Publishedin the Economist: http://www.economist.com/science/displaystory.cfm?story_id=12792611
Dec 18th 2008
From The Economist print edition
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 was blown 15 feet through the air, and forgot the ride upwards”
“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.”