It is hardly surprising that Tony Macie has an over-developed sense of awareness. As a US Army private he served for 15 months in Baghdad, calling in artillery and air support in his role as a member of a reconnaissance unit. Deadly roadside bombs and insurgent attacks were everyday occurrences in the city divided by sectarian violence. Being hyper-vigilant can help keep a soldier alive in a warzone, but when Macie returned home in 2007, he couldn’t switch off. “My brain was working on overdrive all the time,” he says. “I couldn’t relax, couldn’t unwind.”

He was diagnosed with Post-Traumatic Stress Disorder (PTSD), but found the standard treatments – mainly psychotherapy and anti-depressants – were of little help. While searching for an effective alternative, Macie came across the website of Multidisciplinary Association for Psychedelic Studies (MAPS). This not-for-profit group was sponsoring research into the use of MDMA, better known by its street name ecstasy, as a treatment for PTSD. He enrolled in a study that is currently looking at whether combined use of the drug and psychotherapy could provide relief for those with the debilitating anxiety disorder.

MDMA was originally developed by scientists at the German chemical and pharmaceutical company Merck a century ago, while they were investigating ways to stop abnormal bleeding. In the 1970s, a number of psychiatrists used the chemical to enhance communication with patients. The practice ended when MDMA became better known as a party drug, leading to it being outlawed in the US in 1985.

Evidence for its therapeutic efficacy was largely anecdotal. However, a small clinical trial published in 2010 suggested the drug can increase response to psychotherapy among people with PTSD. Now Rick Doblin, the founder and executive director of MAPS, hopes further studies, such as the one Macie is taking part in, will eventually lead to MDMA being approved by the US Food and Drug Administration as a new effective treatment option for PTSD. “Everywhere we go, what we’re told is ‘this is really important’, but the people we’ve spoken with were not high enough in the hierarchy to comfortably say yes,” says Doblin. He does, however, believe he is making headway. He recently had a meeting in the Pentagon to discuss his research (although he declined to identify the office on the record).

On trial

MAPS also funded the clinical trial published three years ago, which was led by Michael Mithoefer, a psychiatrist based in South Carolina. It involved 20 PTSD patients, the majority of whom had the disorder after being sexually assaulted, or being sexually or physically abused as children. Participants were given either MDMA or an inactive placebo during psychotherapy sessions, and were later assessed for symptoms of PTSD. Ten of the 12 (83%) given MDMA responded positively, compared to just two of the eight (25%) who took placebos.

Mithoefer’s interest in MDMA dates back to a career shift in 1991, when he moved from emergency medicine to psychiatry. “I was interested in experiential therapy, helping people shift their consciousness in some way,” he says. He became interested in MDMA's possible use in psychotherapy from anecdotal evidence reported prior to the drug's US ban. "There were published reports, but no controlled research," he says. PTSD was beginning to rise in the public consciousness in light of the wars in Iraq and Afghanistan. "I thought it behoved us to take a careful look at whether these anecdotal reports of MDMA could be born out with rigorous controlled trials."

Mithoefer is also running the trial that Macie is participating in. A group of 24 veterans and firefighters will take part in three sessions during which they will be given MDMA before undergoing psychotherapy. The hypothesis is that participants will feel less fear and be better able to talk about the traumatic experiences that caused their PTSD while under the influence of the drug.

One problem with the previous study was the use of inactive placebos. Those in the control group would have known that they were not receiving the active drug and this knowledge could have influenced their mental state. To get around this Mithoefer is giving those in the current study low, medium, or high doses. As participants will not know which does they have been given, he says this should effectively create double-blind conditions that would give the study greater validity. Results will be measured using a questionnaire-based PTSD diagnostic tool. The study is due to be completed next year.

Treatment options for PTSD are by and large ineffective, and so MDMA is not the only “non-traditional” treatment under investigation. At the Army’s Fort Bliss Restoration and Resilience Center in Texas, patients receive therapies ranging from acupuncture to Reiki, a Japanese spiritual treatment. In California, researchers at the Pentagon-funded Institute for Creative Technologies have studied the use of virtual reality as part of “exposure therapy” for veterans with PTSD.

Bad reputation

These days, researchers have no problems finding subjects for such work. It is estimated that the US military is diagnosing between 14,000 and 15,000 new cases of PTSD every year among deployed service members. “We have 400 veterans on a waiting list who have called us, and that’s without doing recruiting,” says Mithoefer.

Doblin thinks that getting MDMA through the FDA’s regulatory hurdles will only take eight to 10 years and $15 to $20 million – relatively speedy and cheap compared to what is normally required to license a new drug. “The FDA knows more about MDMA right now than any drug that they’ve ever approved in their entire history,” he says, pointing to a wealth of literature generated, ironically, by MDMA’s illegal status.

But whether the new research will convince critics, particularly those influenced by MDMA's reputation as a party drug, is more doubtful. Part of the problem is overcoming the stigma of hallucinogens, and some of the biased research that has been done in the past. Jonathan Moreno, a bioethicist and professor at the University of Pennsylvania, points to the studies conducted by Timothy Leary of Harvard in the 1960s. In a prison study, Leary claimed that hallucinogens combined with psychotherapy could reduce re-offending among prisoners, but those conclusions were later shown to be erroneous. Doblin published a follow-up study, highlighting problems with Leary's means of tracking re-offending in the long-term.

“It’s striking that even in the 60s and 70s people lined up on different sides on hallucinogens,” says Moreno. The lines are drawn pretty dark on various positions.”

It’s not just the recreational use and abuse of MDMA that raises concerns. There is what Doblin calls the “disastrous legacy of mind control experiments” at the Pentagon. During the Cold War, both the Army and the CIA experimented with using hallucinogens as a weapon. Particularly notorious was MK Ultra, a CIA project which experimented with the use of psychedelics for mind control, sometimes with unwitting subjects.

“That is in people’s minds,” says Doblin, adding that it has been sufficiently far in the past that it is not their dominant concern.” Doblin does say he was approached by a former member of the military who asked about the possibility of using MDMA, which fosters feeling of trust, as a tool for interrogating terrorists. “That was a scary thing,” says Doblin, who also expressed doubt such use would be effective.

The bigger barrier, Doblin says, is the fear of MDMA's recreational associations, and that it could be misused. Several researchers at the US Department of Veterans Affairs (VA) turned down requests to be interviewed about Mithoefer's MDMA study. "VA does not use ecstasy as a treatment for PTSD," said a spokesman in a statement. "Nor has it conducted, nor is currently conducting, any studies into whether it could be used in such a capacity." Ecstasy "is an illegal drug and VA would not involve veterans in the use of such substances."

For Macie, however, much of the debate is academic. He has taken part in one session of combined MDMA and psychotherapy as part of Mithoefer's study and already believes the approach has helped him. He does not see the drug as a magic bullet and recognises such treatment is likely to still require a great deal of effort on his part. “I don’t want you to think that doing it puts you in happy mode forever,” he says. “It’s hard work.”

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