Psychedelic Drug Development and Patient Safety Under FDA Scrutiny at Public Hearing

On Monday, the FDA held a four-hour public hearing to gather feedback on the potential therapeutic applications of psychedelic drugs.

The majority of the 80 speakers expressed strong support for psychedelic medicine, highlighting its efficacy in treating severe mental health conditions such as major depressive disorder and post-traumatic stress disorder (PTSD). However, several participants raised concerns regarding clinical trial standardization, the need for risk evaluation and mitigation strategies (REMS), and patient safety.

Marta Sokolowska, PhD, deputy center director for substance use and behavioral health at the FDA’s Center for Drug Evaluation and Research, stated that the hearing is part of a whole-of-government effort to better understand the opportunities, challenges, and public health considerations associated with this evolving area of psychedelic drug treatment. “Most importantly, we are here today to listen,” she emphasized.

Sokolowska noted that the agency also seeks input on provider credentialing, patient safety protocols, equitable access, and data centralization.

The hearing follows recent Trump administration efforts to accelerate reviews of certain psychedelics, including ibogaine, under an executive order signed in April. Sokolowska explained, “This executive order establishes a policy to accelerate innovative research models and appropriate drug approvals, helping to increase access to psychedelic drugs for serious mental illness.”

In line with this initiative, the FDA recently awarded priority review vouchers to two companies studying psilocybin for major depressive disorder and treatment-resistant depression, as well as a third voucher for methylone—a derivative related to midomafetamine (MDMA)—for PTSD. Additionally, the FDA allowed an early-phase clinical study of noribogaine hydrochloride to proceed under an investigational new drug application for alcohol use disorder.

The meeting built on the FDA’s finalized clinical guidance for psychedelic drug developers published in July. This framework was featured in a New England Journal of Medicine commentary by four agency employees, who highlighted the difficulty of maintaining double-blind integrity in psychedelic trials.

The FDA authors wrote, “This absence of expected effects not only compromises blinding integrity but may also induce a disappointment effect, wherein participants experience negative outcomes because they believe they received an inactive treatment.”

Several speakers acknowledged this limitation on Monday and urged the agency to demonstrate flexibility.

Mark Rasenick, PhD, of the American Brain Coalition, stated that studies with psychedelics cannot be placebo-controlled to the extent of more traditional therapeutics. He added, “Expectation bias is difficult to overcome. The role of monitors and therapists is difficult to assess, and not in the traditional province of the FDA. Yet published results are exciting and can’t be ignored. There’s already evidence that psychedelics are effective therapeutics.”

Rhonda DeSantis, founder and CEO of Psylutions, asked the agency to establish clear, clinically defined endpoints so patients “receive the same reproducible medicine and the same standard of care.”

Veterans and patient advocates emphasized the stark lack of treatment options for individuals with severe conditions. Eric Jansen, a Marine Corps veteran with the Balanced Veterans Network, credited his survival to two overseas psychedelic treatments using ayahuasca and ibogaine.

“Veterans should not be forced to choose between suffering, going underground, or leaving the country just for standard care,” Jansen urged. “No veteran should need a passport to find hope.”

Safety advocates countered with calls for strict guardrails. Kevin Sabet, PhD, of the Foundation for Drug Policy Solutions, cited rising non-fatal emergency calls involving ketamine, referencing the high-profile overdose death of actor Matthew Perry.

“We need to make sure we have approval first, and then access,” Sabet said. “When considering harms, we need to look at psychosis, visual disturbances, mania, suicidal thoughts, heart problems, misuse, and therapist misconduct.”

Multiple speakers echoed concerns over practitioner misconduct, citing past instances of inappropriate sexual contact during studies, including a high-profile case involving a clinical trial investigator, and called for strict patient consent protections.

Experts also cautioned against broad, heavy-handed regulatory frameworks that may limit patient access.

Lawrence Goldkind, MD, a former FDA deputy division director, noted that not all psychedelics have similar abuse potential, and the safety profiles of the various psychedelics are not the same. He urged, “I strongly urge the FDA not to use a templated class labeling and REMS for all psychedelics. Labeling and REMS should be tailored to the specific drug based on the data.”

Goldkind warned that onerous administrative burdens could affect solo practitioners, small facilities, and rural clinics serving underinsured populations.

The FDA is accepting public comments on the docket through October 5.

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