Clinical trial NCT01270672: Pharmacological Interaction Between Carvedilol and Methylenedioxymethamphetamine (MDMA)
Official title: Effects of Carvedilol on the Cardiovascular and Subjective Response to MDMA (3,4-Methylenedioxymethamphetamine, "Ecstasy")
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mood Disorder
Substance-Related Disorders
Amphetamine-Related Disorders
Keywords: MDMA
carvedilol
norepinephrine
alpha - beta receptor
Ecstasy
stimulant
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2011-01-05
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Sufficient 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 refrain from taking illicit psychoactive substances during the study.
* Participants must be willing to drink only alcohol-free liquids and no xanthine-containing liquids (such as coffee, black or green tea, red bull, chocolate) after midnight of the evening before the study session. Subjects must agree not to smoke tobacco for 1 h before and 4 hours after MDMA administration.
* Participants must be willing not to drive a traffic vehicle in the evening of the study day.
* 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: 18-25 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). Personal or first-grade history of seizures. Cardiac or neurological disorder.
* Current or previous psychotic or affective disorder
* Psychotic or affective disorder in first-degree relatives
* Prior illicit drug use (except Tetrahydrocannabinol-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.)

Primary outcomes:
measure: Effect of carvedilol on the blood pressure response to MDMA
timeFrame: 24 h
Secondary outcomes:
measure: Effect of carvedilol on the subjective response to MDMA
timeFrame: 24 h
measure: Effect of carvedilol on neuroendocrine effects of MDMA
timeFrame: 7 h
measure: Effect of carvedilol on pharmacokinetics of MDMA
timeFrame: 7 h
Other outcomes:
measure: Genetic polymorphisms
timeFrame: assessed after study completion
Locations:
city: Basel
country: Switzerland
facility: Clinical Pharmacology & Toxicology, University Hospital Basel
Study officials:
affiliation: Department of Internal Medicine, Division of Pharmacology & Toxicology, University Hospital Basel, Switzerland
name: Matthias E Liechti, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.