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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
16
125 mg per os, single dose
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.
per os
University Hospital Basel
Basel, Canton of Basel-City, Switzerland
Positive Mood Effects
A significant reduction of the (100-mm Visual Analog Scale) positive mood response to MDMA by bupropion.
Time frame: 24 hours
Blood pressure(mmHg)during 10 hours
Time frame: 10 hours
Neuroendocrine plasma levels
assessed: prolactin, cortisol, epinephrine, norepinephrine, oxytocin, pro-vasopressin, vasopressin, estrogen,and progesterone
Time frame: 10 hours
Drug plasma levels
The plasma concentration of MDMA and bupropion is repetitively assessed
Time frame: 24 hours
Heart rate (bpm)
Time frame: 10 hours
Body temperature
Time frame: 10 hours
Effects on social cognition (emotion recognition and empathy)
Time frame: 10 hours
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.
Time frame: 24hours
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