Pharmacological Interaction Between Doxazosin and Methylenedioxymethamphetamine (MDMA)
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.
|Study Design:||Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
|Official Title:||Interactive Effects of Doxazosin and 3,4-Methylenedioxymethamphetamine (MDMA) in Healthy Subjects|
- Systolic and diastolic blood pressure (mmHg) during 6 hours [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
- Subjective effects during 6 hours [ Time Frame: 6 hours ] [ Designated as safety issue: No ]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 [ Time Frame: 6 hours ] [ Designated as safety issue: No ]neuroendocrine parameters assessed: prolactin, cortisol, epinephrine, norepinephrine, oxytocin, pro-vasopressin, vasopressin, estrogen,and progesterone
- MDMA plasma levels during 6 hours [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
- Genetic polymorphisms [ Time Frame: assessed after study completion ] [ Designated as safety issue: No ]Effects of MDMA on genetic polymorphisms
- Genetic polymorphisms [ Time Frame: assessed after study completion ] [ Designated as safety issue: No ]Effects of genetic polymorphisms on the response to MDMA
- Prosocial behavior [ Time Frame: 5 hours ] [ Designated as safety issue: No ]Effects on prosociality will be assessed by the Social Value Orientation slide-measurement test.
- Empathy [ Time Frame: 5 hours ] [ Designated as safety issue: No ]Emotional empathy will be assessed by the Multifaceted Empathy Test (MET). Cognitive empathy will be assessed by Facial Emotion Recognition Tests and the MET.
|Study Start Date:||July 2011|
|Study Completion Date:||January 2012|
|Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
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.
125 mg per os, single dose
Other Names: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 Name: CarduraDrug: placebo
capsules identical to MDMA or doxazosin
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01386177
|University Hospital Basel|
|Basel, Switzerland, 4031|
|Principal Investigator:||Matthias E Liechti, MD||University Hospital, Basel, Switzerland|