FDA Releases Complete Response Letter on Declining MDMA-Assisted Therapy for PTSD

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The US Food and Drug Administration (FDA) has publicly released a Complete Response Letter (CRL) to Lykos Pharmaceuticals, making public for the first time the details of their decision to decline approval of MDMA-assisted therapy for individuals with posttraumatic stress disorder (PTSD).^1,2 Lykos Pharmaceuticals previously received the FDA decision to decline approval of the treatment in August of 2024, and the CRL was only released publicly this week.³ This particular case comes with a move by the FDA to release 89 previously unpublished CRLs and begin releasing future CRLs to the public immediately after issuing them to sponsors.⁴

Releasing previous CRLs marks a shift towards public transparency in drug approval decisions by the FDA. Previously issued CRLs will be posted publicly, all new CRLs will be promptly shared, and CRLs from prior withdrawn applications will be shared.⁴ This is the first time the FDA has provided such a level of transparency regarding their decision making.

MAPS, the Multidisciplinary Association for Psychedelic Studies, while not working directly with the FDA, held a press briefing to further discuss the contents of the CRL on rejection of MDMA-assisted therapy for PTSD. Rick Doblin, PhD, founder and president of MAPS, said in the briefing that there was “a changing of the goalposts” by the FDA, as the CRL noted study design issues that had not been marked during their extensive “discussions with FDA about every single aspect of the protocol design” in the Special Protocol Assessment process.⁵ According to Doblin, researchers had worked with the FDA to create an effective double-blind study design, as the design is notoriously difficult when working with psychedelic drugs. Doblin also pointed out that the FDA’s letter did not address the amendment that Lykos submitted addressing previous issues.

Doblin outlined the conversations between researchers and the FDA in designing the study, emphasizing that design elements initially recommended during the special assessment were noted as issues in the CRL. The FDA had recommended not using a low dose comparison arm, and instead using a placebo group, but then wrote in the CRL to “consider the inclusion of a low-dose midomafetamine arm as a control.”² The letter also cited lack of durability of treatment and concerns about participants having prior experience with MDMA use. Doblin pointed out that in the study results, there were no significant differences between patients with prior MDMA use experience and patients who has no prior experience.⁵

The statement from MAPS added that “Lykos will continue negotiations with the FDA. MAPS will keep driving forward: incubating and accelerating new MDMA-focused research, training therapists around the globe, catalyzing humanitarian projects in high trauma/low resource areas of the world, and building the infrastructure for a future where psychedelic-assisted healing and personal growth is not delayed by shifting politics, but delivered as a matter of compassion and justice.”¹

References

1. MAPS statement on FDA’s public release of Complete Response Letter for MDMA-assisted therapy. Press release. September 4, 2025. Accessed September 5, 2025. https://www.morningstar.com/news/globe-newswire/9523929/maps-statement-on-fdas-public-release-of-complete-response-letter-for-mdma-assisted-therapy

2. Complete Response, NDA 215455. US Food and Drug Administration. August 8, 2024. Accessed September 5, 2025. https://psychedelicalpha.com/wp-content/uploads/2025/09/CRL_NDA215455_20240808.pdf

3. Duerr, HA. FDA issues CRL to Lykos for MDMA-Assisted Therapy. Psychiatric Times. August 9, 2024. https://www.psychiatrictimes.com/view/fda-issues-crl-to-lykos-for-mdma-assisted-therapy

4. FDA announces real-time release of complete response letters, posts previously unpublished batch of 89. News release. US Food and Drug Administration. September 4, 2025. Accessed September 5, 2025. https://www.fda.gov/news-events/press-announcements/fda-announces-real-time-release-complete-response-letters-posts-previously-unpublished-batch-89

5. MAPS Media Briefing: FDA Publishing Lykos CRL. Press briefing. MAPS. September 5, 2025.