Pharmacological Interaction Between Doxazosin and Methylenedioxymethamphetamine (MDMA)

Phase 1

Completed

• Conditions: Substance-Related Disorders; Mood Disorder; Amphetamine-Related Disorders
• Interventions: Drug: 3,4-Methylenedioxymethamphetamine; Drug: Doxazosin; Drug: placebo

• Registration Number: NCT01386177
• Lead Sponsor: University Hospital, Basel, Switzerland

Brief Summary

The purpose of this study is to determinate the effect of a pre-treatment with doxazosin, a alpha1-adrenergic receptor blocker, on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). The investigators hypothesize that doxazosin 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-adrenergic receptors in the response to MDMA in humans the investigators test the effects of the alpha1-receptor blocker doxazosin on the physiological and subjective effects of MDMA. The investigators use a randomized double-blind placebo-controlled cross-over design with four experimental sessions. doxazosin 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 doxazosin will significantly reduce the blood pressure response to MDMA.

Study Timeline

• Study First Submitted: 2011-06-03
• Study First Submitted QC: 2011-06-29
• Study First Posted: 2011-06-30
• Study Start: 2011-07
• Primary Completion: 2012-01
• Study Completion: 2012-01
• Status Verified: 2018-12
• Last Update Submitted: 2018-12-10
• Last Update Posted: 2018-12-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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.)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
doxazosin, MDMA, placebo	placebo	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.
doxazosin, MDMA, placebo	3,4-Methylenedioxymethamphetamine	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.
doxazosin, MDMA, placebo	Doxazosin	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.

Primary Outcome Measures

Name	Time	Method
Systolic and diastolic blood pressure (mmHg) during 6 hours	6 hours

Secondary Outcome Measures

Name	Time	Method
MDMA plasma levels during 6 hours	6 hours
Genetic polymorphisms	assessed after study completion	Effects of genetic polymorphisms on the response to MDMA
Subjective effects during 6 hours	6 hours	subjective effects are going to be assessed by various standardized questionnaires (e.g. visual analogue scales (VAS), the 5 dimension Altered State of consciousness questionnaire, or the adjective mood rating scale (AMRS).)
Neuroendocrine plasma levels during 6 hours	6 hours	neuroendocrine parameters assessed: prolactin, cortisol, epinephrine, norepinephrine, oxytocin, pro-vasopressin, vasopressin, estrogen,and progesterone

Trial Locations

Locations (1)

University Hospital Basel; 🇨🇭 Basel, Switzerland