Duloxetine inhibits effects of MDMA ("ecstasy") in vitro and in humans in a randomized placebo-controlled laboratory study.

Hysek CM, Simmler LD, Nicola VG, Vischer N, Donzelli M, Krähenbühl S, Grouzmann E, Huwyler J, Hoener MC, Liechti ME
PLoS One. 2012 7 (5): e36476

PMID: 22574166 · PMCID: PMC3344887 · DOI:10.1371/journal.pone.0036476

UNLABELLED - 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.

MeSH Terms (15)

3,4-Methylenedioxyamphetamine Adult Biological Transport Duloxetine Hydrochloride Female Humans Laboratories Male N-Methyl-3,4-methylenedioxyamphetamine Norepinephrine Placebo Effect Receptors, Adrenergic Serotonin Serotonin Plasma Membrane Transport Proteins Thiophenes

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