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What a Long Strange Trip It's BeenEcstasy, the new prescription drug?

By Amanda SchafferPosted Tuesday, Jan. 23, 2007, at 12:52 PM ET

EcstasyThis year, the drug MDMA, otherwise known as ecstasy, could take a step toward medical respectability. Researchers in South Carolina have begun experimenting with MDMA for patients with post-traumatic stress disorder. At Harvard, a long-awaited pilot study will begin on whether the drug can help relieve anxiety and pain in terminal cancer patients in connection with psychotherapy. And studies will also start in Switzerland and Israel, where a former chief psychiatrist of the Israel Defense Forces will oversee work with people whose PTSD stems from terrorism or war.

Ecstasy gained notoriety as a party drug in the 1980s and 1990s. (Recall teenagers at raves with sparkly eyes and pacifiers rolling and dancing all night; a revival appears to be under way in England.) Enthusiasts say the drug makes them feel relaxed, energetic, and mentally clear. One likened it to a six-hour orgasm. In rare cases, however, users died after dancing for hours and overheating, or after taking mixtures of ecstasy and other drugs. Animal studies have shown that long-term, heavy ecstasy use can be risky for the brain. Human studies have found some ill effects in chronic users, as well. The government classifies MDMA (or 3,4-methylenedioxymethamphetamine) along with heroin, LSD, and marijuana as a Schedule 1 drug, which means that it's illegal and has no recognized medical uses.

But research has not proved that moderate or low doses of ecstasy are particularly dangerous. And avant-garde psychiatrists have long argued that in a controlled clinical setting, low amounts can play a role by reducing fear, without sedation, and so encourage openness and emotional insight. "There is nothing else like this in psychiatry—a fast-acting anti-anxiety medication that makes people alert and talkative," says Julie Holland, a psychiatrist at NYU Medical Center. If available to treat patients, "It would be incredibly useful." Some mental-health professionals interested in exploring MDMA's therapeutic uses protested when the government made it illegal 20 years ago. Stories of the drug's power to combat the psychological effects of terminal illness have continued to surface over the years. But proponents have had little but anecdote to go on. The current wave of studies should bring new rigor to answering an old question: whether MDMA deserves to be a prescription drug.

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MDMA was patented more than 90 years ago by the German chemical company E. Merck. For years, it was essentially shelved for reasons that aren't clear. In the 1950s, the U.S. Army conducted research on MDMA, perhaps as a potential incapacitant or truth serum, but apparently dropped the idea. The compound was rediscovered in the late 1970s by chemist and psychedelic cult hero Alexander Shulgin, who synthesized it for recreational use (and supplied it to at least one psychiatrist interested in trying it with patients).

Ecstasy works by prompting the brain to release a flood of neurotransmitters, including serotonin, which is believed to kick off the sensations of physical pleasure and euphoria. That sounds nice, but animal research suggests that high doses of the drug can cause the nerve endings that release serotonin to degenerate, ultimately lowering its levels in the brain. Some studies suggest that heavy users sustain damage to their serotonin systems. Long-term users may also experience increased anxiety, depression, or sleep disturbances. Recently, researchers in the Netherlands reported preliminary findings to suggest that in new users, low doses of ecstasy can alter blood-flow patterns in the brain and may result in small decreases in verbal memory.

In truth, this litany of harms is not as scary or as conclusive as it sounds, however. The best-known neuroimaging work purporting to show ecstasy-related long-term damage to the human serotonin system was fraught with methodological problems. Much of the research on the drug's apparent psychological or behavioral effects in chronic users fails to account for other drugs, like cocaine or marijuana, which ravers often take, as well. Nor does most research account for other substances like methamphetamine, DXM, and ketamine that pills sold as X may contain.

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Amanda Schaffer is a science and medical columnist for Slate.
Photograph courtesy of the Drug Enforcement Administration.
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