Neuropharmacology
May 27, 2023
David J. Heal, Sharon L. Smith, Sean J. Belouin et al.
50 citations
This special issue of Neuropharmacology provides a comprehensive update on basic and clinical research on psychedelics since 2018, partly based on the NIH Psilocybin Research Speaker Series held from April to June 2021. The FDA has granted breakthrough therapy designations for psilocybin in treatment-resistant depression (2018) and major depressive disorder (2019), and for MDMA in post-traumatic stress disorder (2017). Clinical trials are ongoing for psilocybin in depression, cancer-related anxiety and depression, anorexia, PTSD, substance use disorders, and chronic pain. The collection aims to support the transition of psychedelics from bench to mainstream therapies, with global implications following potential FDA approvals.
Neuropharmacology
December 15, 2022
David J. Heal, Jane Gosden, Sharon L. Smith et al.
18 citations
Classical psychedelics (psilocybin, LSD, DMT) and the entactogen MDMA are being investigated as treatments for psychiatric, neurological, and peripheral disorders. These drugs act through 5-HT2A and other serotonergic receptors or monoamine transporters. Serotonin acts as a neurotransmitter and hormone with vasoconstrictor, pro-inflammatory, and pro-nociceptive effects throughout the brain and body. While existing psychedelics and entactogens have known safety and toxicity risks assessed through human experience, novel drug-candidates require non-clinical testing to predict efficacy and address risks. The authors define challenges for developing novel serotonergic psychedelics and entactogens, describing screening techniques including a non-clinical cascade, models for hallucinogenic activity, differentiation of hallucinogens from entactogens, preclinical lead optimization technology, and modified animal models for abuse and dependence risks. The goal is to reset the benefit-harm balance for safer clinical psychedelics.
Journal of Psychopharmacology
October 16, 2025
David J. Heal, Jane Gosden, Sharon L. Smith
4 citations
Psychedelic research is advancing rapidly, creating new challenges for drug developers, regulators, and legislators. Most classic psychedelics under clinical investigation are Schedule I controlled substances with high abuse potential and no accepted medical use. These and next-generation psychedelic drug-candidates require scientific and clinical assessment of their abuse and dependence potential before being placed into a lower controlled drug schedule (C-II to C-V). The FDA is likely to conduct the first regulatory assessment of a classic psychedelic and has provided guidance on addressing clinical and regulatory challenges. This review builds on that foundation, discussing areas of abuse and dependence evaluation that remain unclear.