Thermoregulatory effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans

Rationale: Although 3,4-methylenedioxymeth-amphetamine (MDMA; Ecstasy) has been reported to cause fatal hyperthermia, few studies of the effects of MDMA on core body temperature in humans have been conducted demonstrating increased body temperature. In rats, MDMA causes hyperthermia at warm ambient temperatures but hypothermia at cold ones. Objectives: In this study, the physiological and subjective effects of MDMA in humans were determined at cold (18 degrees C) and warm (30 degrees C) ambient temperatures in a temperature and humidity-controlled laboratory. Methods: Ten healthy volunteers who were recreational users of MDMA were recruited. Four laboratory sessions were conducted in a 2x2 design [i.e., two sessions at 30 degrees C and two at 18 degrees C, two during MDMA (2 mg/kg, p.o.) and two during placebo, in double-blind fashion]. Core body temperature (ingested radiotelemetry pill), skin temperature (four weighted sites), heart rate, blood pressure, metabolic rate (indirect calorimetry), shivering (electromyogram levels), and sweat rate (capacitance hygrometry) were measured as well as subjective effects for several time periods following capsule ingestion. Results: MDMA produced significant elevations in core body temperature and metabolic rate in both warm and cold conditions. MDMA also produced significant elevations in blood pressure and heart rate and significantly increased several ratings of subjective effects similar to those previously reported. There were no differences related to ambient temperature for any of the subjective effects, except that ratings of cold and warm were appropriate to the ambient temperature and were not influenced by MDMA. Conclusions: Unlike findings in rats, MDMA increased core body temperature regardless of ambient temperature in humans. These increases appeared related to increases in metabolic rate, which were substantial. These findings warrant further investigations on the role of MDMA and other stimulants in altering metabolism and thermogenesis.