Neuropharmacology
August 17, 2022
Jack E Henningfield, Marion A Coe, Roland R Griffiths et al.
34 citations
New medicines containing classic hallucinogenic and entactogenic psychedelics like psilocybin, LSD, and MDMA are being developed for psychiatric and neurological disorders. These substances are currently Schedule I under the US Controlled Substances Act (CSA) and similarly controlled globally. The CSA framework governs research, drug approval, and rescheduling; upon FDA approval, a drug containing a Schedule I substance must be rescheduled. Abuse potential research informs the eight CSA factors used for rescheduling, as well as product labeling and required risk evaluation and mitigation strategies (REMS). Standard human abuse potential studies are problematic for strong hallucinogens like psilocybin, so alternative strategies are discussed. Abuse-related research may also illuminate mechanisms of action, therapeutic effects, and effects on brain, behavior, mood, spirituality, and consciousness.
Journal of Psychopharmacology
January 1, 2023
Jack E Henningfield, Judy Ashworth, David J Heal et al.
13 citations
Psychedelics present unique challenges for abuse potential assessment due to their distinct pharmacological profiles: entactogens act as weak reinforcers and hallucinogens as non-reinforcers, requiring more flexible approaches than standard regulatory guidelines. Standard nonclinical techniques like receptor binding and physical dependence tests adapt easily, while human abuse trials need modification because supratherapeutic doses may be unsafe and safety monitoring procedures can bias outcomes. Existing knowledge varies widely, from extensive data on psilocybin to none for novel compounds. Many assessments can be applied to animals and humans without compromising scientific integrity, but human abuse studies merit reconsideration to ensure safety and validity. Other methods can evaluate pharmacological equivalence to known drugs of abuse to guide scheduling.
Journal of psychopharmacology (Oxford, England)
January 1, 2026
Jack E Henningfield, Sandra D Comer, Matthew L Banks et al.
5 citations
A panel of abuse potential experts convened to discuss challenges in assessing the abuse potential of novel drugs, especially psychedelics and cannabinoids. The U.S. Controlled Substances Act scheduling process, intended to balance public safety with medicinal access, can be overly restrictive when abuse potential is overestimated, as postmarketing evaluations have suggested for some substances. Existing methods recommended by the FDA are generally reliable for many drug categories but require modifications—such as behavioral economic assessments and broader outcome measures in human abuse potential studies—to accurately characterize newer agents. The commentary emphasizes the need for updated approaches to ensure valid scheduling decisions that protect public health without hindering access to beneficial medicines.
Journal of psychopharmacology (Oxford, England)
December 1, 2025
David J Heal, Sharon L Smith, Jack E Henningfield
1 citation
This special issue of the Journal of Psychopharmacology honors Roland R. Griffiths, whose pioneering work in psychedelic research helped revive the field globally. It opens with a tribute from colleagues summarizing his contributions to neuropharmacology, psychiatry, and the therapeutic effects of psychedelics. The issue includes commentaries, reviews, and original research organized into non-clinical, clinical, and strategic/regulatory sections. Contributions from international experts provide a comprehensive resource on the current state of psychedelic research.