular effects of MDMA

  6h

• Effect of duloxetine on pharmacokinetics of MDMA

  6h

• Effect of MDMA on duloxetine pharmacokinetics

  6h

• Tolerability of MDMA and duloxetine

  7 days

• Effect of duloxetine on neuroendocrine responses to MDMA

  6h

Other Outcomes (1)

• Genetic polymorphisms

  assessed after study completion

Study Arms (1)

duloxetine, MDMA, placebo

OTHER

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.

Drug: 3,4-Methylenedioxymethamphetamine; Drug: Duloxetine; Drug: Placebo

Interventions

3,4-Methylenedioxymethamphetamine DRUG

125 mg, single dose

Also known as: MDMA, Ecstasy

duloxetine, MDMA, placebo

Duloxetine DRUG

120 mg two doses 12h and 2h before MDMA

Also known as: Cymbalta (r)

duloxetine, MDMA, placebo

Placebo DRUG

capsules identical to MDMA or duloxetine

duloxetine, MDMA, placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.)

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

Clinical Pharmacology & Toxicology, University Hospital Basel

Basel, Basel, 4031, Switzerland

Location

Related Publications (4)

• 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.

  PMID: 29912955 DERIVED

• 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.

  PMID: 22700038 DERIVED

• 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.

  PMID: 22574166 DERIVED

• 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.

  PMID: 21715530 DERIVED

MeSH Terms

Conditions

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

Interventions

N-Methyl-3,4-methylenedioxyamphetamine; Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

Mental Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals; Thiophenes; Sulfur Compounds; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Matthias E Liechti, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2009
• First Posted: October 6, 2009
• Study Start: November 1, 2009
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: January 25, 2013

Record last verified: 2013-01

Locations

CH (1)