Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction.
Eugene A. Kiyatkin, Suelynn E Ren, Ken T. Wakabayashi, Michael H Baumann, Yavin Shaham
Neuropsychopharmacology January 2016 DOI: 10.1038/npp.2015.182 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal experiment Peer reviewed |
|---|---|
| Population | Rats injected with MDMA during social interaction |
| Interventions | MDMA Carvedilol Labetalol Clozapine |
| Dose | 9 mg/kg MDMA |
| Topics | MDMA |
| Key findings | Clozapine produced a marked, immediate reversal of MDMA-induced brain and body hyperthermia by inhibiting brain metabolic activation and blocking skin vasoconstriction, whereas carvedilol was only modestly effective and labetalol was ineffective. The authors suggest clozapine and related centrally acting drugs might be highly effective for reversing MDMA-induced hyperthermia in emergency clinical situations. |
Abstract
MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 4
- Dantrolene sodium fails to reverse robust brain hyperthermia induced by MDMA and methamphetamine in rats. Psychopharmacology April 1, 2023
- Synthetic Drugs and Behavioural Addictions: LSD, MDMA and Digital Toxicity June 1, 2026
- Hard Boiled: Alcohol Use as a Risk Factor for MDMA-Induced Hyperthermia: a Systematic Review. Neurotoxicity Research December 2021
- MDMA, Methylone, and MDPV: Drug-Induced Brain Hyperthermia and Its Modulation by Activity State and Environment. Current Topics in Behavioral Neurosciences 2017
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