Clinical trial NCT01771874: Influence of Bupropion on the Effects of MDMA
Official title: Influence of Bupropion on the Effects of MDMA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Substance-related Disorders
Keywords: MDMA
pharmacokinetics
pharmacodynamics
emotions
Mechanism of action of MDMA
Interaction study
Effect of MDMA and bupropion on emotions
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2013-01-18
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to determinate the effect of a pre-treatment with bupropion, a dopamine and norepinephrine transporter inhibitor, on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"). The study will provide further understanding of the dopaminergic regulation of mood.

Detailed description: 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is widely used by young people for its euphoric effects. MDMA releases serotonin (5-HT), dopamine (DA), and norepinephrine (NE). 5-HT release mainly contributes to the subjective effects of MDMA whereas NE release is involved in the cardiovascular and psychostimulant effects of MDMA. DA mediates the reinforcing addiction-related effects of drugs of abuse but it is unclear whether DA contributes to the acute effects of MDMA in humans. To determine the role of DA transporter-mediated DA release in the acute response to MDMA in humans the investigators test the effects of the DA transporter inhibitor bupropion on the physiological and subjective effects of MDMA. The investigators use a randomized double-blind placebo-controlled cross-over design with four experimental sessions. Bupropion or placebo will be administered 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 bupropion reduces the MDMA-induced increase in positive mood.

Eligibility criteria: Inclusion Criteria:

* Age between 18 and 45
* 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 adhere to the protocol and sign the consent form
* Participants must be willing to drink only alcohol-free liquids and no xanthine-containing products(such as coffee, black or green tea, red bull, chocolate) after midnight of the evening before the study session, as well as during the study day
* Participants must be willing not to drive a traffic vehicle within 48 h following MDMA administration
* 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: 18-27 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) or Hypotension (SBP\<85 mmHg). Personal or first-grade history of seizures. Cardiac or neurological disorder
* Current or previous psychotic or major affective disorder
* Psychotic or major affective disorder in first-degree relatives
* Prior illicit drug use (except tetrahydrocannabinol (THC)-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.)
* Tobacco smoking

Primary outcomes:
measure: Positive Mood Effects
timeFrame: 24 hours
Secondary outcomes:
measure: Blood pressure(mmHg)during 10 hours
timeFrame: 10 hours
measure: Neuroendocrine plasma levels
timeFrame: 10 hours
measure: Drug plasma levels
timeFrame: 24 hours
measure: Heart rate (bpm)
timeFrame: 10 hours
measure: Body temperature
timeFrame: 10 hours
measure: Effects on social cognition (emotion recognition and empathy)
timeFrame: 10 hours
measure: Influence of genetic cytochrome P450 2D6 polymorphisms on the metabolism of MDMA
timeFrame: 24hours
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
state: Basel-Stadt
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Matthias E Liechti, MD, MAS
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: Boxler MI, Liechti ME, Schmid Y, Kraemer T, Steuer AE. First Time View on Human Metabolome Changes after a Single Intake of 3,4-Methylenedioxymethamphetamine in Healthy Placebo-Controlled Subjects. J Proteome Res. 2017 Sep 1;16(9):3310-3320. doi: 10.1021/acs.jproteome.7b00294. Epub 2017 Aug 9.