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

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.

Topic Healthy Subjects
Compound MDMA Placebo
Country Switzerland
Visit trial
Status Completed
Results Published
Start date 04 January 2009
End date 03 January 2010
Chance of happening 100%
Phase Phase I
Design Blinded
Type Interventional
Generation First
Participants 16
Sex All
Age 18- 45
Therapy No

Trial Details

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.

NCT Number NCT00886886

Sponsors & Collaborators

University of Basel
The 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 reflex
This 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.

Data attribution

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