Brain hyperthermia induced by MDMA (‘ecstasy’): modulation by environmental conditions
Paul Brown, Eugene A. Kiyatkin
European Journal of Neuroscience July 1, 2004 DOI: 10.1111/j.0953-816x.2004.03453.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male rats |
| Intervention | MDMA |
| Dose | 9 mg/kg |
| Topics | MDMA |
| Keywords | Hyperthermia Neurotoxicity Nucleus accumbens Hippocampal formation Hippocampus Pharmacology Anesthesia Endocrinology |
| Citations | 105 |
| Key findings | MDMA-induced brain hyperthermia is strongly potentiated by social interaction and impaired heat dissipation, reaching lethal levels at warm ambient temperatures. |
Abstract
Abstract Drugs of abuse, such as 3,4‐methylenedioxymethamphetamine (MDMA), often have more powerful effects during states of increased activation and under specific environmental conditions. Because hyperthermia is a major complication of MDMA use and a factor potentiating neurotoxicity, we examined the effects of this drug (9 mg/kg, sc; approximately one‐fifth of the known LD 50 in rats) on brain [nucleus accumbens (Nacc) and hippocampus (Hippo)] and muscle (musculus temporalis) temperatures in male rats under conditions that either model human drug use (social interaction with female, warm temperature) or restrict heat dissipation from the brain (chronic occlusion of jugular veins). Under quiet resting conditions at 23 °C, MDMA induced a moderate but prolonged hyperthermia. Both NAcc and Hippo showed more rapid and stronger temperature increases than muscle, suggesting metabolic neural activation as a primary cause of brain hyperthermia. During social interaction with a female, brain hyperthermia induced by MDMA was significantly potentiated (+89%). Brain hyperthermia induced by MDMA was also strongly potentiated (+188%) in animals with chronically occluded jugular veins, suggesting impaired cerebral outflow enhances intrabrain heat accumulation. At 29 °C, MDMA pushed temperatures in the brain to its biological limits (>41 °C; +268%), resulting in fatalities in most (83%) tested animals. Therefore, by inducing metabolic brain activation and restricting heat dissipation, MDMA use under ‘party’ conditions may be much more dangerous than under standard laboratory conditions.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 33
- MDMA in humans: factors which affect the neuropsychobiological profiles of recreational ecstasy users, the integrative role of bioenergetic stress Journal of Psychopharmacology March 1, 2006
- Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine ACS Chemical Neuroscience July 12, 2018
- Pharmacokinetic, Ambulatory, and Hyperthermic Effects of 3,4-Methylenedioxy-N-Methylcathinone (Methylone) in Rats Frontiers in Psychiatry November 17, 2017
- Effects of MDMA on body temperature in humans Temperature October 31, 2014
- A developmental comparison of the neurobehavioral effects of ecstasy (MDMA) Neurotoxicology and Teratology October 21, 2006
and 28 more in the library
Cites 14
- 'Eve' and 'Ecstasy'. A report of five deaths associated with the use of MDEA and MDMA JAMA March 27, 1987
- (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals Neuropsychobiology 2000
- The pharmacology of the acute hyperthermic response that follows administration of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) to rats British Journal of Pharmacology 2002
- 'Eve' and 'Ecstasy' JAMA March 27, 1987
- Stereochemical effects of 3,4-methylenedioxymethamphetamine (MDMA) and related amphetamine derivatives on inhibition of uptake of [3H]monoamines into synaptosomes from different regions of rat brain. Biochemical Pharmacology July 15, 1987
and 9 more in the library