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E-fer Madness Larry Smith Salon.com September 16, 2003 See also X'ed Out (Part 1) and Monkey Gone to Heaven (Part 2), also by Larry Smith and published in Salon on July 30 and July 31, 2003 Sept. 16, 2003 In a bizarre turn of events, the results of the most widely publicized study on the effects of Ecstasy on the brain were recently retracted. Published in the journal Science in September 2002, the study found that Ecstasy dramatically damaged monkey brain cells and was even deadly in some instances. At the time the study was released, former National Institute for Drug Abuse (NIDA) director Alan Leshner called taking Ecstasy "playing Russian roulette with your brain." But critics scratched their heads, wondering how 40 percent of the test animals could die when so few humans actually OD on MDMA. Almost a year later, an investigation conducted by the study's own researchers has revealed that the monkeys were given speed, not the popular club drug. The lab animals, it seemed, were misdosed. Although MDMA was invented in 1912 by the pharmaceutical company Merck, its value -- and its dangers -- began to be intensely debated only in the late '80s. From gray-haired professors to teen members of the harm-reduction organization DanceSafe, the pro-MDMA movement argues that when used safely, MDMA can be a miracle medicine for empathy and psychotherapeutic breakthroughs. Yet as it emerged from underground therapy circles and the London rave scene in the early '80s, it was subject to widespread use and abuse. In 1985, it was declared a Schedule 1 narcotic, a class of drugs deemed to have a high potential for abuse and no sanctioned medical use. Since that classification, Ecstasy use in America has increased each year. In 2000, the Drug Enforcement Administration seized 949,257 tablets, up from 13,342 in 1996. In a two-part series this summer in Salon that brought on its own debate, I investigated the drug's appeal and downsides. My exploration was spurred by the now delegitimized report that appeared in the Sept. 27, 2002, issue of Science, the weekly peer-reviewed journal of the American Association for the Advancement of Science. One of the world's most esteemed research journals, Science published the results of a study called "Severe Dopaminergic Neurotoxicity in Primates After a Common Recreational Dose Regimen of MDMA ('Ecstasy')," aka the monkey study. Johns Hopkins neurologist Dr. George Ricaurte (working with three other researchers including Dr. Una McCann), aiming to mimic human Ecstasy habits, injected five monkeys with high doses of what he thought was MDMA every three hours. Some monkeys died; others experienced damage to the cells that secrete the brain chemical dopamine, damage that can cause symptoms similar to Parkinson's disease. From NPR to the New Scientist the news spread, and the news was bad: Even one hit of the "club drug" can fry your brain, cause Parkinson's, or even kill you. Frightening facts for millions of Ecstasy users across the globe, but the reports were based on false data. The researchers had made a major error: They accidentally gave the monkeys methamphetamine -- aka speed -- not methylenedioxymethamphetamine (MDMA), commonly called Ecstasy. Speed is widely known to affect the brain's dopamine system, which in turn affects thinking and movement -- so Parkinson's-like symptoms would be expected. How does one of the nation's most prestigious and well-funded research labs make such a colossal blunder? And how can such an error go undetected (or unacknowledged) for almost a year? As detailed in the current issue of Science, where the study is officially retracted, Ricaurte explains that the labels provided by the lab's longtime supplier, Research Triangle Institute, were incorrect. Methamphetamine would be expected to produce the brain damage seen in the monkeys, the researchers said in their retraction. (If you've ever met a speed freak, that comes as no surprise.) When the researchers couldn't reproduce the data in subsequent studies (though this time they gave the animals oral doses, rather than injections as they had in the first study), they retraced their steps, finally realizing their mistake: A bottle of meth and a bottle of MDMA arrived in the same package and were evidently mislabeled. "This is the kind of retraction nobody likes, but the only villain -- if there is one -- is the vendor that sent the compounds in mislabeled vials," says Donald Kennedy, editor of Science. "It is not unusual for experienced investigators to trust vendors they have worked with, and these authors had no reason to mistrust the labeling." Research Triangle Institute did not return phone calls by press time. Neither Ricaurte nor McCann responded to repeated phone calls and e-mails from Salon. On Sept. 6, Ricaurte did tell the New York Times: "The laboratory made a simple, human error. We're scientists, not politicians. We're not chemists. We get hundreds of chemicals here. It's not customary to check them." According to the Baltimore Sun, Ricaurte's team is in the process of retracting another study -- which used the mislabeled vials -- linking MDMA to brain damage. Johns Hopkins, which says it has no plans to take disciplinary action against the research team, released the following statement: "While it is unfortunate the labeling error occurred, this in no way undermines the results of numerous previous studies performed in multiple laboratories worldwide demonstrating the serotonin neurotoxic potential of recreational doses of MDMA in various animal species, including several primate species. The study results replicate what was previously published regarding the neurotoxic effects of methamphetamine use, and the researchers' efforts to investigate conflicting data in the laboratory are an excellent example of how science is self-correcting." While it appears that a simple human mistake occurred, it's reasonable to ask why the study was published and so widely publicized without undergoing more fail-safe measures, which presumably would have exposed the egregious error. "The paper was peer-reviewed carefully by experienced, capable referees," says Science's Donald Kennedy. "The results and the presentation wouldn't have suggested that there was a problem, so I can't fault that process. And the authors did a hard thing: They discovered the problem and came right to us with the retraction." While retractions in peer-reviewed journals such as Science are extremely rare and indeed newsworthy, the initial bad data takes on a life of its own. "One thing about retracted articles, they can be officially retracted, but the original article never goes away," says Michael Castleman, who has written on medicine and health for the past two decades. "The original study gets out on Medline [the medical research Web site] and other research hubs and will be quoted for 10 years. News of the study runs on Page 1, the correction runs on Page 17."
See also X'ed Out (Part 1) and Monkey Gone to Heaven (Part 2), also by Larry Smith and published in Salon on July 30 and July 31, 2003
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