Researchers at Johns Hopkins have found that doses of the popular recreational drug Ecstasy similar to those that young adults typically take during all-night dance parties cause extensive damage to brain dopamine neurons in nonhuman primates. Brain dopamine cells help control movement, emotional and cognitive responses, and the ability to feel pleasure, according to the study, published in the Sept. 27 issue of Science. The findings may also shed light on the mechanisms by which Ecstasy damages brain cells.

"The most troubling implication of our findings is that young adults using Ecstasy may be increasing their risk for developing parkinsonism, a condition similar to Parkinson's disease, as they get older," said George A. Ricaurte, associate professor of neurology at the School of Medicine and lead author of the study.

Parkinsonism occurs when brain dopamine neurons are damaged beyond a certain threshold, resulting in a 90 percent or greater loss of brain dopamine, Ricaurte explained. The new findings raise concern that if Ecstasy damages brain dopamine neurons in humans, as it does in monkeys, parkinsonism could develop years after taking the drug because brain dopamine declines with advancing age, Ricaurte said.

"The lack of obvious immediate harmful effects of Ecstasy is partly responsible for the widely held belief that the drug is safe," Ricaurte said. "But people should be aware that the use of Ecstasy in doses similar to those used in recreational settings can damage brain cells, and this damage can have serious effects."

Ricaurte added that the patterns of Ecstasy use have changed since the 1980s, when the drug was taken primarily on college campuses and individuals typically took one or two doses twice monthly. More recently, many individuals take several sequential doses of the drug over the course of a single night. The new study was part of ongoing efforts to further evaluate the neurotoxic risks posed by Ecstasy to humans, Ricaurte said.

To measure the adverse effects of Ecstasy, also known as MDMA or 3,4-methylene-dioxymethamphetamine, the researchers gave squirrel monkeys three sequential doses of Ecstasy at three-hour intervals. Following this regimen, which is similar to that used by recreational Ecstasy users at all-night parties, they found that in addition to serotonin deficits, which the drug has been known to cause for some time, the monkeys unexpectedly developed severe, long-lasting brain dopamine deficits.

Then, using a variety of techniques to look at a region of the brain called the striatum, they found that 60 percent to 80 percent of the dopaminergic nerve endings were destroyed. To determine if these results were unique to squirrel monkeys, the researchers performed the experiments with baboons and obtained similar findings of neuronal injury.

"We do not yet know if our findings in nonhuman primates will generalize to human beings, but, needless to say, this is a major concern," Ricaurte said.

"The message seems clear," Ricaurte added. "The neurotoxic potential of MDMA is high, and use of several sequential recreational doses could have serious long-term consequences."

Glen R. Hanson, acting director of the National Institute on Drug Abuse, said, "This study underscores the need for more research about the extent and nature of the damage that Ecstasy may cause. Clearly, the implications of these findings are cause for concern and should serve as a warning to those thinking about using Ecstasy."

Other authors of the study are Jie Yuan, George Hatzidimitriou, Branden J. Cord and Una D. McCann, all from Johns Hopkins. The study was funded by the U.S. Public Health Service.

Related Web sites
Behavioral Pharmacology Research Unit at Johns Hopkins
'Science' magazine