The Journal of pharmacology and experimental therapeuticsJan 13, 2005

How energy loss in muscle cells may contribute to muscle overheating and damage caused by MDMA

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 5, 2026

Abstract

Rats treated with MDMA (40 mg/kg) had a significant increase in serum creatine kinase levels, reaching 955 +/- 132 IU/l compared to 373.2 +/- 59 IU/l in saline-treated controls.

MDMA use is associated with life-threatening conditions such as hyperthermia and rhabdomyolysis.
Evidence suggests that skeletal muscle uncoupling proteins may play a role in MDMA-mediated hyperthermia.
MDMA treatment resulted in a 15% reduction in beta-ATP signal areas and an 88% increase in inorganic phosphate levels.
In vitro and ex vivo experiments showed no direct uncoupling of oxidative phosphorylation in skeletal muscle mitochondria following MDMA treatment.
The presence of uncoupling protein-3 was observed in L6 myotubules, but no direct effects of MDMA on cellular creatine kinase concentrations were found.

Simplified

Use of the popular club drug ecstasy (3,4-methylenedioxymethamphetamine, MDMA) can result in life-threatening hyperthermia and rhabdomyolysis. Recent studies show a link between skeletal muscle uncoupling proteins in MDMA-mediated hyperthermia. The mechanisms by which MDMA interacts with skeletal muscle mitochondria are largely unknown. The present study was designed to comprehensively evaluate the effects of MDMA on bioenergetics and toxicity of skeletal muscle. Using (31)P nuclear magnetic resonance (NMR) and serum creatine kinase levels, we demonstrate evidence for uncoupling of oxidative phosphorylation in the skeletal muscle of MDMA (40 mg/kg)-treated rats. In vivo, rats treated with MDMA had significantly elevated serum creatine kinase levels, a marker of rhabdomyolysis, 4 h post-MDMA treatment (955 +/- 132 IU/l) compared with saline-treated controls (373.2 +/- 59 IU/l). beta-ATP signal areas after MDMA treatment showed significant reductions (15%) from the baseline values with corresponding increases in inorganic phosphate (88% increases) and decreases in intracellular pH. Clark electrode experiments on isolated skeletal muscle mitochondria in vitro (1-5 mM MDMA) and ex vivo in MDMA-treated animals demonstrated no evidence of uncoupling of oxidative phosphorylation. In vitro experiments using L6 myotubules cocultured with primary hepatocytes demonstrated the presence of uncoupling protein-3 in the L6 myotubules, but no evidence of a direct effect of MDMA or its potential metabolites on cellular creatine kinase concentrations. These findings suggest that MDMA uncouples skeletal muscle mitochondria in vivo but that this uncoupling is the result of indirect mechanisms.

Full Text

Full text is available at the source.

View Full Text ↗

How energy loss in muscle cells may contribute to muscle overheating and damage caused by MDMA

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the psychedelic science brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the psychedelic science brief