Somewhere in Charleston, S.C., in a safe bolted to the floor and protected by an alarm system, Michael Mithoefer keeps his supply of Ecstasy.

He is not a dealer or a user; he is simply following federal Drug Enforcement Administration rules. The DEA ordered him to keep it secured in a secret place.

"You could probably go down to the local college campus and buy a lot more with a lot less trouble than breaking into the safe," he jokes.

Mithoefer, a psychiatrist, is one of a handful of people in the country allowed to do human research with Ecstasy, which the government puts in the same legal category as heroin. He is studying whether Ecstasy can help trauma victims heal their emotional wounds. The research has put him at the center of an intense debate over the drug's potential as a legitimate medical treatment.

A small group of determined supporters - among them researchers and doctors at Harvard University and the University of California at Los Angeles - have spent more than a decade fighting with the government and institutions for permission to do research. A few months ago, after years of wrangling, the DEA finally signed off. Mithoefer's study is the first U.S. trial of Ecstasy's therapeutic value.

Advocates say the drug could help treat a range of psychological problems. "I'd like to see it widely used in psychiatry," said Harvard psychiatrist John Halpern, a leading proponent. "It is potentially a very valuable tool."

But some scientists and officials question the research, saying the drug has been proved to cause permanent harm to the brain, particularly to memory. "Let's not kid ourselves. The bulk of the evidence is on the side of risk," said David Murray, a policy analyst at the White House Office of National Drug Control Policy. "The only question is how permanent and how extensive the damage is."

The controversy echoes the long-running dispute between advocates and the federal government over the use of marijuana for a range of ailments, including glaucoma and nausea.

Although it has been illegal in the United States since 1985, Ecstasy, - popularly called "X" or "E" - is widely used as a recreational drug. More than 3 million Americans take the drug at least once a year, according a 2002 government survey. Unlike heroin and cocaine, Ecstasy is not physically addictive. It has stimulant and hallucinogenic properties, and it generally gives users a sense of euphoria and contentment without impairing cognitive or motor abilities, as alcohol does.

Ecstasy pills are produced in illegal laboratories in the United States and abroad.

Mithoefer's source of the drug, whose chemical name is 3,4-Methylenedioxymethamphe- tamine, or MDMA, is a government-licensed lab.

'Trapped in the past'

Mithoefer, Halpern and others think the drug could be particularly helpful for people with post-traumatic stress disorder (PTSD). Many patients can't bring themselves to talk about the painful events that triggered their problems. Ecstasy, the theory goes, could help people confront these traumas.

"MDMA makes people comfortable with themselves. It brings them into the moment," said Rick Doblin, director of the Multidisciplinary Association for Psychedelic Studies, a nonprofit group funding Mithoefer's research. "With PTSD, people are trapped in the past."

Although Doblin, 50, is not a doctor or a researcher, he has extensive experience with the drug, having taken it more than 100 times. "It's contributed enormously to my life," he said. Over the past 20 years, he has devoted himself to spreading the idea that Ecstasy and other hallucinogens have important medical benefits.

The South Carolina trial, which will cost $250,000, represents a milestone in his quest. If it goes well, Doblin hopes to fund larger national studies. His ultimate goal: persuading the Food and Drug Administration to approve MDMA as a prescription drug.

Mithoefer's study involves 20 subjects: 12 will take the drug, and eight will receive a placebo. Patients will take it twice during a 12-week course of psychotherapy. After taking Ecstasy, patients spend eight hours talking to Mithoefer and another therapist, trying to work through especially difficult problems. Early results are promising, Mithoefer said, but the study won't be complete until next summer.

'Incredibly frustrating'

MDMA therapy is not new. Before the drug was criminalized, a few hundred psychiatrists and therapists around the country were using it. Although no controlled studies were done, many who tried the method say it worked.

Between 1980 and 1985, George Greer used the technique with about 200 patients. The psychiatrist in Santa Fe, N.M., said almost all thought the therapy helped them. He finds it "incredibly frustrating" that he can't use the drug in his practice. "I see patients every day who could benefit," he said.

Proponents of the therapy take pains to distinguish it from recreational use, which they see as potentially dangerous. Street users aren't in a controlled setting, they say, and often unknowingly take pills tainted with methamphetamine and other drugs.

During the MDMA sessions in Mithoefer's trial, an emergency room doctor and a nurse are in the next room. The drug often raises body temperature and in rare cases causes fatal hyperthermia.

'Neurotoxicity'

What concerns some researchers more than overheating is the possibility that even a few doses of MDMA could cause permanent brain damage. Over the past decade, the question of Ecstasy's "neurotoxicity" has engendered enormous controversy. Some animal research has found that even small amounts of the drug harmed brain neurons that release serotonin, a key neurotransmitter involved in memory. In some studies, memory deficiencies persisted long after the drug was taken. And some human research on Ecstasy users has also found memory problems.

"There's a consensus that MDMA has the ability to damage brain serotonin cells," said Johns Hopkins University neurologist George Ricaurte, a leading MDMA researcher.

Last year, Ricaurte was forced to retract several studies that found grave neurotoxic effects in primates. Researchers had accidentally used methamphetamine rather than MDMA. But Ricaurte and others say the discredited findings don't change the overall picture - most scientists still think Ecstasy can injure the brain.

Some also worry that Mithoefer's study could confuse potential users about the drug's risks. The research sends a message that MDMA "is not only safe, but it's therapeutic," said Glen Hanson, a neuropharmacologist at the National Institute on Drug Abuse, a government research agency. Although not opposed to the current trial, Hanson suspects that the risks of MDMA therapy will outweigh the benefits.

Proponents of the approach agree that those who take the drug many times may risk brain damage. But they say therapeutic doses - one or two over a few weeks - are far below potentially harmful levels.

"The neurotoxicity issue has been hyped," said Charles Grob, a UCLA psychiatry professor. "The notion that one or two doses will induce irrevocable harm - that's wrong." Grob and Halpern, the Harvard researcher, have studied the drug's safety and found that low doses caused no permanent changes to brain structure or memory function in humans.

Advocates argue that even if higher amounts do cause damage, that is no reason to ban all use of MDMA. "Most of the drugs we use in medicine can be dangerous or even lethal if you take too much," Mithoefer said.

Ricaurte agrees, and said Ecstasy may well end up being seen as both a dangerous drug of abuse and a helpful treatment.

"Look at morphine," he said. "It has potential for abuse, but it's also a great painkiller. MDMA is no different."

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