mdma hyperthermia

Introduction

Hyperthermia is a severe and potentially fatal complication associated with the recreational use of 3,4-methylenedioxymethamphetamine (MDMA, commonly known as Ecstasy). This condition results from a complex interplay of various physiological mechanisms, including neurotransmitter release and thermoregulatory processes. Understanding these mechanisms is crucial for developing effective treatments and preventive measures.

Key Insights

Adrenergic Receptors and Hyperthermia:
- Carvedilol, an α1 and β3-adrenergic receptor antagonist, can prevent and reverse MDMA-induced hyperthermia, suggesting these receptors play a significant role in the thermogenic response .
Serotonin and Dopamine Involvement:
- MDMA-induced hyperthermia is primarily driven by dopamine release acting on D1 receptors, rather than serotonin release .
- Serotonin uptake inhibitors do not significantly alter MDMA-induced hyperthermia, indicating a lesser role for serotonin in this response .
Gut Microbiome Influence:
- The gut microbiome significantly influences MDMA-induced hyperthermia. Antibiotic treatment that reduces gut bacteria attenuates the hyperthermic response, highlighting a potential role for gut microbiota in thermoregulation.
Environmental and Physiological Factors:
- Ambient temperature and housing conditions significantly affect the severity of MDMA-induced hyperthermia. Higher ambient temperatures exacerbate the hyperthermic response, which is critical in settings like crowded dance clubs .
- The hypothalamic-pituitary-thyroid axis and sympathetic nervous system are involved in MDMA-induced hyperthermia, with α1 and β3-adrenergic receptors playing distinct roles in core and skeletal muscle temperature regulation.
Sex Differences:
- Female subjects are less sensitive to MDMA-induced hyperthermia compared to males. This difference is attributed to lower sympathetic activation, reduced vascular sensitivity to α1-adrenergic stimulation, increased sensitivity to nitric oxide, and lower skeletal muscle UCP3 expression in females.
Clinical Observations in Humans:
- In humans, MDMA causes a dose-dependent rise in core body temperature, primarily through norepinephrine release, enhanced metabolic heat generation, and cutaneous vasoconstriction, which impairs heat dissipation .

Conclusion

MDMA-induced hyperthermia is a multifaceted condition influenced by adrenergic receptor activity, dopamine release, gut microbiota, environmental factors, and sex differences. Effective management of this condition requires a comprehensive understanding of these mechanisms. Current evidence suggests that targeting adrenergic receptors, particularly with drugs like carvedilol, and considering environmental and physiological factors can be crucial in mitigating the hyperthermic effects of MDMA.

Summary

Introduction

Key Insights

Conclusion

Sources and full results

Carvedilol reverses hyperthermia and attenuates rhabdomyolysis induced by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) in an animal model*

Carvedilol effectively reverses hyperthermia and attenuates rhabdomyolysis induced by MDMA intoxication, warranting further investigation as potential novel therapies for psychostimulant-induced hyperthermia.

The pharmacology of the acute hyperthermic response that follows administration of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) to rats

MDMA-induced hyperthermia in rats may result from increased dopamine release at D1 receptors, not from increased 5HT release.

The influence of the host microbiome on 3,4-methylenedioxymethamphetamine (MDMA)-induced hyperthermia and vice versa

Gut microbiome plays a contributing role in MDMA-induced hyperthermia, and antibiotics can reduce this hyperthermic response in rats.

A review of the mechanisms involved in the acute MDMA (ecstasy)-induced hyperthermic response.

MDMA-induced hyperthermia is primarily caused by dopamine release and is influenced by dose, ambient temperature, and housing conditions, with the size of the acute hyperthermic response determining the severity of subsequent neurotoxicity.

Hypothalamic-Pituitary-Thyroid Axis and Sympathetic Nervous System Involvement in Hyperthermia Induced by 3,4-Methylenedioxymethamphetamine (Ecstasy)

MDMA-induced hyperthermia involves an interaction between the hypothalamic-pituitary-thyroid axis and the sympathetic nervous system, with 1- and 3-adrenergic receptors differentially regulating core and skeletal muscle hyperthermia.

Increased anxiety and "depressive" symptoms months after MDMA ("ecstasy") in rats: drug-induced hyperthermia does not predict long-term outcomes

MDMA-induced hyperthermia does not predict long-term anxiety and cognitive changes in rats, regardless of body temperature at the time of dosing.

Effects of MDMA on body temperature in humans

MDMA increases body temperature in healthy subjects, with severe hyperthermia requiring additional cooling and mechanical ventilation.

Hyperthermia induced by 3,4-methylenedioxymethamphetamine in unrestrained rhesus monkeys.

MDMA induces acute hyperthermia in unrestrained rhesus monkeys, similar to rodents and humans, without increasing locomotor activity, suggesting primates may differ from rodents in thermoregulatory sensitivity.

The role of monoamines in the changes in body temperature induced by 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy) and its derivatives

MDMA's effect on body temperature is complex, with 5HT, dopamine, and noradrenaline neurotransmitters playing a role, and careful body cooling and education are key to prevent fatal hyperthermia.

The hyperthermia mediated by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) is sensitive to sex differences.

Females are less sensitive to the hyperthermic effects of MDMA due to reduced sympathetic activation, less sensitivity to alpha(1)-AR stimulation, increased sensitivity to NO, and less UCP3 expression in skeletal muscle.

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