Published online 13 November 2008 | Nature | doi:10.1038/news.2008.1229

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MDMA may boost the benefits of psychotherapy, trial suggests.

The controversial drug MDMA - known to recreational users as 'ecstasy' - can help ease the effects of post-traumatic stress disorder (PTSD), according to the first phase-II clinical trial into the potential therapeutic benefits of using the drug as an adjunct to psychotherapy.

Most patients in the trial who were given psychotherapy treatment along with doses of MDMA (3, 4-methylenedioxy-<i>N</i>-methyl amphetamine) experienced statistically significant reductions in the severity of their condition after two months, compared with a control group who received psychotherapy and a placebo.

MDMA may help those undergoing psychotherapy to be less defensive and trust their therapist more, helping their recovery. Punchstock

"It's important to realize this is a small pilot study and it will be necessary to replicate the results elsewhere," says Michael Mithoefer, a private-practice psychiatrist based in South Carolina who led the study. "But it's evidence that this should be studied further."

Mithoefer believes that MDMA tends to decrease levels of fear and defensiveness and increase levels of trust when used in a clinical setting. "It can remove some of the obstacles in therapy and act as a catalyst to the therapeutic process," he says.

"As someone who sees people with severe untreatable PTSD in my clinic, I think these results are very exciting," says David Nutt, a psychopharmacologist at the University of Bristol, UK. "These data give further credence to the idea that there's a medical use for MDMA."

The results, which have yet to be submitted to a peer-reviewed scientific journal, were presented today at the 24th annual convention of the International Society for Traumatic Stress Studies in Chicago, Illinois.

Powerful flashbacks

MDMA is an illegal drug of abuse in Europe, the United States, and many other countries, but its therapeutic promise for trauma victims was first investigated by psychotherapists in California in the 1970s and early 1980s when the drug was relatively unknown, and still legal (see 'A Brief History of MDMA')1.

The symptoms of PTSD usually strike within three months of a person being involved in a disturbing event, such as sexual assault, torture, warfare, or witnessing a severe accident. The condition can lead sufferers to become withdrawn, depressed and unable to function because of powerful flashbacks that repeatedly expose the victim to the debilitating emotions of the original event. A combination of cognitive behavioural therapy and treatment with drugs such as Seroxat (paroxetine) can lead to recovery within months. However, Nutt points out that up to 20% of patients do not respond to any conventional treatments.

Mithoefer spent more than five years seeking approval to find out whether MDMA can help those non-responsive patients. His study was funded to the tune of $1 million by the Multidisciplinary Association for Psychedelic Studies (MAPS), a psychedelics advocacy group based in California.

Traumatic times

Most of the 23 treatment-resistant patients in the study were female victims of sexual trauma; two patients were male veterans of the 2003 Iraq war. The patients completed a series of tests to assess the severity of their PTSD, before undergoing a series of therapy sessions - one of which was conducted after taking either MDMA or a placebo. Four days later they underwent further psychological tests and therapy sessions.

After this whole sequence had been completed twice, subjects who received the placebo could then opt to move onto an open-label trial so that everyone could experience treatment having taken MDMA. A total of 21 participants completed all three rounds of the full experimental cycle.

Two months after the last experimental session, psychologist Mark Wagner of the Medical University of South Carolina, who was not involved in any of the experimental sessions, assessed the patients' PTSD symptoms. Ninety-two per cent of participants had a clinically significant reduction in their clinician-administered PTSD scale (CAPS) scores of 30% or more. Only 25% of the placebo group saw comparable reductions in CAPS scores. No ill-effects were seen in any of the participants.

Mithoefer believes that it is the combination of therapy and MDMA that is effective, and not the drug alone. "Subjects need good follow-up to help integrate the experience because it can stir up strong emotions," he says.

Small hope

Whereas Nutt agrees with Mithoefer that the results should prompt follow-up studies, Simon Wessely, a psychiatrist based at King's College London, UK, says the study is far too small to draw any meaningful conclusions. "In my experience, treatment-resistant PTSD is a complex disorder with many causes – we should be very cautious about any 'miracle' cures," he says. As consultant adviser in psychiatry to the British Army, Wessely adds that he will not be recommending this treatment based on current evidence.

Swiss psychiatrists have previously reported data on MDMA use in a therapeutic context, but the subjects also received LSD psychotherapy. Although the results were broadly positive, it was not possible to separate the effects of each drug. A similar MDMA-PTSD trial in Spain, which ran between 2000 and 2002, was halted following negative publicity after several local deaths associated with recreational use2. Other MDMA-PTSD studies are underway in Israel and Switzerland.

MAPS founder, Rick Doblin, is in no doubt that the results are of fundamental significance. "For the entire 22 years of MAPS' existence we've been struggling to study the therapeutic use of MDMA," he says. "And the results suggest MDMA psychotherapy can be more effective than any prescription medicine currently available from the pharmaceutical industry."