Pharmacological Interaction Between Doxazosin and Methylenedioxymethamphetamine (MDMA)

Sponsor

University Hospital, Basel, Switzerland (Other)

Overall Status

Completed

CT.gov ID

NCT01386177

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Mood Disorder Substance-Related Disorders Amphetamine-Related Disorders	Drug: 3,4-Methylenedioxymethamphetamine Drug: Doxazosin Drug: placebo	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Interactive Effects of Doxazosin and 3,4-Methylenedioxymethamphetamine (MDMA) in Healthy Subjects

Study Start Date :

Jul 1, 2011

Actual Primary Completion Date :

Jan 1, 2012

Actual Study Completion Date :

Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: doxazosin, MDMA, 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.	Drug: 3,4-Methylenedioxymethamphetamine 125 mg per os, single dose Other Names: MDMA ecstasy Drug: Doxazosin 3 days (-64h) before MDMA: 4 mg doxazosin per os. 2 days (-40h) before MDMA: 8 mg doxazosin per os. 1 day (-16h) before MDMA: 8 mg doxazosin per os. Other Names: Cardura Drug: placebo capsules identical to MDMA or doxazosin

Arm

Intervention/Treatment

Experimental: doxazosin, MDMA, 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.

Drug: 3,4-Methylenedioxymethamphetamine

125 mg per os, single dose

Other Names:

MDMA

ecstasy

Drug: Doxazosin

3 days (-64h) before MDMA: 4 mg doxazosin per os. 2 days (-40h) before MDMA: 8 mg doxazosin per os. 1 day (-16h) before MDMA: 8 mg doxazosin per os.

Other Names:

Cardura

Drug: placebo

capsules identical to MDMA or doxazosin

Outcome Measures

Primary Outcome Measures

Systolic and diastolic blood pressure (mmHg) during 6 hours [6 hours]

Secondary Outcome Measures

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
MDMA plasma levels during 6 hours [6 hours]
Genetic polymorphisms [assessed after study completion]
Effects of MDMA on genetic polymorphisms
Genetic polymorphisms [assessed after study completion]
Effects of genetic polymorphisms on the response to MDMA

Other Outcome Measures

Prosocial behavior [5 hours]
Effects on prosociality will be assessed by the Social Value Orientation slide-measurement test.
Empathy [5 hours]
Emotional empathy will be assessed by the Multifaceted Empathy Test (MET). Cognitive empathy will be assessed by Facial Emotion Recognition Tests and the MET.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts 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.)