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 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."