Clinical Trial: Pharmacological Interaction Between Doxazosin and Methylenedioxymethamphetamine (MDMA)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 Summary: 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.
Sponsor: University Hospital, Basel, Switzerland

Current Primary Outcome: Systolic and diastolic blood pressure (mmHg) during 6 hours [ Time Frame: 6 hours ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Subjective effects during 6 hours [ Time Frame: 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 [ Time Frame: 6 hours ]
    neuroendocrine parameters assessed: prolactin, cortisol, epinephrine, norepinephrine, oxytocin, pro-vasopressin, vasopressin, estrogen,and progesterone
  • MDMA plasma levels during 6 hours [ Time Frame: 6 hours ]
  • Genetic polymorphisms [ Time Frame: assessed after study completion ]
    Effects of MDMA on genetic polymorphisms
  • Genetic polymorphisms [ Time Frame: assessed after study completion ]
    Effects of genetic polymorphisms on the response to MDMA


Original Secondary Outcome:

  • Subjective effects during 6 hours [ Time Frame: 6 hours ]
    subjective effects are going to be assessed by various standardized questionnaires (e.g. visual analogue scales (VAS), the 5 dimenstion Altered State of Conciousness quiestionnaire, or the adjective mood ratinge scale (AMRS).)
  • Neuroendocrine plasma levels during 6 hours [ Time Frame: 6 hours ]
    neuroendocrine parameters assessed: prolactin, cortisol, epinephrine, norepinephrine, oxytocin, pro-vasopressin, vasopressin, estrogene,and progesterone
  • MDMA plasma levels during 6 hours [ Time Frame: 6 hours ]


Information By: University Hospital, Basel, Switzerland

Dates:
Date Received: June 3, 2011
Date Started: July 2011
Date Completion:
Last Updated: January 20, 2016
Last Verified: January 2016