The Food and Drug Administration has issued a comprehensive rejection letter to Lykos Therapeutics, detailing serious flaws in the company’s application to approve MDMA as a treatment for post-traumatic stress disorder. The document reveals troubling gaps in safety data collection, study design problems, and methodological concerns that undermine the reliability of the clinical trial results.
Missing Safety Data
The FDA identified a critical failure in data collection. Lykos did not gather information on events that participants, therapists, or study physicians considered positive or favorable. This information would have been essential for assessing the drug’s abuse potential and patient impairment during clinical trials. The agency also discovered unreported adverse events at multiple study sites through its inspections, further calling into question the reliability of the safety data submitted.
The FDA had specifically advised Lykos to capture all relevant events, regardless of whether they appeared neutral, positive, or favorable. The company’s failure to follow this guidance means regulators cannot adequately assess the safety profile of midomafetamine (the pharmaceutical name for MDMA) for PTSD treatment.
Questions About Treatment Duration
The clinical trials failed to demonstrate whether the observed effects lasted beyond 18 weeks after treatment began. Since PTSD is a chronic condition, any approved drug would need to show durable treatment effects. The proposed dosing regimen consisted of just three treatment sessions over a limited period, making it crucial to understand whether benefits persist over time. The short assessment window raises questions about the long-term viability of this treatment approach.
Study Population Concerns
Approximately 40% of enrolled participants reported prior use of MDMA, a rate significantly higher than the background use in the PTSD population. National Survey on Drug Use and Health data from 2022 showed lifetime MDMA prevalence of only 16.2% to 20.5% among individuals with moderate or severe mental illness. The high rate of prior drug use among study participants, combined with very high failure rates during prescreening, suggests possible selection bias.
This mismatch between the study population and the broader PTSD population limits how broadly the results can be applied. Additionally, participants with prior MDMA experience would more likely recognize the drug’s effects, leading to functional unblinding. When people know whether they received the active drug or a placebo, study results can overstate efficacy and understate risks.
Recommendation for Independent Audit
Given the severity of concerns about data reliability, the FDA recommended that Lykos consider an independent third-party audit of all study records and reports, including recordings of treatment sessions. This suggestion reflects the agency’s lack of confidence in the data emerging from these trials.
Incomplete Testing
The application lacked laboratory data from Phase 3 studies, including liver analytes and electrolytes. The cardiac safety assessment was also incomplete. These omissions represent significant oversights in the safety evaluation process.
Additional Study Design Issues
The FDA noted that the trial design made it difficult to determine whether treatment benefits came from the MDMA itself or from the psychotherapy administered alongside the drug. The agency recommended a factorial study design that includes an arm without psychotherapy to isolate the drug’s effects.
The study also failed to achieve adequate population diversity, which further limits the generalizability of any findings. This falls short of recent FDA guidance on improving enrollment of participants from underrepresented populations.
Required Additional Studies
The FDA outlined several additional studies that would be necessary:
- A drug interaction study with SSRI medications to determine whether patients need to taper off these common antidepressants before starting MDMA treatment.
- Pharmacokinetic studies in patients with impaired liver function, since MDMA is primarily metabolized in the liver.
- Studies in patients with severe kidney impairment to understand how reduced kidney function might affect drug disposition.
- A clinical lactation study to determine how much MDMA passes into breast milk.
- Pre- and postnatal development studies to characterize risks during pregnancy, particularly to the developing central nervous system.
Broader Implications for Psychedelic Research
The rejection letter highlights problems that extend beyond Lykos. A 2024 review of nearly 200 published psilocybin studies and 80 ongoing ones found similar methodological weaknesses across the field. Almost half of the studies examining psilocybin did not use a control group. The median number of study participants was only 22, with a median of 18 actually taking the drug. Nearly 40% relied on self-reporting and questionnaires rather than objective clinical measures for their primary outcome assessments.
These patterns suggest systemic issues in psychedelic therapy research, where advocacy appears to have outpaced rigorous scientific methodology. The FDA’s detailed critique of Lykos serves as a warning about the need for more robust research standards before these substances can be approved as medical treatments.
Company Background
Lykos Therapeutics was spun out of the Multidisciplinary Association for Psychedelic Studies (MAPS), a nonprofit founded by psychedelic drug advocate Rick Doblin. The company had generated significant media attention when the FDA advanced its product through Phase 3 trials. However, an advisory panel later voted overwhelmingly against approval, citing doubts about both efficacy and safety. The situation worsened when papers promoting MDMA’s efficacy for PTSD were retracted due to ethical violations, including an alleged sexual assault committed by a therapist against a participant during Phase 2 trials.
The comprehensive rejection letter makes clear that substantial additional work would be required before MDMA could be considered for approval as a PTSD treatment. The document stands as a detailed case study in the importance of rigorous clinical trial design and transparent safety data collection.
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