THE HIGHS AND LOWS OF ECSTASY

TIMES HEALTH WRITER

Sue Stevens was severely depressed after her young husband, Shane, succumbed to kidney cancer in 1999. She took large doses of numbing antidepressants to get through the day, and conventional therapy didn't help.

Then, last fall, the 32-year-old Chicago woman chose a more radical approach. She traveled to the West to see a psychologist whom she had learned was using the illegal drug Ecstasy for a handful of patients suffering from severe trauma. In a single session, under the influence of Ecstasy--a drug that combines the effects of a psychedelic and an amphetamine--she said she was finally able to come to grips with her grief.

"Somehow, I knew Shane was no longer hurting, which made it possible for me to let go," said Stevens, who hasn't taken any antidepressants since. "It was like a wire that was disconnected got reattached and jump-started the healing process. Even if this feeling was just an effect of the drug, it's what I needed to do to move forward."

Anecdotal reports from other mental health professionals suggest similar results from Ecstasy, said Rick Doblin, president of the Multidisciplinary Assn. for Psychedelic Studies, a nonprofit group in Boston that funds psychedelic research. "There's a whole network of 30 to 40 people around the country--some are psychiatrists, some are psychologists--who risk their licenses to use MDMA [the chemical name for Ecstasy] with their patients," he said.

Lester Grinspoon, a professor emeritus of psychiatry at Harvard Medical School who has studied psychedelics but is not among the therapists prescribing Ecstasy to patients, said the synthetic drug can "greatly accelerate" the therapeutic process. "It enhances one's capacity for insight and empathy, and melts away the layers of defensiveness and anxiety that impedes treatment," he said. "In one session, people can get past hang-ups that take six months of therapy to untangle."

Other doctors, however, contend that MDMA is too dangerous to justify its use for any therapeutic purpose. "There's no scientific evidence that MDMA is beneficial; it's all anecdotal," said Dr. George Ricaurte, an associate professor of neurology at the Johns Hopkins School of Medicine in Baltimore. Giving patients even one dose of Ecstasy, he believes, is unethical because of its potential to harm.

The intense but largely unknown scientific debate over MDMA's possible pyschotherapeutic use has been overshadowed by the recent storm of publicity about the health risks of the drug. The news is filled with horror stories of kids overdosing on Ecstasy at all-night parties, of machine-gun shootouts over Ecstasy deals gone bad and of disturbing surveys that show it is the fastest-growing illegal drug in America.

Fueling concern over Ecstasy's safety has been a growing number of studies that suggest it may alter the brain, impair memory and concentration, dull one's intelligence, and cause chronic depression and anxiety. That has led Alan Leshner, director of the National Institute of Drug Abuse, to distribute thousands of postcards with images of brain scans labeled "Plain Brain/Brain After Ecstasy." Yet some credible researchers insist that Ecstasy may be a valuable therapeutic tool when used with professional oversight. They contend that critics have exaggerated the drug's dangers, using weak science to bolster their arguments.

"The issue has become so politicized that it's impossible to get a fair, objective hearing," said Dr. Charles S. Grob, director of Child and Adolescent Psychiatry at Harbor-UCLA Medical Center in Torrance. Grob helped conduct government-sanctioned tests of MDMA on humans in 1995.

There is one thing, though, on which both supporters and critics of Ecstasy can agree: The recreational use of the drug is dangerous. Some people take multiple doses of Ecstasy, and the drug is often adulterated with other substances to create a potentially toxic mixture. And Ecstasy is often taken with other illegal drugs in crowded, overheated dance clubs, where users can become severely dehydrated.

Some mental health professionals say that rampant street use of the drug has tainted the reputation of a potentially valuable tool for treating mental ills that are resistant to conventional therapy, including alcoholism, drug addiction and post-traumatic stress disorder.

In addition, studying the parts of the brain stimulated by mind-altering compounds like MDMA gives scientists insights into brain chemistry. This understanding can assist them in formulating more effective medications for mental ills.

The scientific community has long had an ambivalent attitude toward compounds like MDMA: tantalized by what they can teach us about brain circuitry and their therapeutic promise, but fearful of their possible adverse effects.

The history of LSD is a case in point. Lysergic acid diethylamide was devised in 1943 by Swiss chemist Albert Hofmann. Apparently, some LSD seeped through his skin while Hofmann was working with the chemical in his lab. While bicycling home, the scientist experienced the first documented "acid trip."

LSD's discovery fueled a flurry of research by scientists attempting to identify the brain regions stimulated by the drug. LSD also ignited interest in serotonin, a chemical messenger in the brain that we now know regulates mood, sleep, libido, impulses and body temperature.

When serotonin was first isolated from blood cells in 1947, scientists thought it just constricted blood vessels. Then researchers noticed that serotonin and LSD had common chemical structures, which suggested the two compounds had a similar effect on the brain. Suddenly, serotonin became the subject of intense scientific scrutiny because it was believed to play a role in mental illness and schizophrenia.

This research paved the way for the development of antidepressants such as Prozac, Zoloft and the class of antidepressants known as SSRIs, or selective serotonin reuptake inhibitors, which maintain high levels of serotonin the brain.

"If LSD hadn't been discovered, it may have taken decades, not years, before we figured out what serotonin did," said David E. Nichols, a professor of medicinal chemistry and pharmacology at Purdue University in West Lafayette, Ind.

LSD Effective for Some Addictions

LSD also proved effective in treating alcoholism and heroin addiction in studies conducted in the 1960s in Canada and Europe, chalking up recovery rates in the 40% to 50% range--much higher than traditional treatments. But research abruptly ceased in the United States in 1966 when the federal government banned LSD.

Despite scientists' efforts to maintain secrecy, MDMA met a similar fate. First synthesized in 1912 by German chemists at Merck Pharmaceuticals, the compound is both a stimulant like cocaine, which means it can raise a person's body temperature, blood pressure and heart rate, and a hallucinogen. In 1976, after publication of the first scientific paper on MDMA's psychoactive effects on humans, psychotherapists quietly began experimenting with it. One estimate suggests that perhaps 500,000 doses of MDMA were dispensed by therapists during the late 1970s and early 1980s, said Doblin, of the Boston psychedelic research group. MDMA was hailed by these therapists as a "penicillin for the soul."

"It augmented therapy by enhancing communication and intimacy, and allowed people to access repressed feelings and memories in a nonthreatening atmosphere," said Grinspoon, who has taken MDMA and said it led him to "extraordinary" personal insights.

Psychiatrist George Greer, for instance, conducted more than 100 therapeutic sessions with MDMA in San Francisco and Sante Fe, N.M. According to Greer, use of MDMA helped ease the pain of a cancer patient and assisted the daughter of a Holocaust survivor to rid herself of "the concentration camp consciousness that had colored her entire life." Greer also used the drug in couples therapy. "Virtually every couple said their intimacy and communication was greatly improved," he recalled. "They were able to bring all the skeletons out of the closet without being afraid their partner would reject them or feel betrayed."

MDMA's development as a therapeutic aid was derailed in the early 1980s by one enterprising patient, who recognized its lucrative potential as a party drug. He renamed it Ecstasy, and the so-called "love drug" became popular on the college party scene. In 1985, the Drug Enforcement Administration banned the use, possession and manufacture of MDMA, and therapeutic research in the U.S. came to a halt.

Soon, reports about MDMA's dark side surfaced. University of Chicago researchers reported that people taking MDMA were sensitive to even minor changes in ambient room temperature and could easily get overheated, possibly resulting in severe dehydration and even death. Other experiments in laboratory animals indicated even one dose of the drug damaged the ends of serotonin neurons, though scientists still aren't sure if that's necessarily detrimental.

In studies involving primates, exposure to MDMA caused brain damage that was evident six to seven years later. In humans, the toll from chronic use seems even more disturbing. Tests done at Johns Hopkins University in Baltimore revealed that frequent MDMA users had subtle deficits in memory and concentration. Other studies suggested that habitual Ecstasy users didn't do as well on standard intelligence tests.

"The evidence is extremely compelling that MDMA is harmful," said Johns Hopkins' Ricaurte, who conducted many of these studies.

Other scientists, however, think the jury is still out. Part of the problem is that most experiments showing MDMA's deleterious effects have been done on habitual users who mix it with other illegal drugs. Or the research subjects have taken Ecstasy laced with other drugs. So identifying the actual source of the trouble can be tricky.

An autopsy of a 26-year-old chronic Ecstasy user who died of a drug overdose is a good example. His family donated his brain to scientific research in hopes of learning about how Ecstasy alters the brain. Scans of slices of his brain revealed that serotonin levels were reduced by 50% to 75% of normal levels. Critics have used this information to argue that Ecstasy leaves the brain practically moth-eaten--a fact that is not yet supported by research.

Scientists do know that Ecstasy triggers the release of massive amounts of serotonin from its storage sites, which is why users experience a feeling of euphoria. Artificially flushing the brain with so much serotonin eventually depletes reserves of this crucial brain chemical. Consequently, after weekend drug binges, people often experience a profound emotional letdown--a condition known in the Ecstasy-drenched Rave scene as "the terrible Tuesdays."

However, the individual whose brain was autopsied used many other drugs and may have had an underlying psychiatric disorder, said Stephen Kish, a University of Toronto pharmacologist who conducted the autopsy.

Kish speculated that the severe serotonin depletion might have been a symptom of depression. Or it might have been due to the cumulative effects of the combination of drugs that he habitually ingested. Or perhaps it was simply a reaction to taking six to eight times the normal dose of Ecstasy, as he had done just before he died.

"There was an extraordinary amount of Ecstasy in his bloodstream so we really don't know whether the damage was permanent or reversible," said Kish. "Still, the available evidence is pointing in the same direction. The question is: Do you want to play Russian roulette with your future?"

Swiss researchers, however, found that there was no apparent brain damage in people who used chemically pure Ecstasy only a few times. In a study done last year of people who had never taken the drug, 10 subjects were given a single dose of MDMA while an equal number received a placebo.

A month later, researchers used a PET scan to take snapshots of participants' brain activity. The images revealed there were no changes in the serotonin neurons.

"It was a small sample, so I can't say with total certainty that MDMA isn't harmful," said Dr. Franc X. Vollenweider, a psychiatrist at the Psychiatric University Hospital of Zurich who led this study. "But what I can say is that if you use it a few times in a clinical setting, it won't do brain damage."

There also may be some hard data soon on MDMA's ability to enhance conventional psychotherapy. Two studies are exploring whether Ecstasy can help people recover from traumatic events, such as rape, incest or physical abuse.

Scientists in Madrid have begun prescribing MDMA for rape victims who haven't responded to conventional counseling. Researchers believe the drug will reduce these patients' intense fears so they won't feel emotionally threatened in therapy sessions.

In South Carolina, scientists are seeking government approval to test the drug's effects on victims of rape and other assaults and who have been diagnosed with post-traumatic stress disorder. They believe MDMA may help to overcome the key stumbling blocks in treating these victims.

"People who have been abused have trouble trusting others, which is a real impediment to establishing a therapeutic relationship, and reliving traumatic incidents can provoke incredible anxiety," said Dr. Michael C. Mithoefer, a clinical assistant professor at the Medical University of South Carolina in Charleston. "We believe that using MDMA will make it possible for them to work through their trauma without feeling their fears, and to trust their therapists."

Still, experts sound a cautionary note. "I'm not saying this type of research shouldn't be done," said Johns Hopkins' Ricaurte. "But this is a drug that has documented potential for abuse. So human experiments must be done in the most careful and clear-minded of circumstances."

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