The role of monoamines in the changes in body temperature induced by 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy) and its derivatives
British Journal of Pharmacology – March 03, 2010
Source: OpenAlex
Summary
MDMA, commonly known as ecstasy, can lead to dangerous body temperature fluctuations, notably hyperthermia, which may be fatal. In laboratory studies with rats, MDMA induced hyperthermia and hypothermia depending on environmental conditions. Specifically, neurotransmitters like serotonin, dopamine, and norepinephrine play critical roles in these responses. Notably, 5-HT receptors modulate hyperthermia but do not directly cause it. Effective management relies on cooling techniques rather than pharmaceutical interventions, emphasizing the importance of educating users about hyperthermia risks and environmental control for safety.
Abstract
Hyperthermia is probably the most widely known acute adverse event that can follow ingestion of 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy) by recreational users. The effect of MDMA on body temperature is complex because the drug has actions on all three major monoamine neurotransmitters [5‐hydroxytryptamine (5‐HT), dopamine and noradrenaline], both by amine release and by direct receptor activation. Hyperthermia and hypothermia can be induced in laboratory animals by MDMA, depending on the ambient temperature, and involve both central thermoregulation and peripheral changes in blood flow and thermogenesis. Acute 5‐HT release is not directly responsible for hyperthermia, but 5‐HT receptors are involved in modulating the hyperthermic response. Impairing 5‐HT function with a neurotoxic dose of MDMA or p ‐chlorophenylalanine alters the subsequent MDMA‐induced hyperthermic response. MDMA also releases dopamine, and evidence suggests that this transmitter is involved in both the hyperthermic and hypothermic effects of MDMA in rats. The noradrenergic system is also involved in the hyperthermic response to MDMA. MDMA activates central α 2A ‐adrenoceptors and peripheral α 1 ‐adrenoceptors to produce cutaneous vasoconstriction to restrict heat loss, and β 3 ‐adrenoceptors in brown adipose tissue to increase heat generation. The hyperthermia occurring in recreational users of MDMA can be fatal, but data reviewed here indicate that it is unlikely that any single pharmaceutical agent will be effective in reversing the hyperthermia, so careful body cooling remains the principal clinical approach. Crucially, educating recreational users about the potential dangers of hyperthermia and the control of ambient temperature should remain key approaches to prevent this potentially fatal problem.