Client Alerts  - Psychedelics and Mental Health Therapeutics Apr 29, 2024

A Recent FDA-Sponsored Meeting Addressed Psychedelic Drug Development, Including the Limits of FDA’s Regulatory Authority

Meeting Offered Valuable Insights on Psychedelic Drug Development and Research

On January 31 and February 1, 2024, the Reagan-Udall Foundation for the U.S. Food and Drug Administration (FDA) held a virtual public meeting, “Advancing Psychedelic Clinical Study Design,” which addressed key issues in psychedelic drug development and research.1

Recent years have witnessed a significant resurgence of interest in the therapeutic potentials of psychedelic substances. This revival is marked by a growing body of research exploring the efficacy of psychedelics — a catch-all term used in the FDA-sponsored public meeting to include classical psychedelics such as psilocybin and LSD as well as enactogens such as MDMA — in treating various mental health conditions, including depression, post-traumatic stress disorder (PTSD) and substance use disorders. The meeting underscored this burgeoning interest, bringing together stakeholders from regulatory bodies, the research community and the public to discuss the scientific and regulatory challenges that come with this territory.

The meeting included an overview of the FDA’s draft guidance, “Psychedelic Drugs: Considerations for Clinical Investigations,”2 issued in June 2023, that provided general considerations across various disciplines for drug development programs. It also emphasized the unique challenges that psychedelic substances pose, such as intense perceptual disturbances and alterations in consciousness, which necessitate careful consideration in clinical study design to ensure interpretable results. Other areas covered at the meeting included topics on blinding, dosing, durability of treatment response, set and setting, limitations of the FDA regulatory authority, and considerations for real world use.

Each of the sessions provided valuable insights for psychedelic researchers and stakeholders interested in psychedelic drug development as well as for providers and health care institutions interested in interpreting the research and planning for potential rollout should psychedelics receive FDA approval.

Both the meeting discussions and the FDA guidance highlighted several challenges inherent in conducting clinical trials with psychedelics. These challenges include blinding issues due to the distinctive psychoactive effects of psychedelics, which can lead to functional unblinding and, consequently, influence study outcomes. Psychedelics are often administered in conjunction with psychotherapy, which complicates the assessment of their standalone therapeutic effects. The FDA’s guidance suggests a need for trials to carefully delineate the contributions of the drug versus the psychotherapeutic interventions to understand the true efficacy of the treatment regimen. The agency emphasizes the need for innovative trial designs that can adequately address these issues while providing robust data on the drug’s safety and efficacy.

Although knowledge of the FDA’s regulations is important, equally important is a thorough understanding of the FDA’s regulatory authority limits. A session from the public meeting— “Limitations of FDA’s Regulatory Authority,” presented by Dr. Tiffany Farchione, Director of the Division of Psychiatry at the Center for Drug Evaluation and Research at the FDA—provided an informative discussion on this topic.3

Dr. Farchione discussed two aspects — especially relevant to psychedelics — that the FDA does not regulate: psychotherapy and the practice of medicine.

Dr. Farchione noted that psychotherapy is not just a confounding factor but could potentially act as an integral component of a psychedelic medication’s safety and efficacy profile. However, within the context of a psychedelic intervention, there is no rigorous definition of what exactly the psychotherapeutic portion entails. This complicates the FDA’s assessments of the drug and future product labeling. She also pointed out that the assumption that psychotherapy is a necessary component in a psychedelic intervention has not been rigorously tested. According to Dr. Farchione, well-done factorial studies — studies that address more than one intervention and which are unfortunately large and costly — would be highly informative in helping to determine the contributions of psychotherapy to the safety and efficacy of a psychedelic medication and would assist in creating better product labels.

Dr. Farchione discussed that the Code of Federal Regulations allows the FDA to specify if a medication should be used only in conjunction with another mode of therapy and included a slide with a table (shown below) showcasing the somewhat abbreviated nature of the psychotherapy-type language in the product labeling for several FDA-approved medications.

Chart from “Advancing Psychedelic Clinical Study Design,” Reagan-Udall Foundation for the FDA, February 2024

Chart adapted from: “Advancing Psychedelic Clinical Study Design,” Reagan-Udall Foundation for the FDA, February 2024.

She noted that if the FDA is going to specify that a psychedelic should only be used in conjunction with a primary mode of therapy, “we probably ought to know if that mode of therapy is necessary.”4

Regarding the practice of medicine, Dr. Farchione pointed out that many of the psychedelic therapy aspects of set (often defined as the patient’s mindset and expectations) and setting (often defined as the physical and social environment) are outside the FDA’s regulatory authority. She also discussed that, while a drug safety program called REMS (Risk Evaluation and Mitigation Strategy) — which the FDA can require for certain medications with serious safety concerns — might be able to address some of the safety components of the psychedelic sessions by notifying, educating or enforcing actions to decrease the frequency or severity of the risk(s), a REMS is not intended to address efficacy. As such, a REMS would not be able to address aspects of psychotherapy or treatment settings related to efficacy. However, given the novel and potent nature of psychedelic drugs, the FDA is likely to implement stringent post-market surveillance requirements to monitor the drugs’ real-world efficacy and safety.

In addition, while the FDA has authority to mandate the monitors’ credentials in clinical trials, the FDA would not have the same authority post-marketing; the regulation of the monitors’/therapists’ credentials would likely fall under state medical boards or other state-level authorities.

Although the FDA approves a medication for a specific indication, prescribers can use the medication to treat a different condition(s) because this falls under the practice of medicine, which the FDA does not regulate. As such, “off-label” prescribing is not regulated by the FDA. However, the FDA is able to take regulatory action against companies who use information not included in the product label to promote “off-label” use.

Understanding the limits of the FDA’s regulatory authority will help not only drug developers and researchers in clinical trial designs of psychedelics but will also assist all stakeholders in the psychedelics space to plan and prepare for the real-world use of psychedelic medications if they receive FDA approval.

Finally, ethical concerns particularly around informed consent and the potential for long-lasting psychological impacts are critical for the FDA. Researchers must navigate these ethical waters carefully to protect participants. Ensuring the safety of participants in psychedelic trials is paramount. Continuous monitoring during and after the administration of psychedelics is necessary to manage adverse effects and ensure patient safety. The agency will likely require detailed plans for how these ethical and safety issues are managed within clinical trials and in subsequent clinical practice.

The FDA’s approach to approving psychedelic drugs is marked by an acute awareness of the unique challenges these substances present. From trial design to post-market regulation, the agency’s key concerns revolve around ensuring that the therapeutic benefits of psychedelics are realized safely and ethically within a well-regulated clinical framework.

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1 Advancing Psychedelic Clinical Study Design Virtual Public Meeting, Reagan-Udall Found. for the FDA, (last visited Apr. 25, 2024).

2 Psychedelic Drugs: Considerations for Clinical Investigations (June 2023), FDA,

3 Tiffany R. Farchione, Dir., FDA Div. of Psychiatry, Off. of Neuroscience, Limitations of FDA’s Regulatory Authority in Advancing Psychedelic Clinical Study Design Virtual Public Meeting Day 2 slides at 71, (Feb. 1, 2024)

4 Day 2: February 1, 2024 Transcript at 21, Advancing Psychedelic Clinical Study Design Virtual Public Meeting, Reagan-Udall Found. for the FDA,