The effects of fluoxetine on the subjective and physiological effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans

Psychopharmacology (Berl). 2007 Jan;189(4):565-73. doi: 10.1007/s00213-006-0576-z. Epub 2006 Oct 18.


Objective: The purpose of this study was to investigate the role of serotonin (5-HT) in the effects of oral 3,4-methylenedioxymethamphetamine (MDMA) in humans.

Materials and methods: The subjective and physiological effects of 1.5 mg/kg MDMA were evaluated after 20 mg fluoxetine in eight recreational MDMA users in a double-blind, placebo-controlled study. During phase 1, participants were maintained on placebo for at least 5 days and tested with MDMA and placebo on separate sessions. In phase 2, the procedure was the same except fluoxetine was administered daily for at least 5 days. During sessions, placebo or fluoxetine was given 1 h before the session drug and effects were measured over the next 7 h.

Results: MDMA increased positive-like subjective effects on all the Addiction Research Center Inventory scales; Arousal, Elation, Positive Mood, and Vigor on the Profile of Mood States; Drug Liking, Friendly, Good Drug Effect, High, Stimulated, and Talkative on the Visual Analog Scale; and End-of-Session Liking and Crossover Point on the Multiple Choice Procedure. MDMA also increased measures of anxiety. On the Hallucinogenic Rating Scale, all scales except Volition were increased. MDMA also increased blood pressure and heart rate. Fluoxetine treatment attenuated most of the positive-like subjective effects including the Affect and Soma scales of the Hallucinogen Rating Scale. In addition, heart rate but not blood pressure increases were reduced.

Conclusions: These results suggest that blockade of 5-HT reuptake by fluoxetine can dampen the effects of MDMA and further supports the role of 5-HT in its behavioral effects in humans.

Publication types

  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Affect / drug effects
  • Behavior / drug effects*
  • Blood Pressure / drug effects
  • Cardiovascular Physiological Phenomena / drug effects*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Interactions
  • Female
  • Fluoxetine / pharmacology*
  • Hallucinogens / pharmacology
  • Heart Rate / drug effects
  • Humans
  • Male
  • Mental Processes / drug effects
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
  • Serotonin Agents / pharmacology*
  • Serotonin Uptake Inhibitors / pharmacology*


  • Hallucinogens
  • Serotonin Agents
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • N-Methyl-3,4-methylenedioxyamphetamine