In a stunning decision, an FDA-appointed advisory committee, comprised of 11 independent experts, rejected MDMA-Assisted Therapy as a treatment for PTSD, voting that the evidence for both its effectiveness and safety is insufficient.

This expert advice is not binding, but it does decrease the likelihood that the FDA will approve MDMA-Assisted Therapy for clinical use in early August. 

As one of the last steps before making its final decision, the FDA formed an advisory committee to review and assess the effectiveness and safety of MDMA-Assisted Therapy. The experts were provided with all the available research data, the list of the FDA’s concerns about the MAPS studies, and the FDA’s proposal for rolling out this novel treatment if approved, including a detailed Risk Evaluation and Mediation Strategy (REMS). The experts were also provided with statements from the general public, other experts, the American Psychiatric Association, and some participants from the MAPS studies. The experts had ample opportunities to ask questions and to comment and deliberate. 

At the end of the meeting, the experts voted 10:1 that the potential risks of MDMA-Assisted Therapy outweighed the potential benefits, and 9:2 that the evidence for the effectiveness of this treatment was insufficient. 

I am still stunned, as I imagine are many others. It seems unthinkable that after years of careful collaborative effort between the FDA and MAPS, the sweat of so many people, the positive coverage in the media, and several scientific publications in respectable journals showing unprecedented results in terms of effectiveness and a good safety profile for this therapy, this committee rejected outright MDMA-Assisted Therapy as a treatment for PTSD. 

So what went wrong? Were the flaws in the MAPS research significant enough to discredit the results? Was the major ethical violation during the MAPS earlier trail a determining factor? Was the FDA insufficiently diligent when co-designing these studies with MAPS? Was this group of experts sufficiently unbiased and free of conflict of interests? Was the Power Trip Podcast and the recent ICER report that built on that podcast the catalyst for this rejection? Does any of this have to do with the fact that it is the first time a drug and psychotherapy are to be used together? Is our culture not ready for what might be a major change in mental health treatment? Is it something else altogether?

To attempt to answer these questions properly, one would have to analyse in detail all the available information and the meeting itself. I watched a part of the meeting and read the minutes. There are a lot of details there, and at this point, I do not feel it is my place to provide this sort of comprehensive analysis. I very much look forward to being enlightened on what just transpired by those who are more informed. 

However, to contribute to what will likely be a lively debate between now and August, I would like to make two broad observations. 

First, regarding safety, it is worth noting that, while the FDA clearly voiced its concerns and clearly stated that the approval of this application is not guaranteed, they also stated that their concerns might be able to be 1) further addressed during the post-approval process and 2) mitigated with a REMS. In fact, the FDA presented a comprehensive REMS which I thought was excellent and very stringent with regards to maximizing safety. The panel, however, did not seem to agree that the FDA’s plan was sufficient for assuring safety. 

As to the effectiveness, I would like to point out the most obvious. The effect size of this treatment (which is an indicator of the size of the improvement in symptoms) was very large. In fact, it was unprecedented when compared with any other treatment method for PTSD. Such a large effect size has a lot of margin for error, so even if the missing outcome data was less favorable, and even if there was bias related to unblinding and expectancy effects, the effect size for MDMA-Assisted Therapy would still likely be very large. We should not lose sight of that very important fact given the desperate need for a good therapy for trauma. 

In the end and most importantly, if MDMA-Assisted Therapy is approved for clinical treatment for trauma, the benefits of this therapy have to greatly outweigh the risks. I do not know anyone in the field who disagrees with this statement. And now it is in the hands of the FDA to weigh out those risks and benefits. And no matter the outcome, I hope this will be done with utmost objectivity.

* Note that MDMA is illegal and MDMA-Assisted Therapy is not approved for any use at this time. We do not encourage or condone the use of MDMA in any context.