A Review of the Federal Drug Administration Pipeline and Proposed California Legislation on Medicinal Psychedelics

Title & Introduction

• Paper Title: A Review of the Federal Drug Administration Pipeline and Proposed California Legislation on Medicinal Psychedelics
• Published In: The Permanente Journal
• Publish Date: February 21, 2025
• Authors: Jack R. Watson, Laura Halpin, Violeta Barroso, George Dahdouh, Jacqueline Bursalyan, Saahil Mohta, Michelle Flores, Natalie Gonzalez, John Gordineer, Germain Medina, Crystal Oseguera, Jailene Lazaro Serrano
• Objective: To review the FDA pipeline for psychedelic-assisted therapy, including late-stage clinical trials, and to compare this process with California’s recent legislative attempts to expand access to psychedelics.
• Importance: As psychedelic research advances, understanding the regulatory landscape helps balance access to emerging therapies with patient safety concerns.

Summary & Takeaways

Key Takeaway:
The FDA remains the primary agency for evaluating psychedelic therapies, but California’s legislative efforts could offer alternative pathways to access. However, concerns over safety, trial rigor, and regulatory oversight persist.

Practical Application:
Stakeholders in psychedelic research and policymaking should weigh the benefits of FDA-approved trials against state-level decriminalization and therapeutic access efforts to ensure patient safety and drug efficacy.

Key Background Information

• Context: Psychedelic-assisted therapy is undergoing regulatory scrutiny in the U.S. The FDA’s pipeline includes several phase 3 trials, while California has attempted but failed to pass legislation allowing broader access to psychedelics.
• Hypothesis: The FDA’s rigorous approval process ensures safety and efficacy, while state-led legislative efforts provide alternative but potentially riskier pathways to access.

Methodology

• Study Design: Policy and clinical trial analysis.
• Participants: Not applicable (regulatory review).
• Intervention/Exposure: Review of FDA psychedelic trials and California legislative proposals.
• Controls: Not applicable.
• Duration: Data collected through 2024.

Key Findings

Primary Outcomes:

• As of 2024, there were 7 FDA phase 3 trials:
  • 2 for ketamine (alcohol use disorder and post-comatose disorders of consciousness).
  • 5 for psilocybin (major depressive disorder, treatment-resistant depression, and frontline clinician burnout).
• The FDA denied Lykos Therapeutics’ new drug application for MDMA-assisted therapy for PTSD, citing study design flaws and safety concerns.
• Psychedelic safety concerns include serotonin syndrome, addiction potential, and reports of increased suicidality with LSD use.
• California’s Senate Bills 58, 1012, and 803 attempted to expand access to psychedelics but failed due to safety concerns and regulatory challenges.
• The VA announced its first federally funded psychedelic study in 60 years, examining MDMA for veterans with PTSD and alcohol use disorder.

Secondary Outcomes:

• Ketamine showed promise in alcohol use disorder treatment, with phase 2 trials reporting increased abstinence rates.
• Psilocybin phase 3 trials focus on its use in depression and burnout, with early results indicating symptom reduction.
• Functional unblinding remains a challenge in psychedelic trials, leading to potential expectation bias.
• Cost remains a major barrier, with full FDA approval requiring millions of dollars in research funding, whereas state-level legislation is significantly less expensive to implement.

Interpretation & Implications

• Conclusion: While state legislative efforts may facilitate access, the FDA’s role in ensuring rigorous safety and efficacy testing remains crucial. Psychedelic therapies should be integrated into regulatory frameworks that maintain patient safety.
• Implications: Policymakers should focus on funding rigorous research rather than bypassing FDA processes. The VA’s involvement in psychedelic research could set a precedent for federal expansion.
• Limitations: This review does not include patient-reported outcomes from psychedelic therapy, and further research is needed to assess long-term safety concerns.

Researchers & Publication

• Researchers: Jack R. Watson, Laura Halpin, Violeta Barroso, George Dahdouh, Jacqueline Bursalyan, Saahil Mohta, Michelle Flores, Natalie Gonzalez, John Gordineer, Germain Medina, Crystal Oseguera, Jailene Lazaro Serrano
• Publication Name: The Permanente Journal
• Study URL: https://doi.org/10.7812/TPP/24.171