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FDA Publishes MDMA CRL, Exposes Safety and Durability Concerns for Psychedelic Therapies

by | Sep 22, 2025 | FDA, Harm Reduction, MDMA, Mental Health, policy, politics, Science, Therapy, Veterans

Government document with FDA letterhead, overlaid with a subtle photo of a clinical trial site.

FDA Publishes MDMA CRL, Exposes Safety and Durability Concerns for Psychedelic Therapies

The US Food and Drug Administration announced on September 4, 2025 that it will publish Complete Response Letters promptly after they are issued, and it released a batch of 89 previously unpublished CRLs. Included in that tranche is the CRL issued to Lykos Therapeutics that declined approval of an MDMA-assisted therapy application for PTSD, a move that materially shifts regulatory transparency in the psychedelic medicine landscape (https://www.fda.gov/news-events/press-announcements/fda-announces-real-time-release-complete-response-letters-posts-previously-unpublished-batch-89).

 

Key findings from the Lykos CRL

The CRL highlights three main concerns: gaps and potential underreporting in safety data, insufficient evidence of durability for a chronic disorder like PTSD, and trial selection issues tied to high rates of prior MDMA use among participants. The FDA suggested independent data audit and additional trials to resolve these issues (https://psychedelicalpha.com/news/breaking-fda-publishes-lykos-therapeutics-mdma-complete-response-letter-crl).

Why this matters for developers and clinicians

Public CRLs mean sponsors must assume that trial design weaknesses, safety reporting gaps, or manufacturing concerns could be disclosed, with reputational and financial consequences. Agencies and legal advisors are already updating best practices to reflect this new reality (https://www.lw.com/en/insights/fda-publishes-complete-response-letters-for-unapproved-drug-applications).

 

Practical next steps

  • Strengthen adverse event capture and site monitoring now, and plan for independent data audits if requested. See the CRL recommendations for precedent (https://psychedelicalpha.com/news/breaking-fda-publishes-lykos-therapeutics-mdma-complete-response-letter-crl).
  • Design trials to demonstrate durability of effect for chronic conditions, including longer follow-up windows and pre-specified durability endpoints.
  • Reduce selection bias through stratified enrollment plans and clear disclosure of prior-use prevalence in protocols and labeling discussions.

 

Field reactions

MAPS praised the FDA’s transparency, but accused the agency of moving the goalposts after trial completion, arguing that delays hurt patients living with PTSD (https://maps.org/2025/09/04/fda-public-release-of-crl/). FDA Commissioner Marty Makary framed the policy as a milestone for transparency and public trust (https://www.fda.gov/news-events/press-announcements/fda-announces-real-time-release-complete-response-letters-posts-previously-unpublished-batch-89).

In short, the FDA’s public CRL policy and the Lykos MDMA letter force the psychedelic field to prioritize auditable safety, demonstrable durability, and robust trial design before approval is possible.

 

Related internal links

 

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