Effects of MDMA on body temperature in humans

Abstract

Hyperthermia is a severe complication associated with the recreational use of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy). In this review, the clinical laboratory studies that tested the effects of MDMA on body temperature are summarized. The mechanisms that underlie the hyperthermic effects of MDMA in humans and treatment of severe hyperthermia are presented. The data show that MDMA produces an acute and dose-dependent rise in core body temperature in healthy subjects. The increase in body temperature is in the range of 0.2-0.8°C and does not result in hyperpyrexia (>40°C) in a controlled laboratory setting. However, moderately hyperthermic body temperatures >38.0°C occur frequently at higher doses, even in the absence of physical activity and at room temperature. MDMA primarily releases serotonin and norepinephrine. Mechanistic clinical studies indicate that the MDMA-induced elevations in body temperature in humans partially depend on the MDMA-induced release of norepinephrine and involve enhanced metabolic heat generation and cutaneous vasoconstriction, resulting in impaired heat dissipation. The mediating role of serotonin is unclear. The management of sympathomimetic toxicity and associated hyperthermia mainly includes sedation with benzodiazepines and intravenous fluid replacement. Severe hyperthermia should primarily be treated with additional cooling and mechanical ventilation.

Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction

“…Human reports suggest that labetalol taken before MDMA exposure decrease MDMA-induced hyperthermia (Liechti, 2014), but in our hands this drug was ineffective and had minimal, if any, effects on all temperature parameters. The reasons for the differences between carvedilol and labetalol are unclear and may be due to their different affinities for the various subgroups of alpha-and beta-adrenoceptors (Ruffolo et al, 1990).…”

“…Variability in temperature responses may explain the large individual differences in the emergence of adverse psychological and cognitive symptoms seen in some longterm MDMA users (for review, see Parrott, 2013b). Therefore, despite the modest hyperthermic responses to MDMA seen in humans under standard laboratory conditions (Freedman et al, 2005;Liechti, 2014), and its potential as a therapeutic agent for post-traumatic stress disorder (Mithoefer et al, 2011(Mithoefer et al, , 2013, our study underscores the possible dangers of 'recreational' MDMA use.…”

“…This treatment protocol allowed us to compare the effectiveness of each drug in terms of the onset of its therapeutic action, strength, and duration. All drugs tested in this study are FDA-approved, currently used to treat chronic diseases in humans, and have previously been shown to decrease MDMA-induced body hyperthermia under standard laboratory conditions (Blessing et al, 2003;Sprague et al, 2005;Hysek et al, 2012;Liechti, 2014).…”

“…The temperature effects of MDMA are relatively modest when the drug is administered to humans or animals under standard laboratory conditions (Mechan et al, 2002;Freedman et al, 2005;Liechti, 2014), but are strongly potentiated under conditions of high activity, social interaction, and warm ambient temperature (Gordon et al, 1991;Brown and Kiyatkin, 2004;Parrott, 2012). This state-dependent modulation of MDMA-induced hyperthermia renders MDMA much more dangerous when used during 'rave parties' or crowded events, both of which are associated with intense social interaction, increased physical activity, emotional engagement, and typically take place in warm, humid environments that diminish heat loss from body surfaces (Kalant, 2001;Parrott and Young, 2014).…”

“…MDMAinduced hyperthermia can be life-threatening and current strategies for treatment, such as whole-body cooling, replenishment of water, and sedation with benzodiazepine tranquillizers, are merely palliative (Liechti, 2014). Therefore, there is a clear clinical need for pharmacological interventions to rapidly alleviate MDMA-induced hyperthermia in emergency room situations.…”