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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MDMA, bupropion, placebo | Experimental | 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. The four treatment conditions are placebo-placebo, bupropion-placebo, placebo-MDMA, and bupropion-MDMA. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MDMA | Drug | 125 mg per os, single dose |
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| Measure | Description | Time Frame |
|---|---|---|
| Positive Mood Effects | A significant reduction of the (100-mm Visual Analog Scale) positive mood response to MDMA by bupropion. | 24 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Blood pressure(mmHg)during 10 hours | 10 hours | |
| Neuroendocrine plasma levels | assessed: prolactin, cortisol, epinephrine, norepinephrine, oxytocin, pro-vasopressin, vasopressin, estrogen,and progesterone |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Matthias E Liechti, MD, MAS | University Hospital, Basel, Switzerland | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Basel | Basel | Canton of Basel-City | 4000 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29912955 | Derived | 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. | |
| 28722422 | Derived | 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. |
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| ID | Term |
|---|---|
| D019966 | Substance-Related Disorders |
| ID | Term |
|---|---|
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D018817 | N-Methyl-3,4-methylenedioxyamphetamine |
| D016642 | Bupropion |
| ID | Term |
|---|---|
| D000662 | Amphetamines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D000588 | Amines |
| D009930 |
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| Bupropion | Drug | 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 | Drug | per os |
|
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| 10 hours |
| Drug plasma levels | The plasma concentration of MDMA and bupropion is repetitively assessed | 24 hours |
| Heart rate (bpm) | 10 hours |
| Body temperature | 10 hours |
| Effects on social cognition (emotion recognition and empathy) | 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. | 24hours |
| Organic Chemicals |
| D011427 | Propiophenones |
| D007659 | Ketones |