Duloxetine inhibits effects of MDMA ("ecstasy") in vitro and in humans in a randomized placebo-controlled laboratory study
Cédric M Hysek, Linda D Simmler, Valentina G Nicola, Nerina Vischer, Massimiliano Donzelli, Stephan Krähenbühl, Eric Grouzmann, Jörg Huwyler, Marius C Hoener, Matthias E Liechti, Cédric M Hysek, Linda D Simmler, Valentina G Nicola, Nerina Vischer, Massimiliano Donzelli, Stephan Krähenbühl, Eric Grouzmann, Jörg Huwyler, Marius C Hoener, Matthias E Liechti
Abstract
This study assessed the effects of the serotonin (5-HT) and norepinephrine (NE) transporter inhibitor duloxetine on the effects of 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy) in vitro and in 16 healthy subjects. The clinical study used a double-blind, randomized, placebo-controlled, four-session, crossover design. In vitro, duloxetine blocked the release of both 5-HT and NE by MDMA or by its metabolite 3,4-methylenedioxyamphetamine from transmitter-loaded human cells expressing the 5-HT or NE transporter. In humans, duloxetine inhibited the effects of MDMA including elevations in circulating NE, increases in blood pressure and heart rate, and the subjective drug effects. Duloxetine inhibited the pharmacodynamic response to MDMA despite an increase in duloxetine-associated elevations in plasma MDMA levels. The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA. Duloxetine may be useful in the treatment of psychostimulant dependence.
Trial registration: Clinicaltrials.gov NCT00990067.
Conflict of interest statement
Competing Interests: One of the authors (MCH) is employed by a commercial company (Hoffmann-La Roche Ltd.). This does not alter the authors’ adherence to all the PLoS ONE policies on sharing data and materials.
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References
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