Mood Disorder, Substance-Related Disorders, Amphetamine-Related Disorders
Conditions
Keywords
MDMA, carvedilol, norepinephrine, alpha - beta receptor, Ecstasy, stimulant
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.
Interventions
125 mg per os, single dose
DRUGcarvedilol
50 mg per os, single dose
DRUGplacebo
capsules identical to MDMA or carvedilol
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Effect of carvedilol on the blood pressure response to MDMA | 24 h |
Secondary
| Measure | 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 | 7 h |
Other
| Measure | Time frame | Description |
|---|---|---|
| Genetic polymorphisms | assessed after study completion | Effects of genetic polymorphisms on the response to MDMA |
Countries
Switzerland
Outcome results
None listed