THE HIGHS AND LOWS OF ECSTASY

First it was an intriguing experiment in therapy, then a nightclub scourge.
But some experts say its healing potential should not be ignored.

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 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 commonly 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, or
dummy pill. 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."