Ecstasy for PTSD: Not Ready for Prime Time

Hundreds of desperate combat veterans with Post-Traumatic Stress Disorder (PTSD) are reportedly seeking experimental treatment with an illegal drug from a husband-wife team in South Carolina. The Bonhoefers recently published a study showing that adding MDMA (ecstasy, the party drug) to psychotherapy was effective in eliminating or greatly reducing the symptoms of refractory PTSD. It was widely covered in the media, for instance in this article in the NY Times. It was only a small preliminary study, and the treatment is not yet ready for prime time; but media reports have sparked enthusiasm not justified by the evidence.

The Study

The study is available online. To summarize the highlights:

  • Subjects were 20 patients with chronic PTSD refractory to both psychotherapy and psychopharmacology.  85% were women, mostly victims of sexual assault or childhood abuse, and there was only 1 subject with combat stress.
  • Randomized.
  • Placebo controlled: 12 patients got the active drug, 8 got an inactive placebo
  • Method: preliminary and follow-up psychotherapy, 2 day-long sessions with 2 co-therapists and an overnight hospital stay. Subjects got two doses of MDMA during each session and alternated conversation with periods where they were encouraged to focus on introspection.
  • Assessment instruments were CAPS, a structured interview, and IES-R, a self-report of response to stress. Neurocognitive testing was done and vital signs were monitored.
  • Rescue medication with Zolpidem and benzodiazepines was allowed when needed. This did not appear to influence results.
  • Protocol amendment: After safety and efficacy were established, an amendment to the protocol was approved so that the last 9 subjects received a third dose of MDMA to prolong the effect and gather data about dosage for future trials.
  • Crossover extension: 7 out of 8 subjects from the placebo group were enrolled in a subsequent open-label phase with MDMA; one declined because she had already improved so much on the placebo.
  • Exit poll: 95% correctly guessed which group they were assigned to.


  • Clinical response was defined as >30% reduction from baseline in CAPS total severity score. The clinical response was 83% in the MDMA group compared to 25% in the placebo group.
  • 100% of the 7 subjects from the placebo group who were subsequently given MDMA open-label had a clinical response.
  • All 3 subjects who had been unable to work due to PSTD were able to return to work.
  • There were no significant changes in neurocognitive tests.
  • Side effects occurred, ranging from jaw tightness to insomnia, resolving over hours or days, sometime requiring short-term drug treatment; none were felt to be serious.

Limitations of the study

This was only a small pilot study, not the kind of evidence needed to justify forging ahead with treatment of patients with PTSD. The subjects were almost all women who were rape victims. Its applicability to war trauma is entirely unknown. Further studies with combat veterans are in the works.

The study is characterized as blinded; but the blinding didn’t work, since 95% of subjects were able to tell which group they were in.

Subjects may have been influenced by the reputation of MDMA as a recreational drug that produces euphoria. MDMA is illegal, and this study required a special Investigational New Drug (IND) permit. It was financed by the Multidisciplinary Association for Psychedelic Studies.


In a 2010 news report, Mithoefer

expressed concern that publicity about the study might lead some people to self-medicate with ecstasy. PTSD patients should not use the drug on their own, Mithoefer said, because there are risks, such as elevated blood pressure and pulse. Also, ecstasy purchased on the street may not be pure MDMA — or even contain no MDMA at all.

In the NY Times article there is a quotation from Brig. Gen. Loree Sutton, a psychiatrist who recently retired from the Army:

When it comes to the health and well-being of those who serve, we should leave our politics at the door and not be afraid to follow the data.  There’s now an evidence base for this MDMA therapy and a plausible story about what may be going on in the brain to account for the effects.

That’s inaccurate; there is not an “evidence base.” There is only a pilot study with scanty, preliminary, unconfirmed evidence.

A military spokesman put the cart before the horse:

Completing the studies necessary to make this treatment available will require increasing financial and political support from both within and outside the military,” he said. “We provide men and women in the armed forces with the most advanced tools of war. It’s time we gave them the most advanced tools of healing, too.”

It’s not a matter of doing studies necessary to make the treatment available, but rather a matter of doing the studies necessary to determine whether the treatment really is effective and is a feasible option.

Other Questions

The use of another illegal drug, LSD, has been advocated by some psychiatrists for a multitude of uses. Experiments using illegal drugs are always problematic, because researchers tend to be advocates for legalization and may be biased by their emotional investment.

Prolonged exposure therapy is a widely recognized therapy for PTSD. The rationale for using MDMA is to suppress anxiety and allow patients to talk about their traumatic experiences without feeling excessive fear and hyperarousal. Various possible (and plausible) mechanisms for its usefulness are discussed in the introduction to the study. Another technique that has been used to facilitate patients’ engaging with psychotherapy is Eye Movement Desensitization and Reprocessing (EMDR), where the eye movements themselves don’t actually do anything.

The patients in the placebo group improved, too; so a large part of the benefit could be attributed to the psychotherapy.  Should the specific psychotherapy techniques they used be further investigated and improved? Was there something special about the effects of MDMA, or might legal anti-anxiety drugs be just as effective?

After WWII, soldiers suffering from “combat fatigue” were given sodium pentothal (“truth serum”) and were allegedly cured by re-experiencing the trauma.  Such treatments apparently didn’t really work that well, since they quickly fell out of favor. Most references are from the 1940’s. One flight surgeon found that distributing liquor at mission debriefings was effective at “settling” his fliers, but I don’t think that was ever formally studied.

Is it essential that patients be guided to re-live their traumatic experience? It sounds plausible, but I don’t know and doubt that anyone does. Is it possible that PTSD could be treated without that, by accentuating the positive and concentrating on avoidance and coping skills? I don’t know. Is it possible that PTSD could be prevented by early debriefings right after the event with the assistance of alcoholic beverages? I don’t know, but it’s an intriguing thought. Maybe some research group could get a grant from Jack Daniel’s.


The addition of MDMA to psychotherapy might prove helpful in refractory cases of PTSD, but the preliminary results of this one small pilot study will need to be confirmed by larger studies in combat veterans before the treatment can recommended to patients. Unfortunately, the history of medicine is full of equally promising treatments that didn’t pan out. Probably the most typical course is this: a strongly positive pilot study is followed by larger studies with weaker positive results, then by studies with equivocal or negative results, then reports of serious side effects or other problems, and eventually by rejection of the treatment. I sincerely hope this one will prove an exception to that course, for the sake of suffering veterans with few remaining options. But I am not optimistic.



Posted in: Clinical Trials, Neuroscience/Mental Health

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