Agony of Ecstacy Includes Extensive Neural Damage

The illegal drug Ecstasy heightens sensations, gives a euphoric rush, reduces anxiety, and increases sensitivity to others. So it’s no wonder that so many American youth are enamored of it.

But the price they are paying for even one “Ecstatic” night might be high, a new nonhuman primate study suggests. The price is substantial damage to brain neurons that use either the neurotransmitter serotonin or the neurotransmitter dopamine, especially the latter.

The study was conducted by George Ricaurte, M.D., an associate professor of neurology at Johns Hopkins University School of Medicine, and colleagues. Results from the study appeared in the September 27 Science.

Ricaurte and his colleagues wanted to evaluate the neurotoxic potential of Ecstasy (officially known as 3,4-methylenedioxymethamphetamine, or MDMA) when it is consumed at a typical all-night Ecstasy party. So they injected five squirrel monkeys with an Ecstasy dosage of 2 mg/kg three different times at three-hour intervals, for a total dose of 6 mg/kg.

Three of the five monkeys tolerated the drug without any apparent difficulty. The fourth monkey became less mobile and had an unstable, tentative gait after the second dose and therefore was not given the third planned dose. The fifth monkey developed hyperthermia—one of the main side effects of Ecstasy—and died within hours of receiving the last dose of the drug.

Two weeks later, the brains of the three monkeys that had received Ecstasy were then compared with the brains of the three control monkeys to determine what effects Ecstasy had had on the former. The Ecstasy-exposed brains were found to have a reduction in axons of neurons that use the neurotransmitter serotonin, as well as a reduction in axons of neurons that use the neurotransmitter dopamine. Axon reduction in dopaminergic neurons was especially noticeable.

The researchers then repeated their experiment on baboons to see whether their findings were unique to squirrel monkeys. They were not, they found. Again Ecstasy produced extensive loss of axons in both serotonergic neurons and dopaminergic neurons, especially the latter.

“These findings suggest that humans who use repeated doses of MDMA over several hours are at high risk for incurring severe brain dopaminergic neural injury (along with significant serotonergic neurotoxicity),” the investigators concluded in their study report. “This injury, together with the decline in dopaminergic function known to occur with age, may put these individuals at increased risk for developing Parkinsonism and other neuropsychiatric diseases involving brain dopamine/serotonin deficiency, either as young adults or later in life.”

Glen Hanson, Ph.D., D.D.S., acting director of the National Institute on Drug Abuse, was quoted in a Johns Hopkins press release as saying, “Clearly, the implications of these findings are cause for concern and should serve as a warning to those thinking about using Ecstasy.”

Some other scientists have also conducted nonhuman primate studies to explore the impact of Ecstasy on the brain. They too found damage to neurons that use serotonin, but not to neurons that use dopamine. The reason they did not find any damage to dopaminergic neurons, Ricaurte and his team believe, may be because those researchers followed a more spaced-out dosing schedule than they had.

The study was funded by U.S. Public Health Service grants.

The study, “Severe Dopaminergic Neurotoxicity in Primates After a Common Recreational Dose Regimen of MDMA (‘Ecstasy’),” is posted on the Web at www.sciencemag.org/cgi/content/full/297/5590/2260. ▪

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