The Obstacles Associated with Approving Psychedelic Therapies

Editor’s note: The following story highlights the impact of the FDA’s decision not to approve MDMA-assisted therapy. Read more about the clinical trial here.  

On August 9^th, 2024, the U.S. Food and Drug Administration (FDA) formally rejected the approval of MDMA-assisted therapy for the treatment of post-traumatic stress disorder (PTSD). In response to the new drug application (NDA) submitted earlier this year by the pharmaceutical company, Lykos Therapeutics, the FDA issued a Complete Response Letter (CRL) detailing the reasons for the rejection of this potential therapeutic.

This decision has shaken the psychedelic research community and left hopeful patients suffering from PTSD without new treatment options.

While the CRL has not been released to the public, Lykos released a statement addressing some of the FDA’s concerns. Echoing the concerns brought up at a previous Advisory Committee meeting, the FDA concluded that the evidence supporting MDMA’s efficacy for treating PTSD was insufficient. In particular, the FDA raised questions regarding the challenges associated with combining a drug treatment with psychotherapy as well as bias within the design of the clinical trials. These concerns have been described in detail in a previous blog post. The CRL culminated in the FDA’s request for an additional phase 3 clinical trial, a huge ask for Lykos. 

"The FDA concluded that the evidence supporting MDMA’s efficacy for treating PTSD was insufficient. In particular, the FDA raised questions regarding the challenges associated with combining a drug treatment with psychotherapy as well as bias within the design of the clinical trials."

-- Anna Tsyrulnikov

Since this decision came out, responses from involved parties have been substantial. The scientific journal that originally published multiple papers from Lykos’ clinical trials, Psychopharmacology, retracted three papers on MDMA-assisted therapy from the company’s phase 2 trials. The editors of Psychopharmacology stated that the articles were retracted due to “protocol violations amounting to unethical conduct,” that occurred during the phase 2 clinical trials.

As part of Lykos’ response to the article retractions and the FDA’s rejection, the company will be reducing their workforce by 75% in order to focus on “clinical development, medical affairs, and engagement with the FDA.” Lykos also announced that Rick Doblin, the founder and executive director of the Multidisciplinary Association for Psychedelic Studies (MAPS), has stepped down from his board position. MAPS was rebranded as Lykos at the beginning of 2024.

With this structural reorganization, Lykos plans to proceed with a resubmission of an NDA. Simultaneously, many other pharmaceutical companies are currently working to advance their own clinical trials in hopes of being the first to earn FDA approval for a psychedelic-assisted therapy. Some of these companies have opted to exclude psychotherapy from their drug treatment model, which would avoid the complications involved in its regulation. However, it’s still unclear how crucial psychotherapy is for the efficacy of psychedelic treatments.

Even as obstacles have arisen recently, it’s unreasonable to discredit the overwhelming amount of data that continues to support a therapeutic role of psychedelics. This rejection emphasizes the importance of transparency and objectivity for practicing ethical science.