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Look What They’ve Done to Their Brains

News from the Johns Hopkins Department of Psychiatry and Behavioral Sciences

The current word on ‘Ecstasy’ and its harm.

Dr. Una McCann
Dr. Una McCann

I want to see what I’ve done to my brain.”  Psychiatrist Una McCann doesn’t think twice now when people  enrolling in her studies say that, perhaps in a kidding way. She’s heard it before. But she’s well aware of the anxiety underlying the remark; it powers her work.

McCann and her neurologist husband, George Ricaurte, are world experts on the pathology of amphetamines. Much of their research has targeted MDMA, the chemical acronym for the drug most call Ecstasy. U.S. annual and lifetime use of the drug now matches that of cocaine. MDMA is as likely to be used by graduate students at all-night “raves” as by dropouts behind the 7-Eleven, and the former venue, studies suggest, may enhance its effects.

For more than two decades, McCann and Ricaurte have worked like mad to prove what studies with similar amphetamines have shown: that, in some users, MDMA causes immediate and likely long-term harm to the brain’s serotonin-releasing neurons. Now they’re near the point of settling the question once and for all. And as important, McCann, whose psychiatry training equips her to evaluate behavior, has been gathering evidence for what the neuro-damage leads t that MDMA also warps the brain’s activity in telling ways. 

In the 1980s, the first flurry of research worldwide confirmed that, in animals, MDMA leads to a steep drop in brain serotonin. Further, weeks after monkeys received it orally, the Hopkins team showed that the brain’s normal thatch of serotonin nerve axons and their endings had become a lacework of holes. In animals from rats to cats to monkeys, a dozen labs including theirs concluded that MDMA was bad news to neurons, even though the bodies of the cells didn’t die. And seven years after a dose—the longest interval tested—Ricaurte found squirrel monkeys’ brains hadn’t returned to normal.

“But the daunting task,” says McCann, has been to show that animal studies reflect what happens in people.” Some detractors—mostly a fringe of therapists convinced the drug is a shortcut to patient insight—say the animal studies don’t compare. Yet the Hopkins work suggests otherwise, and in looking at blood plasma levels of MDMA, the team may have an index that can apply to humans. Recently, they tied blood concentrations of the drug to brain damage in squirrel monkeys dosed in human-similar ways. Blood levels lowered brain serotonin reflected weeks later and matched those that other labs reported in people using Ecstasy. Plus, in both humans and animals, follow-up PET scans showed corresponding losses of nerve ending markers.

Do these people act different? “Effects might not be obvious if you’ve only taken MDMA a few times,” says McCann. The brain is good at compensating, she adds. But for heavier users she’s tested—and labs worldwide confirm—cognitive troubles, especially in short-term memory, crop up: “People can still carry on with their jobs, but they worry, for example, because they have trouble finding words.” And when she challenges volunteers’ brains with an agent that gives serotonin neurons a workout—much like treadmill tests for suspects of heart disease—they don’t respond normally. Sleep architecture, she adds, is also different: their ratio of slow wave to REM sleep changes. And a sophisticated technique called spectral analysis finds more subtle differences.

“It boils down to the fact that kids are taking a drug clearly toxic to any mammal you can think of,” McCann says, “and they think that’s OK.”

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Find other Hopkins Newsletter articles from past issues.