Influence of Bupropion on the Effects of MDMA

Condition(s) targeted: Healthy; Substance-related Disorders

Intervention: MDMA (Drug); Bupropion (Drug); Placebo (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: University Hospital, Basel, Switzerland

Official(s) and/or principal investigator(s):
Matthias E Liechti, MD, MAS, Principal Investigator, Affiliation: University Hospital, Basel, Switzerland

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.

Official title: Influence of Bupropion on the Effects of MDMA

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

Primary outcome: Positive Mood Effects

Secondary outcome:

Blood pressure(mmHg)during 10 hours

Neuroendocrine plasma levels

Drug plasma levels

Heart rate (bpm)

Body temperature

Effects on social cognition (emotion recognition and empathy)

Influence of genetic cytochrome P450 2D6 polymorphisms on the metabolism of MDMA

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.

Minimum age: 18 Years. Maximum age: 45 Years. Gender(s): Both.

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

University Hospital Basel, Basel, Basel-Stadt 4000, Switzerland

Starting date: January 2013
Last updated: October 21, 2013