MDMA Likes It Hot

X and ambient air temperature.

One of the enduring mysteries about MDMA, the popular amphetamine derivative known as Ecstasy, or X, is the relationship between the drug and ambient air temperature. Why are raves hot, sweaty, and full of loud music and flashing lights? Because “human subjects report a higher euphoric state when taking the drug in sensory rich environments,” according to researchers. So there’s a reason for all those glow sticks and speaker stacks. But is it something inherent in the mechanism of the drug—or simply the overheated party atmosphere combined with vigorous dancing—that can sometimes raise a ravers’ body temperature to dangerous levels?

Drug researchers have known for some time that Ecstasy and high temperature are somehow interlinked. Animal studies have produced strong evidence that a heated environment can cause an increase in MDMA-stimulated serotonin 5-HT response. Many ravers take steps to prevent hyperthermia, or overheating, by regularly drinking water and coming off the dance floor at regular intervals. Most people have heard of hypothermia, a condition in which body temperature drops to dangerously low levels. But hyperthermia can be just as deadly, and it is a common emergency room complaint in MDMA admissions. 

In animal models, rats on MDMA (they like it enough to self-administer) show significantly elevated responses to serotonin in the nucleus accumbens at high room temperatures. What does that mean? What goes up must come down: It opens the door to possible serotonin depletion, which can cause dysfunctions in mood and cognition. Researchers at the University of Texas in Austin have found that in rodents, “the magnitude of the hyperthermic response has been tightly correlated with MDMA-induced 5-HT depletion in various brain regions.” The question they pose is whether “elevated ambient temperatures, such as those encountered in rave venues, can exacerbate MDMA-induced temperature-increasing effects and the likelihood of adverse drug effects.” (Cocaine has temperature-related effects as well. When the ambient air temperature is higher than 75 degrees F, accidental cocaine overdoses increase.)

Ecstasy boosts dopamine as well. The Texas researchers suggest that “the combined enhancement of 5-HT and dopamine may contribute to MDMA’s unique effects on thermoregulation.” They also found that core temperature responses appeared to be “experience-dependent,” meaning that rats didn’t show significantly elevated core temperatures in warm rooms until after they had rolled with MDMA at least ten times. And the worse it gets, the worse it gets, according to the report, published in European Neuropsychopharmacology: “Our results suggest that a heated environment facilitates MDMA-induced disruption of homeostatic thermoregulatory responses, but that repeated exposure to MDMA may also disrupt thermoregulation regardless of ambient temperature.”

So, while all that sweaty dancing amps up the perceptual effects of Ecstasy, it isn’t necessarily implicated in overheating. To simulate a nightclub full of X-ed out ravers, investigators at the Scripps Research Institute tested rats on MDMA while the animals exercised on activity wheels.  Writing in Pharmacology Biochemistry and Behavior, the researchers found that “wheel activity did not modify the hyperthermia produced…. These results suggest that nightclub dancing in the human Ecstasy consumer may not be a significant factor in medical emergencies.”

Bottom line: Although we have a reasonable idea of how it works in animals, we don’t really know how much of that knowledge applies to humans in rave settings. Research aimed at teasing out the specifics of temperature-related responses to MDMA is ongoing. And it does matter. Frequent heat-induced responses could lead to prolonged 5-HT depletion, which is suspected of causing an escalation of drug intake in experienced Ecstasy users. And frequent, escalating use of MDMA is implicated in a long roster of potential cognitive impairments. 

Photo Credit: http://electricchildren.com