Clinical Trial: Interaction Between Reboxetine and 3,4-Methylenedioxymethamphetamine: Pharmacodynamics (PD) and Pharmacokinetics (PK)

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

Official Title: Pharmacological Interaction Between Reboxetine and 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy): Pharmacological Effects and Pharmacokinetics

Brief Summary: MDMA releases dopamine, serotonin, and norepinephrine in the brain. Serotonin uptake inhibitors have been shown to interact with 3,4-Methylenedioxymethamphetamine (MDMA) and to decrease its psychoactive and cardiovascular stimulant effects. This finding indicates that MDMA acts in part by releasing serotonin through the serotonin uptake site. However, in vitro studies show that MDMA binds more potently to the norepinephrine uptake site that to the the serotonin or dopamine uptake transporter. In addition, norepinephrine uptake site blockers such antidepressant drugs attenuate some of the behavioral effects of MDMA in animals. These preclinical data indicate that norepinephrine may also contribute to the response to MDMA in humans. To test this hypothesis this study evaluates the interacting effects of the selective norepinephrine transporter inhibitor reboxetine on the subjective and cardiovascular stimulant effects of MDMA in healthy volunteers.

Detailed Summary:

The study will use a randomized double-blind cross-over design with four experimental sessions. Reboxetine (8 mg) or placebo will be administered the night before the experimental session and 1 h before the administration of MDMA (125 mg) or placebo to 16 healthy volunteers. Subjective and cardiovascular responses and plasma samples for pharmacokinetics will be repeatedly assessed throughout the experiments.

We hypothesize that the highly selective norepinephrine uptake inhibitor reboxetine will attenuate subjective and especially heart rate and blood pressure responses to MDMA. Such a result would indicate that norepinephrine is critically involved in the pharmacology of MDMA and may provide helpful in the use and development of treatments for Ecstasy intoxications.


Sponsor: University Hospital, Basel, Switzerland

Current Primary Outcome: Effect of reboxetine on subjective responses to MDMA [ Time Frame: 24h ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Effect of reboxetine on physiological responses to MDMA [ Time Frame: 24h ]
  • Effects of reboxetine on pharmacokinetics of MDMA [ Time Frame: 24h ]
  • Tolerability of MDMA and reboxetine [ Time Frame: 7 days ]
  • Effect of reboxetine on neuroendocrine responses to MDMA [ Time Frame: 24h ]


Original Secondary Outcome: Same as current

Information By: University Hospital, Basel, Switzerland

Dates:
Date Received: April 22, 2009
Date Started: April 2009
Date Completion:
Last Updated: January 24, 2013
Last Verified: January 2013