The effects of ecstasy (MDMA) on rat liver bioenergetics

Daniel E. Rusyniak, Stephany L. Tandy, Lisa M. Kamendulis, Jon E. Sprague, James E. Klaunig

Research output: Contribution to journalArticle

6 Scopus citations


Objectives Use of the drug ecstasy (3,4-methylenedioxymethamphetamine [MDMA]) can result in life-threatening hyperthermia. Agents that uncouple mitochondrial oxidative phosphorylation are known to cause severe hyperthermia. In the present study, the authors tested the hypothesis that MDMA directly uncouples oxidative phosphorylation in rat liver mitochondria. Methods Effects on mitochondrial bioenergetics were assessed both in vitro and ex vivo. In vitro studies consisted of measuring the effects of MDMA (0.1-5.0 mmol/L) on states of respiration in isolated rat liver mitochondria and on mitochondrial membrane potential in a rat liver cell line. In ex vivo studies, mitochondrial rates of respiration were measured in the livers of rats one hour after treatment with MDMA (40 mg/kg subcutaneously). Results With the in vitro mitochondrial preparations, only concentrations of 5 mmol/L MDMA showed evidence of uncoupling with a slight increase in state 4 respiration and a corresponding decrease in the respiratory control index. MDMA (0.1-5.0 mmol/L) failed to decrease the mitochondrial membrane potential in 3,3-dihexyloxacarbocyanide iodide-stained WB-344 cells after either one or 24 hours of incubation. Ex vivo rates of respiration obtained from the livers of rats one hour after treatment with MDMA (40 mg/kg subcutaneously) showed no evidence of mitochondrial uncoupling. Conclusions These data suggest that while high concentrations of MDMA have some mild uncoupling effects in isolated mitochondria, these effects do not translate to cell culture or ex vivo studies in treated animals. These data do not support the view that the hyperthermia induced by MDMA is from a direct effect on mitochondrial oxidative phosphorylation.

Original languageEnglish (US)
Pages (from-to)723-729
Number of pages7
JournalAcademic Emergency Medicine
Issue number7
StatePublished - Jul 2004


  • 3,4-methylenedioxymethamphetamine
  • amphetamines
  • liver
  • mitochondria
  • oxidative phosphorylation
  • uncoupling agents

ASJC Scopus subject areas

  • Emergency Medicine

Fingerprint Dive into the research topics of 'The effects of ecstasy (MDMA) on rat liver bioenergetics'. Together they form a unique fingerprint.

  • Cite this

    Rusyniak, D. E., Tandy, S. L., Kamendulis, L. M., Sprague, J. E., & Klaunig, J. E. (2004). The effects of ecstasy (MDMA) on rat liver bioenergetics. Academic Emergency Medicine, 11(7), 723-729.