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The purpose of this study is to determinate the effect of a pre-treatment with carvedilol, a alpha- and beta-adrenergic receptor blocker, on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"). The investigators hypothesize that carvedilol will attenuate the cardiovascular and subjective response to MDMA.
3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is widely used by young people for its euphoric effects. MDMA releases serotonin (5-HT), dopamine, and norepinephrine (NE). NE release is thought to mediate the cardiovascular effects of MDMA and may also contribute to its psychostimulant effects. However, the functional role of adrenergic postsynaptic receptors in the cardiovascular and subjective effects of MDMA in humans is largely unclear. To determine the role of alpha- and beta adrenergic receptors in the response to MDMA in humans the investigators test the effects of the alpha- and beta-receptor blocker carvedilol on the physiological and subjective effects of MDMA. The investigators use a randomized double-blind placebo-controlled cross-over design with four experimental sessions. Carvedilol or placebo will be administered 1 h 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 carvedilol will significantly reduce the blood pressure response to MDMA.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| carvedilol, MDMA, 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 3,4-Methylenedioxymethamphetamine | Drug | 125 mg per os, single dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Effect of carvedilol on the blood pressure response to MDMA | 24 h |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of carvedilol on the subjective response to MDMA | 24 h | |
| Effect of carvedilol on neuroendocrine effects of MDMA | 7 h | |
| Effect of carvedilol on pharmacokinetics of MDMA |
| Measure | Description | Time Frame |
|---|---|---|
| Genetic polymorphisms | Effects of genetic polymorphisms on the response to MDMA | assessed after study completion |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Matthias E Liechti, MD | Department of Internal Medicine, Division of Pharmacology & Toxicology, University Hospital Basel, Switzerland | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Pharmacology & Toxicology, University Hospital Basel | Basel | 4053 | 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. | |
| 22700038 | Derived | Hysek CM, Liechti ME. Effects of MDMA alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin on pupillary light reflex. Psychopharmacology (Berl). 2012 Dec;224(3):363-76. doi: 10.1007/s00213-012-2761-6. Epub 2012 Jun 15. |
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| ID | Term |
|---|---|
| D019964 | Mood Disorders |
| D019966 | Substance-Related Disorders |
| D019969 | Amphetamine-Related Disorders |
| ID | Term |
|---|---|
| D001523 | Mental Disorders |
| D064419 | Chemically-Induced Disorders |
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| ID | Term |
|---|---|
| D018817 | N-Methyl-3,4-methylenedioxyamphetamine |
| D000077261 | Carvedilol |
| ID | Term |
|---|---|
| D000662 | Amphetamines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D000588 | Amines |
| D009930 |
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| carvedilol | Drug | 50 mg per os, single dose |
|
| placebo | Drug | capsules identical to MDMA or carvedilol |
|
| 7 h |
| Organic Chemicals |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D020005 | Propanols |
| D002227 | Carbazoles |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D006575 | Heterocyclic Compounds, 3-Ring |