Considerations in assessing the abuse potential of psychedelics during drug development

The abuse potential of classic psychedelics—serotonergic 5-HT2A agonists such as psilocybin—has not been systematically assessed using modern methods since they were placed in Schedule I of the Controlled Substances Act in 1970. This paper reviews the scientific evaluation of their abuse potential and outlines the data required to support a rescheduling recommendation if a classic psychedelic drug product receives FDA approval. The authors argue that renewed clinical research necessitates revisiting these drugs' regulatory classification, given that Schedule I status assumes high abuse potential and no accepted medical use, a designation that may no longer align with current evidence.

Study at a glance

Abstract

The recent increase in clinical research on the potential therapeutic uses of classic psychedelics has prompted the need to revisit the assessment of the abuse potential of these drugs. The term "classic psychedelic" is used in this manuscript to describe serotonergic 5-HT2A agonists that alter perception, cognition, and mood (i.e., psychedelic effects) and that are currently controlled in Schedule I of the Controlled Substances Act (CSA). Schedule I drugs are subject to the most restrictive controls under the CSA, as they are considered to have a high abuse potential and no currently accepted medical use in the United States (USA). However, these classic psychedelics were placed in Schedule I at the time the CSA was enacted in 1970, and their abuse potential has not been systematically assessed using modern methodology. This paper provides an overview of scientific evaluation of the abuse potential of classic psychedelics and delineates the data that will be needed in support of a recommendation for the rescheduling, if a drug product containing a classic psychedelic gains FDA approval. This article is part of the Special Issue on 'National Institutes of Health Psilocybin Research Speaker Series'.