Perspective: FDA moving in the right direction with psychedelic drug guidance

The US Food and Drug Administration’s (FDA) recent guidance on psychedelic drug development is a “policy landmark” and a step in the right direction yet there is room for improvement in areas related to psychological support and adverse event reporting, according to a new perspective published in the New England Journal of Medicine.

The authors -- Mason Marks and I. Glenn Cohen -- offered their perspectives on FDA’s June 2023 draft guidance proposing a framework for clinical investigations and drug development programs for psychedelic drugs (RELATED: FDA issues first psychedelic drug trial guidance, Regulatory Focus 28 June 2023).

Marks, who is an MD and a professor of law at Florida State University, is the senior fellow and project lead of the Project on Psychedelics Law and Regulation (POPLAR) at Harvard Law School, and a visiting fellow at the Information Society Project at Yale Law School. Cohen is a professor of law at Harvard Law School and the director of Harvard Law School's Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics.

The authors support FDA’s recommendation to exclude participants with pulmonary hypertension from participating in trials for classic psychedelics such as psilocybin and lysergic acid diethylamide (LSD). They also support the agency’s recommendations for follow-up echocardiography in patients receiving long-term administration of 5-HT2B agonists used in LSD and psilocybin.

However, the authors said the agency’s approach to psychotherapy for patients receiving psychedelic treatment requires greater scrutiny. Under the proposed guidance, sponsors are urged to justify the inclusion of psychological support since it may complicate the assessment of effectiveness. Stakeholders commenting on the guidance have disagreed with FDA’s approach regarding the use of psychological support (RELATED: Psychedelic drug trial guidance: Commenters see vital role for psychotherapy, Regulatory Focus 29 August 2023).

Marks and Cohen suggested that the agency is not necessarily dismissing the role of psychological support but is emphasizing the “need to rigorously study these variables.”

“If the FDA concludes that psychedelics can safely treat PTSD, addiction, or treatment-resistant depression with limited support, it could be standard practice to offer but not uniformly require psychological support after FDA approval,” Marks and Cohen wrote.

The authors took issue with FDA’s characterizing the subjective effects of psychedelics, such as hallucinations and emotional changes, as abuse-related adverse events.

“We believe characterizing subjective effects as ‘abuse related’ is unwarranted. Classic psychedelics are nonaddictive and may have nonaddictive properties, and their subjective effects could inhibit long-term consumption of psychedelics and substances such as alcohol, cocaine, and tobacco,” they wrote.

Overall, the guidance is “well-reasoned” but improvements are needed with respect to recommendations for psychological support and adverse event reporting, the authors concluded.

According to panelists speaking at RAPS Convergence 2023, psychedelic drug development is receiving more attention lately as these treatments offer the potential for needed therapeutic alternatives for various mental health conditions, yet developers need to take care in designing trials and balancing risk profiles (RELATED: Convergence: Psychedelic drug development is ‘hot,’ but proceed with caution, Regulatory Focus 4 October 2023).

FDA profiles cannabis drug development and research

In another recently published article, FDA authors discussed the agency’s outlook on cannabis research and drug development in the journal Exploration of Medicine.

Cassandra Taylor and Schuyler Pruyn discussed FDA’s criteria for evaluating investigational new drug applications (INDs) for cannabis, the pre-IND consultation program, drug master files (DMFs) and the future of cannabis drug development.

The authors noted that when INDs for cannabis-derived products (CCDPs) are submitted, the research is reviewed the same way as any other product regulated as a drug. While FDA has not yet approved a marketing drug application for cannabis, over the last 50 years, the agency has received more than 800 INDs evaluating CCDPs, including synthetic active pharmaceutical ingredients.

The authors predict that FDA will continue to see an increase in INDs evaluating CCDPs. They also note that “as more medical and adult-use (i.e., non-medical) programs at the state-level evolve, there will likely be increased interest in clinical research to study CCDPs that are commonly used by consumers in state-level programs.”

NEJM perspective, FDA study on cannabis research

Perspective: FDA moving in the right direction with psychedelic drug guidance

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