Developing Psychedelics into Medicines: Potential Opportunities and Pitfalls

Categories: FDA, Psychedelics, Risk Management, Scheduling

By Daniel Wang

Psychedelics, a class of powerful psychoactive substances that alter perception and cognition, have for decades been relegated to the dark corners of illicit recreational substances after many of them were placed in Schedule I of the 1970 Controlled Substances Act (CSA).

However, the Food and Drug Administration (FDA) signaled that the Agency sees therapeutic promise in these substances when it granted Breakthrough Therapy designation to midomafetamine containing 3,4-Methylenedioxymethamphetamine (commonly known as MDMA or ecstasy) in 2017 and a psilocybin therapy for treatment-resistant depression  in 2018.  In doing so, the FDA opened up potential opportunities that have historically been non gratae.

Medicinal use of psychedelics dates back thousands of years, but became more mainstream with the synthesis of lysergic acid diethylamide (LSD) in the 1930s, and its widespread distribution among medical researchers by Sandoz Inc in the 50s and 60s. However, reports of disastrous consequences such as accidents, suicides, murders, and other criminal acts linked to use of LSD, along with the drug’s association with 1970s counterculture, contributed to psychedelics losing favor within the political and medical communities and their subsequent placement into Schedule I of the CSA.

As a Schedule I substance, sales, possession, and research into a drug’s uses are restricted to individuals and institutions who meet strict criteria for licensing imposed by the Drug Enforcement Administration (DEA). Practically speaking, the result is a severe constraint on research into the potential benefits and other effects of these substances.  Yet over the past 20 years, research out of major universities such as the Johns Hopkins University and Imperial College London points towards the potential for psychedelics to treat anxiety, depression, and substance use disorders with effects that last longer and feature fewer side effects than widely accepted mainstream treatments.

Internationally recognized leading clinical and abuse potential experts, PinneyAssociates’ Sid Schnoll, MD, PhD and Jack Henningfield, PhD and RenaSci’s David Heal, PhD, described the unique challenges in developing psychedelics into medicines and how to address them throughout the development process during a complimentary webinar available here >> webinar.

“Understanding the traditional uses of psychedelics and management of their effects can inform current drug development plans,” observed Dr. Schnoll.

“Statements by the Controlled Substances Staff (CSS) of FDA together with the Schedule V classification of Epidiolex suggest that the CSS will approach psychedelics much like any other CNS drug candidate when it comes to controlled drug status and scheduling,” said Dr. Heal. He outlined the steps necessary to assess abuse potential in preclinical trials, including types of studies required, how to evaluate results in the context of psychedelics, and the specific technical challenges when evaluating psychedelics as compared to other drugs of abuse.

Urging drug developers to use evidence obtained during the drug development process to inform postmarketing plans, Dr. Henningfield emphasized that “commitment to a strong Risk Evaluation and Mitigation Strategy (REMS) to address likely abuse-related issues is vital in approval of studies, fundraising, alleviating social and political concerns, and to ensure patient safety.”