AGONY AND ECSTASY

Ecstasy May Be Good for Those Who Can't Get Over Something Truly Horrible

"I'VE been shot in the leg. I've been beat up. But that's pretty
minor," says a 41-year-old American security contractor who spent
four years in Iraq. "But when you get a vehicle blown out from under
you and ambushed by six or eight al-Qaedas, it does tend to affect
one a little bit."

With a broken back, two broken feet and neurological damage, the man,
who asked that his name not be used, spent the next three months in
hospitals in Iraq, Germany and America. But though he was physically
on the mend by the start of this year, he found himself
incapacitated. "I was having nightmares right off the bat," he
recalls. "I couldn't do anything. Mostly, I'd just retreat to a room
and not leave."

Post Traumatic Stress Disorder, or PTSD, is the persistence of
debilitating psychological symptoms. It can include flashbacks and
nightmares, increased arousal in the form of insomnia, anger and an
inability to concentrate, and impaired personal relationships.
Although lasting psychological damage from horrific experiences has
been recognised since time immemorial, it is only since 1980, when
veterans were still experiencing stress from the Vietnam war, that
PTSD has been a formal psychiatric diagnosis.

By 2005 72,000 American veterans were receiving disability payments
for PTSD. A study two years later estimated that 12% of American
veterans from the wars in Iraq and Afghanistan suffer from PTSD. Thus
far, 1.8m Americans have been deployed in those two theatres,
implying 216,000 eventual cases.

Yet most PTSD sufferers are not drawn from the ranks of those for
whom trauma is an occupational hazard: 5% of American men suffer from
PTSD at some period in their lives. For American women, the rate is
double that, mostly from exposure to such crimes as domestic violence
and sexual abuse. Two in five rape victims are diagnosable with PTSD
six months after the attack. "It can go on for ever", says Kathleen
Brady, a professor of psychiatry at the Medical University of South
Carolina who studies the disorder, "but even after 30 years, PTSD is
treatable."

Treatment usually includes drugs and antidepressants such as Zoloft,
sometimes combined with psychotherapy. "There is a lot of evidence
supporting exposure-based therapy", says Dr Brady, "which means
re-living the events in a safe setting so patients can separate the
inappropriate effect from the trauma." Yet in at least a quarter of
cases chronic PTSD is resistant to all treatment.

Gail Westerfield, a writer who lives in South Carolina, was sexually
abused by a neighbour when she was a child, and later raped by an
acquaintance when a university student. She suffered a range of
symptoms including memory problems, bouts of depression, crying fits
and tremors.

She was diagnosed with PTSD a decade ago when she was in her 30s. But
she found this knowledge cold comfort. "I was probably on half a
dozen different kinds of antidepressants over the years", she says,
"and they never worked for me. I've had this my whole life, pretty much."

So the results of a clinical trial recently announced by Michael
Mithoefer, a psychiatrist in Charleston, South Carolina, are
encouraging. Twenty patients with PTSD who had resisted standard
treatments--including both Ms Westerfield and the security
contractor--were given an experimental drug in combination with
psychotherapy. After just two sessions all of them reported dramatic
improvement. The compound, methylenedioxymethamphetamine, or MDMA, is
not new. Known as Ecstasy, it is illegal nearly everywhere.

Dr Mithoefer's study is part of a broader resumption of research into
the therapeutic uses of psychoactive compounds. Scientists in North
America, Europe and Israel are studying the use of MDMA, LSD,
hallucinogenic mushrooms, marijuana and other banned psychoactive
substances in treating conditions such as anxiety, cluster headaches,
addiction and obsessive-compulsive disorder. They are supported by
private funds from a handful of organisations: the Beckley Foundation
in Britain; the Heffter Research Institute and the Multidisciplinary
Association for Psychedelic Studies (MAPS) in America.

This avenue of research--as opposed to research into the damage done
by recreational drug use--came to a halt in the 1970s when drug
prohibition became politically popular first in America and then in
the rest of the world. Though the "war on drugs" continues, the
approach is gradually becoming less dogmatic and more pragmatic. Even
so, research into therapeutic uses of banned drugs is fraught with
political considerations, often with bizarre results. For instance,
though medical marijuana is now recognised in many parts of the
world--in California more than 20,000 people are registered to use
it--there are few studies into its benefits.

Fun Has Its Uses

MDMA was first synthesised almost a century ago but was little
noticed until the 1960s when young American chemists began to ingest
it. Alexander Shulgin, a chemist at Dow Chemical in California who
had invented Zectran, the first biodegradable insecticide, had been
experimenting--in every sense--with mescaline and its chemical
relatives. Then one of his students suggested that he try MDMA. "By
golly", he recalls, "she was absolutely right: this was an
interesting compound."

Mr Shulgin left Dow to pursue psychoactive chemistry full-time. Over
a couple of decades he synthesised hundreds of chemicals, all of
which he tried first on himself and a small group of volunteers. One
of his collaborators was his wife, Ann. In the late 1970s the
Shulgins introduced MDMA to Leo Zeff, a Californian psychotherapist
who had developed LSD therapies in the 1960s when that drug was still
legal. Dr Zeff was so impressed that he postponed retirement and
became an enthusiastic proponent of the drug (which he called Adam),
introducing it to hundreds of other therapists in America and Europe.

But in the 1980s MDMA, which at the time was still unregulated,
escaped its semi-underground psychotherapeutic milieu and began to be
taken by young people for the sheer fun of it. In a panic, America's
Drug Enforcement Agency (DEA), unaware of the therapeutic MDMA
network, made an emergency classification in 1985 that placed MDMA in
Schedule I--the most restrictive category for drugs with "a high
potential for abuse" and "no currently accepted medical use".

Schedule I also includes marijuana, LSD, psilocybin, mescaline and
heroin (though rules vary widely: heroin, for example, is available
by prescription in Britain and some other countries). Cocaine,
amphetamines, opium, morphine and others are in Schedule II and can
be prescribed by doctors under DEA supervision. Although 500,000
doses of MDMA had by this point been used in therapeutic settings,
the compound was thereafter banned worldwide.

Some therapists went underground, continuing MDMA treatment
illegally, using illicit supplies. "It's a very simple compound to
make," remarks Mr Shulgin.

Ironically, once it became illegal, MDMA's recreational use exploded.
The UN estimates that at least 9m people--compared with 12m heroin
and 16m cocaine users--consume round about 100 tonnes of MDMA and
related compounds worldwide each year. The criminal nature of the
business makes it difficult to assess the dosage or purity of the
MDMA being consumed and it can have lethal effects. But millions of
people, rolling about on fake fur pillows or waving glowsticks to
electronic music, attest to feeling good. "The first time I ever did
it was literally the first time in my life that I felt good in my
body," says Ms Westerfield, who took MDMA recreationally in the 1980s
(half the study participants had swallowed the drug occasionally in the past).

In 1986 Rick Doblin, one of Dr Zeff's students, founded MAPS with the
goal of ushering MDMA through the formal drug-approval process of
America's Food and Drug Administration (FDA) and so bringing about
its rescheduling. Drug approval often takes big pharmaceutical firms
a dozen years at an average cost exceeding $1 billion. But Mr Doblin,
then a student, had time and enthusiasm on his side.

"Our whole approach is based on the idea that science matters at the
FDA," he says. No studies had been performed on the effects of banned
psychoactive drugs on humans since 1971 (though a thaw came in 1990
with a study to assess the relationship between schizophrenia and
dimethyltryptamine or DMT, a potent hallucinogen that occurs
naturally in the brain). Mr Doblin explains that since the FDA
insists that psychedelics should be treated like any other drug, "we
had to start with a Phase I safety study, where the drug is first
used on humans--even though millions of people had taken MDMA by
then." The study got going in 1992 at the University of California,
Los Angeles.

The results were positive but by the mid-1990s, when the study was
complete, MDMA had become even more controversial. It was not until
2000, when Mr Doblin met Dr Mithoefer, another of Dr Zeff's former
students, that the opportunity arose to propose a Phase II study on
the efficacy of MDMA in treating PTSD. Treatments began in 2004.

Dr Mithoefer's Phase II research, which used MDMA from the only legal
source--a chemist at Purdue University licensed by the DEA to
distribute controlled quantities from a supply synthesised in
1985--is directly descended from the first generation of LSD
psychotherapy. Subjects were given MDMA while attended by Dr
Mithoefer and his wife, a psychiatric nurse. They rested on a futon,
listened to music and were encouraged to revisit their trauma.

"I remember feeling incredibly safe and very motivated," says Ms
Westerfield of her first session. The security contractor from Iraq
concurs. "It helped me put the pieces of the puzzle together," he
says. "I was blown 15 feet through the air in a vehicle, and I forgot
the ride upwards. It made me remember it."

The patients who received MDMA showed statistically significant
improvement of their PTSD symptoms compared with those who received
the same day-long therapy sessions with an inactive placebo. "All the
major approaches involve revisiting the trauma in therapy", says Dr
Mithoefer, "but patients may be overwhelmed and retraumatised." He
believes the fear and defensiveness that characterise PTSD are
obstacles to treatment, and that it is MDMA's attenuation of these
emotions that permits concurrent psychotherapy to be effective. He
will publish the study shortly.

Several additional Phase II studies organised by MAPS are about to
start in Israel, Switzerland and Canada. A Phase III trial, in which
the methodology is extended to many more therapists and several
hundred patients, is still more than two years away. But eventually,
if two Phase III studies are successful, the next step would be
rescheduling MDMA. Dr Mithoefer is cautious, suggesting that looking
that far ahead is premature. "There's reason to think this may be an
exciting new treatment at some point," he says. "But it's a long way
to proving it in larger trials."

"We don't have failures", says Mr Doblin, "because we're working with
drugs that have been tested in the underground, and work." Government
research into the harmful effects of these drugs has, curiously,
helped his cause: "There are over 3,000 papers on MDMA that have cost
more than $200m to produce," he says. He estimates that, thanks to
these bodies of formal and informal knowledge, MAPS can take MDMA
through the approval process for only about $10m.

While the bureaucracy rolls on, a few people are watching the results
with personal interest--and impatience. "There are other things that
I would still like to work on," says Ms Westerfield, whose last
MDMA-assisted therapeutic session was four years ago. "That's why I
hope it gets approved sooner rather than later."