On August 9, 2024, the FDA rejected the application for MDMA-assisted therapy to become an approved treatment for PTSD. The FDA’s decision came as a shock to many who have worked to bring this promising treatment to patients in need. How can the entire world go from believing that this is the solution to all the world’s problems to believing that it was all just nonsense? Despite extraordinary clinical results demonstrating efficacy, the rejection highlights the scientific, cultural, and bureaucratic obstacles that still stand in the way of psychedelic therapy. To me, it seems that most of the writing around this is very superficial, thin, and unbalanced. I have followed this process and listened to critics of MAPS and key people in the process. Here is a review of the main reasons for the rejection, based on my understanding of it:
1. Challenges with double-blind design
One of the points of rejection was that participants could guess whether they were receiving MDMA or not. One of the biggest challenges in the studies was ensuring that participants and researchers remained “blind” to which treatment was being given. MDMA produces distinct physical and emotional effects, which made it easy for most participants and therapists to understand whether they were receiving MDMA or a placebo.
Attempts to solve this, such as using low doses of MDMA as an active placebo, led to other problems. Participants who received low doses often experienced discomfort, and their results were worse than those who received placebo. This highlighted the difficulty of balancing blinding and therapeutic effect, which became a central focus of FDA criticism. MAPS (now Lykos) has been discussing this with the FDA for several years and they came up with a solution that they both believed was as good as possible.
2. Changes in regulatory expectations
At the beginning of the process, MAPS and the FDA had reached an agreement on how the studies would be conducted. MAPS’ MDMA study was given “Breakthrough Therapy” status by the FDA, which meant that MAPS and the FDA would collaborate and adjust the protocol on an ongoing basis to ensure faster approval. However, when new people took over the leadership of the FDA’s Psychiatry Division, several requirements were changed. For example, stricter requirements were introduced that lead therapists must have MD or PhD degrees, and that a physician must be physically present during sessions instead of just being available, as was the case before.
These requirements had no clear support in research data to improve safety or effectiveness, but rather seemed like an expression of caution. These changes increased costs and further delayed the process.
3. Negative media narratives
While MAPS and Lykos focused on working with the FDA in the final stages of filing, they chose to enter a “silent media phase,” which meant they failed to address criticism in the media. They believed it was a sham and that the media would not influence the FDA’s assessment. Critical articles, particularly from an organization calling itself Psymposia (which is also outspokenly against the commercialization of psychedelics), raised doubts about the study design, treatment protocols, and safety of MDMA, despite solid clinical evidence to the contrary.
A major mistake was not to highlight positive news during this period, such as the Dutch State Committee’s review of the same data. The committee in the Netherlands concluded that MDMA treatment was effective and safe, and recommended that it be used in controlled settings for PTSD. Without such positive counter-narratives, criticism dominated the public picture.
4. FDA and skepticism about psychotherapy
The FDA approves medications and has never before approved a protocol that combines medication and psychotherapy. MDMA-assisted therapy relies on a specific therapeutic protocol, which the FDA has proven uncomfortable reviewing. The agency questioned whether the therapy alone could explain the results, despite decades of data demonstrating MDMA's unique therapeutic potential.
This misunderstanding of the interaction between the substance and the therapy became a key factor in the refusal.
5. Public skepticism about commercial collaborations
MAPS faced criticism for its collaboration with Lykos, a commercial entity created to fund and scale clinical trials. Critics claimed that MAPS had “sold out,” and this distrust helped to undermine confidence in the process.
However, this collaboration was necessary to meet the financial demands of the approval process. Such costs – typically billions of kroner – typically exceed what can be raised through donations alone. Yet the partnership was often misunderstood as an ethical issue, and this weakened public support.
6. Political and bureaucratic obstacles
Despite significant progress in reducing the stigma surrounding psychedelics, cultural and political barriers still exist. Some members of the FDA advisory committee expressed concern about the broader societal consequences of such approval.
In addition, lower levels of the FDA appear to be more inclined to reject controversial treatments, partly for fear of being held accountable for potential negative outcomes. The FDA has come under fire in recent years, including for approving the Alzheimer's drug Aduhelm and the painkiller Vioxx, which was pulled from the market after it was found to increase the risk of heart attacks and strokes. It has also been heavily criticized for its handling of the OxyContin crisis in the United States. Increased institutional caution also likely contributed to the decision.
The way forward for MDMA-assisted therapy
The rejection is a setback, but it is not the end. MAPS and Lykos are already considering how to address the FDA's concerns and conduct the necessary additional studies. At the same time, international developments provide hope. In the Netherlands, authorities have already moved forward with recommendations for the use of MDMA therapy in controlled settings, and Australia has already approved both psilocybin and MDMA for strictly regulated clinical use.
The decision also underscores the need for public education and cultural engagement. MAPS and others in the field must work to regain control of the media narrative and ensure that both the public and policymakers understand the solid evidence supporting MDMA-assisted therapy and the life-changing impact it can have.
The road to approval may be longer than expected, but the goal remains the same: to make MDMA-assisted therapy a widely available, evidence-based treatment for PTSD. So now the journey continues, not just in the lab, but also in the public sphere, where culture and science meet to shape the future of medicine.