Study confirms low levels of serotonin transporter in cerebral cortex of chronic ecstasy users

Levels of the serotonin transporter are low in the brains of users of ecstasy, according to a US National Institute of Drug Abuse-funded study by Toronto's Centre for Addiction and Mental Health (CAMH) and The Hospital for Sick Children (SickKids) published today in the journal Brain.

Ecstasy (mdma) is a stimulant drug widely used recreationally that is also being tested in clinical trials for the treatment of post-traumatic stress disorder.

Led by Dr. Stephen Kish at CAMH, this study provides confirmation of a previous finding from Johns Hopkins University that levels of the serotonin transporter (SERT) are low in cerebral cortex of chronic ecstasy users. The subjects were "typical" ecstasy users who used about two tablets of the drug twice a month.

SERT is a protein responsible for regulating levels of serotonin, a neurotransmitter important for mood and impulse control. Ecstasy interacts with SERT to cause the release of serotonin, an action that probably explains some of the behavioral effects of the drug such as increased sociability.

Scientists have long suspected that ecstasy might harm brain cells that use serotonin, but 12 years of brain scan studies have produced contradictory results, even within the same laboratory.

The CAMH study used a large subject size (49 drug users, 50 control subjects), confirmed by hair analysis that ecstasy users actually used the drug, and used an imaging probe that could measure SERT throughout the brain.

"We were surprised to discover that SERT was decreased only in the cerebral cortex and not throughout the brain, perhaps because serotonin nerves to the cortex are longer and more susceptible to changes. This finding is almost identical to newer data from Johns Hopkins and is the first time that one laboratory has actually been able to replicate results of another independent laboratory in a SERT study of ecstasy users." said Dr. Kish.

Drug hair analysis indicated that many ecstasy users, probably unknowingly, also used methamphetamine, which might itself damage serotonin cells; however, low SERT was found both in ecstasy users who used and who did not use methamphetamine. Dr. Jason Lerch at SickKids showed that those ecstasy users who also used methamphetamine had a slightly thinner cerebral cortex.

Does low SERT equal "structural brain damage"? "Not necessarily" said co-author Dr. Isabelle Boileau of CAMH. "There is no way to prove whether low SERT is explained by physical loss of the entire serotonin nerve cell, or by a loss of SERT protein within an intact nerve cell."

Dr. Kish suggests that low SERT might explain why many ecstasy users need to keep increasing the dose to experience the same effects, since SERT is necessary for the action of ecstasy. "Most of the ecstasy users of our study complained that the first dose is always the best, but then the effects begin to decline and higher doses are needed. The need for higher doses, possibly caused by low SERT, could well increase the risk of harm caused by this stimulant drug," said Dr. Kish.