Heavy users of ecstasy, a synthetic drug that is structurally similar to methamphetamine and the hallucinogen mescaline, may be risking brain damage that remains long after the high has worn off, according to NIDA-supported research.

In a series of studies conducted with rats and nonhuman primates, Dr. George Ricaurte and his colleagues at Johns Hopkins Medical Institutions first determined that a single dose of MDMA, only slightly higher than the size of doses taken by humans, significantly damaged brain cells called neurons that produce serotonin. Serotonin is a major neurotransmitter, or chemical messenger, in the brain that is thought to influence mood, appetite, sleep, and other important functions.

Then Dr. Ricaurte reported that 12 to 18 months after the brains of squirrel monkeys had been damaged by MDMA, serotonin-producing nerve fibers had regrown abnormally in some brain regions and failed to regrow at all in others.

Unlike methamphetamine, which damages brain neurons that produce both serotonin and another important chemical messenger called dopamine, "MDMA selectively damages serotonin neurons in virtually all species examined to date," Dr. Ricaurte says.

Dr. Ricaurte's studies have found that MDMA damages serotonin-producing neurons in the brains of nonhuman primates. The illustration on the left shows a normal neuron. The shaded area in the middle illustration shows the axon terminals of the neuron that are damaged by MDMA. The illustration on the right shows how, 12 to 18 months after being damaged by MDMA, serotonin-producing nerve fibers have regrown excessively in some areas and not at all in others.

"With MDMA, the doses that people take very closely approach the doses known to produce neurotoxic effects in animals," Dr. Ricaurte says.

"At this point, the major question is whether the neuronal changes we see in animals from methamphetamine and MDMA exposure occur in human beings who use these drugs," he says.