Effects of the α₂-adrenergic agonist clonidine on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine in healthy volunteers.
Cédric M. Hysek, Robin Brugger, Linda D. Simmler, Marcel Bruggisser, Massimiliano Donzelli, Eric Grouzmann, Marius C. Hoener, Matthias E. Liechti
Journal of Pharmacology and Experimental Therapeutics February 2012 DOI: 10.1124/jpet.111.188425 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, placebo-controlled crossover trial Peer reviewed |
|---|---|
| Sample size | 16 |
| Population | Healthy subjects |
| Interventions | MDMA Clonidine |
| Dose | MDMA 125 mg p.o.; clonidine 150 μg p.o. |
| Duration | Four experimental sessions; clonidine administered 1 h before MDMA |
| Topics | MDMA |
| Key findings | Clonidine given before MDMA reduced MDMA-induced increases in plasma norepinephrine and blood pressure only to the extent that clonidine lowered these measures versus placebo, so no drug interaction was found. Clonidine did not affect MDMA's psychotropic effects or pharmacokinetics. The authors conclude that vesicular norepinephrine release does not critically contribute to MDMA's effects in humans and that the findings do not support α₂-adrenergic agonists for preventing psychostimulant dependence. |
Abstract
The mechanism of action of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) involves the carrier-mediated and potentially vesicular release of monoamines. We assessed the effects of the sympatholytic α₂-adrenergic receptor agonist clonidine (150 μg p.o.), which inhibits the neuronal vesicular release of norepinephrine, on the cardiovascular and psychotropic response to MDMA (125 mg p.o.) in 16 healthy subjects. The study used a randomized, double-blind, placebo-controlled crossover design with four experimental sessions. The administration of clonidine 1 h before MDMA reduced the MDMA-induced increases in plasma norepinephrine concentrations and blood pressure but only to the extent that clonidine lowered norepinephrine levels and blood pressure compared with placebo. Thus, no interaction was found between the cardiovascular effects of the two drugs. Clonidine did not affect the psychotropic effects or pharmacokinetics of MDMA. The lack of an interaction of the effects of clonidine and MDMA indicates that vesicular release of norepinephrine, which is inhibited by clonidine, does not critically contribute to the effects of MDMA in humans. Although clonidine may be used in the treatment of stimulant-induced hypertensive reactions, the present findings do not support a role for α₂-adrenergic receptor agonists in the prevention of psychostimulant dependence.
Comparable studies
Other randomized controlled trials on MDMA, most cited first.
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- Duloxetine Inhibits Effects of MDMA (“Ecstasy") In Vitro and in Humans in a Randomized Placebo-Controlled Laboratory Study PLoS One May 4, 2012
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Cites 17
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- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
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- The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Proceedings of the National Academy of Sciences March 1, 1992
- The Norepinephrine Transporter Inhibitor Reboxetine Reduces Stimulant Effects of MDMA (“Ecstasy”) in Humans Clinical Pharmacology & Therapeutics June 15, 2011
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