Results of a new preclinical study from the National Institutes of Health - published in the Journal of Neuroscience - find that the recreational drug MDMA, in combination with warmer brain temperature, is associated with a higher risk of death.
High doses of MDMA (more commonly known as ecstasy when it is delivered in pill form, or "Molly" when it is taken as a powder) can increase body temperature and cause various adverse effects.
Previous studies have suggested that ecstasy users experience a shrinking of their hippocampal volume and a reduction in grey matter.
These changes in brain structure may be responsible for the significant memory problems reported by chronic users of the drug, as hippocampal atrophy is a hallmark for cognitive impairment diseases such as Alzheimer's.
Studies looking at the effects of moderate doses of the drug have reported inconsistent findings. Consequently, some people assume the drug to be harmless if it is taken in moderation. The new study - designed to mimic the conditions in which MDMA is typically taken - challenges that assumption, however.
The scientists administered MDMA to rats in moderate to low doses that have been shown in previous studies not to be fatal. The rats were monitored for changes in brain and body temperature, and the scientists measured how well the rats' blood vessels were able to dilate when their bodies attempt to cool themselves.
'Rats lost ability to eliminate excessive heat when in warmer environment'
The researchers found that, when the rats were alone and in a room-temperature environment, a moderate dose of MDMA modestly increased both brain and body temperature. The rats' ability to eliminate excessive heat was also modestly impaired.
But when the same dose of MDMA was administered to rats that were in the presence of another rat in their cage, or when they were in a warmer environment, the researchers found that some rats died.
The rats died because the natural ability of their bodies to eliminate heat had been diminished by the drug.
People often take MDMA in hot, crowded, social settings, so these findings could also be relevant to humans.
Some people assume MDMA to be harmless if it is taken in moderation. The new study - designed to mimic the conditions in which the drug is typically taken - challenges that assumption, however.
"These results demonstrate that the use of MDMA in certain warm, social settings could be more dangerous than commonly believed," says Dr. Eugene Kiyatkin, first author on the study.
"Even with moderate doses, we saw drug-induced, fatal brain hyperthermia during conditions of social interaction and in warm environments."
The researchers suggest that these findings could lead to medical interventions to counter the development of MDMA-induced hyperthermia. For instance, a treatment that targeted the constrictions of blood vessels in the skin would increase the efficiency of whole-body cooling, potentially saving lives.
In March, researchers at the Los Angeles Biomedical Research Institute announced a study into the safety and effectiveness of MDMA-assisted therapy for social anxiety in adults with autism.
That study is the latest in a program of research assessing the therapeutic applications of MDMA for people who have autism. The reason why researchers have turned to MDMA as a treatment for this group is because the conventional prescription medication used to treat anxiety or depression in other adults is often ineffective in people who have autism.
In fact, MDMA was first developed as a psychiatric therapy, by the Merck pharmaceutical company in 1912 - when it was simply known as "3,4-methylenedioxymethamphetamine." It was not until 1985 that therapeutic use of MDMA was criminalized, as a result of widespread recreational use.