Rick Doblin Responds to Ecstasy to Treat PTSD? Not So Fast

Originally appearing here. I’m the Executive Director of MAPS. Kent says anything I say should be discounted because of bias. That’s a valid point, and it’s why scientific methodology is so important, to reduce conscious and unconscious experimenter bias. That’s why the outcomes from our initial MDMA/PTSD study were evaluated by an independent rater who administered the measure of PTSD, the CAPS, in a blinded manner and who had no prior relationship with MAPS and no vested interest in MDMA. That’s why our research was peer-reviewed before it was published in a reputable scientific journal. As for bias, Kent seems to have been so motivated to critique our initial study that he misread our abstract and reported an incorrect claim that our statistical analysis was not significant. Here is what our abstract reported, “The rate of clinical response was 10/12 (83%) in the active treatment group versus 2/8 (25%) in the placebo group.” In other words, 83% of the subjects who received MDMA, who had suffered from PTSD for over 19 years on average and had failed to respond to both psychotherapy and pharmacotherapy, no longer were diagnosed with PTSD after treatment with MDMA-assisted psychotherapy. The response rate is 83%, that’s not a measure of statistical significance. Kent subtracted 83 from 100 and came up with .17 as our measure of statistical significance, completely mistaken. If Kent had taken more than a few minutes to read the abstract and thought about what it actually reported, or if he had decided to read the actual paper, or even part of it, he would have learned that we reported that the difference between a response rate of 83% in the MDMA group and 25% in the placebo group (whose subjects received our extensive psychotherapy but with an inactive placebo) was significant (0.013). The paper can be downloaded from the MAPS website for those who want to get into the details. In addition, of the 8 subjects who initially received our therapy with an inactive placebo, 7 volunteered to go through the study again with active MDMA in an open-label manner, meaning there was no double-blind, everybody knew MDMA was going to be administered. Of those 7, 6 were those who had not obtained a clinical response. The other 1 was from the 2 responders, but whose PTSD symptoms had returned shortly after the initial follow-up evaluation was conducted two months after the last experimental session. Of these 7 subjects, all, meaning 100%, were responders who were no longer diagnosed with PTSD after the treatment. Our Swiss MDMA/PTSD study results had the same effect size as our US results, but came from a study of 12 subjects rather than 20 subjects. The Swiss results were clinically significant, meaning that subjects received meaningful benefits, and were almost statistically significant (0.066) and would have been statistically significant if the study had been in 20 subjects. The Swiss study was designed to help us determine effect size across studies and to test whether we could achieve a successful double-blind using an active placebo of low-dose MDMA (25 mg followed an average of 2 hours later by 12.5 mg). We chose to study 12 subjects since MAPS lacked the funds to make the study larger and because obtaining statistically significant results was not a priority for this study, whose goal was to help gather information necessary for the design of our eventual Phase 3 studies that will be designed to gather statistically significant information about safety and efficacy. If Kent had read our paper about our initial US study, a valid criticism would have been that the double-blind was not successful, subjects and therapists were able to guess whether an inactive placebo or full-dose MDMA had been administered. We used an inactive placebo at the request of FDA so that we would get a base measure of side effects from our psychotherapy alone. In our Swiss study, the double-blind was effective. In our initial US study, in subjects with chronic, treatment-resistant PTSD for an average of over 19 years, the failure of the double-blind is not likely to be the cause of the successful treatment outcomes. Our current long-term follow-up study, that showed that the therapeutic outcomes persisted on average for an average of over 3 1/2 years, adds further evidence that our therapy itself was responsible for the treatment outcomes, since placebo responses are more likely to fade over time, as we found in 1 of the 2 subjects who had initially responded to our therapy but relapsed shortly after the two-month follow-up. In his concluding sentence, Kent says that we were cruel. He wrote, “Though the information is released in the name of kindness, disclosure of vague results gathered vaguely is, in the long run, not humane at all, but cruel.” Our results were not vague, were not gathered vaguely, and were remarkably promising. What is cruel is misreading an abstract in a rush to say something critical, not reading the paper itself, and making false accusations about a promising treatment. Where Kent is correct is that these are small, preliminary studies. We are only in the Phase 2 stage of pilot studies and are several years away from our “End-of-Phase 2” meeting with the FDA to plan our Phase 3 studies, which are designed to gather conclusive evidence of safety and efficacy. We urge Kent to keep paying attention, though more carefully, since we welcome critical feedback as we try to conduct the most methodologically rigorous studies that we can design. Furthermore, if any other sponsor wishes to fund MDMA/PTSD research, we will permit them to cross-reference our data at FDA so that they can start directly working with people suffering from PTSD. We welcome other sponsors getting involved in this area of research. MAPS Executive Director Rick Doblin corrects The Daily Beast author Kent Sepkowitz’s inaccurate claims about research into treating PTSD with MDMA-assisted psychotherapy by providing factual, scientific information.