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.
Topic Healthy Subjects
Country Switzerland
Visit trial
Status
Completed
Results Published
Start date
07 January 2011
End date
01 January 2012
Chance of happening
100%
Phase
Phase I
Design
Blinded
Type
Interventional
Generation
First
Participants
16
Sex
All
Age
18- 45
Therapy
No
Trial Details
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.NCT Number NCT01386177
Sponsors & Collaborators
University of BaselThe University of Basel Department of Biomedicine hosts the Liechti Lab research group, headed by Matthias Liechti.
Papers
Effects of MDMA alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin on pupillary light reflexThis study analysed data from five separate clinical trials (n=80) that explored the effects of MDMA on pupillary light reflex and the effects following pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin, respectively. MDMA produced mydriasis, prolonged the latency, reduced the response to light and shortened the recovery time and this impairment returned to normal 6 hours post-treatment. Only reboxetine and duloxetine interacted with the effects of MDMA on pupillary function.
α₁-Adrenergic receptors contribute to the acute effects of 3,4-methylenedioxymethamphetamine in humans
This study assessed the effects of the α₁-noradrenergic receptor antagonist, doxazosin (8mg/day for 3 days), on the acute response to MDMA (125mg) in healthy subjects (n=16). Doxazosin reduced MDMA-induced elevations in blood pressure, and body temperature, and moderately attenuated positive mood but enhanced tachycardia associated with MDMA.