Pilot studies demonstrate effectiveness of MDMA for post-traumatic stress disorder
Ecstasy, a drug that is illegal in most countries, is showing increasing potential as a treatment for post-traumatic stress disorder (PTSD), according to clinical-trial results presented at a conference in San Jose, California, today. The effect seems to continue for years after the initial treatment.
People can develop PTSD after traumatic experiences such as sexual abuse, or witnessing extreme acts of violence. Patients are plagued by flashbacks and nightmares, and often become emotionally numb and easily frightened. Treatment includes cognitive behavioural therapy and selective serotonin reuptake inhibitors (SSRIs) such as paroxetine (Paxil) and sertraline (Zoloft), but many people with PTSD do not respond to these treatments.
Ecstasy, otherwise known as MDMA (3,4-Methylenedioxymethamphetamine), causes the release of neurotransmitters such as serotonin in the brain, and so could help to decrease the patient's fear and defensiveness during treatment The drug was used during therapy in the 1970s but with the rise of rave culture in the 1980s, the US Drug Enforcement Agency and the World Health Organization listed MDMA as a Schedule I drug — a classification reserved for drugs with no medical use and high potential for abuse — making it nearly impossible to use in clinical trials.
Since 1986, the Multidisciplinary Association for Psychedelic Studies (MAPS), a nonprofit research group based in Santa Cruz, California, has struggled to obtain permission to study the therapeutic potential of MDMA, other psychedelic drugs and marijuana, but now the group's efforts are beginning to bear fruit. The first two preliminary human trials, in the United States and in Switzerland, have had encouraging results, with most of the people with PTSD who were tested showing lasting improvements.
"The results were very promising, and there were no safety problems or serious adverse events, but we need to replicate this," says Michael Mithoefer, a psychiatrist based in Mount Pleasant, South Carolina, who led the US study.
The results were presented on Friday at the Psychedelic Science in the 21st Century conference, hosted by MAPS, which funded both pilot studies.
The US study was the first in the United States to look at the therapeutic effects of MDMA on PTSD, and was completed in late 2008. The 20 patients, mostly women, had been resistant to psychotherapy and standard PTSD drugs. Therapists administered MDMA to the patients during two or three 8-hour "experimental sessions", spread amongst a series of 20 to 30 psychotherapy sessions.
Two months after the last session ended, only 15% of the patients who received MDMA still met the criteria for PTSD, whereas 85% of the placebo group did.
In long-term follow-up, averaging 3.5 years after the initial treatment, most of the people remained free of PTSD — of the 16 patients who participated in the follow-up study, 13 still did not meet the criteria for PTSD. Mithoefer notes, however, that the people who have not yet elected to participate in the long term follow-up may have done so because they had not fared well.
"It's interesting, and sounds promising," says Kathleen Brady, a psychiatrist at the Medical University of South Carolina. But she notes that it's difficult to interpret the findings because the therapists were able to work out which patients received MDMA and which received placebo. "They could have been biased and treated the patients differently. That's definitely a concern."
In the second study, Peter Oehen, a psychiatrist in Biberest, Switzerland, followed the same protocol with 12 people with treatment-resistant PTSD. Although some people treated with MDMA showed an improvement in their symptoms, the results from this trial were not statistically significant.
"In a way the results were good enough to get approved as prescription medicine," says Rick Doblin, MAPS founder, pointing out that the SSRIs Zoloft and Paxil, which have FDA approval for treatment of PTSD have even more modest benefits for patients. "But it's true they were not as good as the US study. We're trying to understand why. It could very well be cultural variables, or therapist variables. We know it's not just the drug that does the work."
The difficulty with replicating the success of the US trial is not very surprising, says Murray Stein, a psychiatrist at the University of California, San Diego, who is director of a 10-site clinical consortium devoted to researching PTSD and traumatic brain injury.
"PTSD, and all of mental health research, is full of small, well-done studies that never get replicated," he says. "I'd love to see a bigger, well-powered study done. But until then, it's just kind of neat, but something I've seen 20 times before, something that often doesn't pan out."
MAPS has initiated a pilot study with US veterans and wants to run experiments in other countries, both to make sure the drug works in different cultural contexts, and to make the approval as a prescription medicine more likely. The group is now working to get approval for studies of MDMA for PTSD in four other countries: Canada, Israel, Jordan and Spain. But with these different governments and cultures come new hurdles.
"Things are much slower than we expected in Canada, where we'd be the first psychedelic research in 40 years," says Doblin. "And the biggest stretch is going to be in Jordan. That's a culture where the psychedelic experience of the 1960s didn't happen, so there's no reservoir of therapists and psychiatrists that know about these things from when they were younger."
That historical difference makes the Jordan study particularly important, says Doblin. "We want to show that these drugs can be mainstream," he says. "It's not just for people who have done drugs before. It's for normal people, for anyone."
April 16, 2010