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October 30, 1998

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Hopkins Study Shows Brain Damage Evidence In "Ecstasy" Users

The common street drug "ecstasy" causes brain damage in people, according to a new Johns Hopkins study. In a report in The Lancet released this week, Hopkins scientists show that the drug -- known chemically as MDMA -- damages specific nerves in the brain that release serotonin, the nerve transmitter thought to play a role in regulating mood, memory, pain perception, sleep, appetite and sexual activity.

"We had long suspected MDMA was dangerous, based on our earlier studies in primates that showed nerve damage at doses similar to those taken by recreational drug users," says neurologist George Ricaurte, M.D., Ph.D., who led the research team. Additional studies by the team examined drug users' spinal fluid for levels of a serotonin by product; reduced amounts strongly suggested brain damage in humans.

"But this is the first time we've been able to examine the actual serotonin-producing nerve cells directly in the brain," Ricaurte says. Using a nerve-specific technique that took more than five years to develop, the scientists took PET scans of 14 men and women who reported heavy use of ecstasy. With a radio-labeled probe, the team targeted molecules -- serotonin transporters -- that normally reabsorb serotonin into nerve cells after it has done its job.

Like certain antidepressants, MDMA also attaches to serotonin transporters. The transporters lie embedded in the membranes of nerve cells, at the tips of fingerlike extensions called axons.

In the study, the PET scans showed MDMA users had far fewer serotonin transporters than controls who didn't use the drug. Also, the greater the use of MDMA -- some of the subjects had used it 200 or more times -- the greater the loss. "These losses are significant, and, along with our early studies in animals, suggest that nerve cells are damaged," says Ricaurte. Whether or not the cells are permanently damaged, he says, is uncertain. But in studies in animals, including primates, the losses are long-lasting and may be permanent in some brain regions.

The area of brain damage is diffuse but involves the endings of serotonin-releasing nerves that reach throughout the forebrain -- the "higher" brain that includes the cerebral cortex and adjacent areas, parts of the brain involved in thought, memory and emotion.

Ecstasy is a designer drug hybrid of the hallucinogen mescaline and the stimulant amphetamine. Users report a heightened sense of closeness with others, increased awareness of emotion and ability to communicate.

"They find these effects unique," says Ricaurte, "and we hope to use this new technique to explore the basis for good feelings, as well as for depression and anxiety. But our immediate concern is that people who use MDMA recreationally are unwittingly putting themselves at risk of developing brain injury."

As for direct behavioral signs of brain damage in heavy users of the drug, Ricaurte says, studies to evaluate possible differences in thought and behavior are well under way. "We have some early indications there may be changes in memory and cognition."

The PET technique in this study is the first that allows researchers to pick serotonin-producing nerves out of millions of others in the brain and view them directly, says Ricaurte. The team is already looking into applications of the method to study depression and Parkinson's disease.

Ecstasy is especially popular at "raves," the late-night, music-driven parties that attract hundreds of young adults.

Other researchers on the team are Robert Dannals, Ph.D., Ursula Scheffel, Ph.D., and Zsolt Szabo, M.D., Ph.D., of Hopkins; and Una McCann, Ph.D., of the National Institute of Mental Health (NIMH).

Funding for the study was from the National Institute on Drug Abuse.


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