title: Duloxetine inhibits effects of MDMA ("ecstasy") in vitro and in humans in a randomized placebo-controlled laboratory study.
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.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00990067.
authors.affiliation: Psychopharmacology Research Group, Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
authors.forename: Cédric M
authors.initials: CM
authors.lastname: Hysek
authors.forename: Linda D
authors.initials: LD
authors.lastname: Simmler
authors.forename: Valentina G
authors.initials: VG
authors.lastname: Nicola
authors.forename: Nerina
authors.initials: N
authors.lastname: Vischer
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Donzelli
authors.forename: Stephan
authors.initials: S
authors.lastname: Krähenbühl
authors.forename: Eric
authors.initials: E
authors.lastname: Grouzmann
authors.forename: Jörg
authors.initials: J
authors.lastname: Huwyler
authors.forename: Marius C
authors.initials: MC
authors.lastname: Hoener
authors.forename: Matthias E
authors.initials: ME
authors.lastname: Liechti
mesh_terms: D015104:3,4-Methylenedioxyamphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D007753:Laboratories; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000378:metabolism; D015990:Placebo Effect; D011941:Receptors, Adrenergic / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D013876:Thiophenes / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D011941:Receptors, Adrenergic; D050486:Serotonin Plasma Membrane Transport Proteins; D013876:Thiophenes; D012701:Serotonin; D015104:3,4-Methylenedioxyamphetamine; D000068736:Duloxetine Hydrochloride; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009638:Norepinephrine