Influence of Bupropion on the Effects of MDMA

Healthy Clinical Trial

Official title:

Influence of Bupropion on the Effects of MDMA

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01771874
• Other study ID #: EK 190/12
• Status: Completed
• Phase: Phase 1
• First received: October 24, 2012
• Last updated: January 20, 2016
• Start date: January 2013
• Est. completion date: September 2013

Study information

• Verified date: January 2016
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: September 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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

Study Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy
• Substance-related Disorders

Intervention

Drug:
• MDMA
125 mg per os, single dose
• Bupropion
Bupropion will be administered in a dose of 150mg (Wellbutrin XR) once-daily in the morning for three days followed by 300mg (2x150mg) for 4 days before the test day. On the test day, a final dose of 300mg will administered 2 hours before the administration of MDMA 125 mg or placebo.
• Placebo
per os

Locations

Country	Name	City	State
Switzerland	University Hospital Basel	Basel	Basel-Stadt

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Positive Mood Effects	A significant reduction of the (100-mm Visual Analog Scale) positive mood response to MDMA by bupropion.	24 hours	No
Secondary	Blood pressure(mmHg)during 10 hours		10 hours	No
Secondary	Neuroendocrine plasma levels	assessed: prolactin, cortisol, epinephrine, norepinephrine, oxytocin, pro-vasopressin, vasopressin, estrogen,and progesterone	10 hours	No
Secondary	Drug plasma levels	The plasma concentration of MDMA and bupropion is repetitively assessed	24 hours	No
Secondary	Heart rate (bpm)		10 hours	No
Secondary	Body temperature		10 hours	No
Secondary	Effects on social cognition (emotion recognition and empathy)		10 hours	No
Secondary	Influence of genetic cytochrome P450 2D6 polymorphisms on the metabolism of MDMA	We will assess the effects of the subjects' genotype and phenotype on MDMA and its metabolites plasma concentrations.	24hours	No