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
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.
Neuropharmacology
August 23, 2018
David J Heal, Jack E Henningfield, Bruno G. Frenguelli et al.
7 citations
Psychedelic compounds can temporarily alter brain connectivity, potentially re-opening periods of heightened plasticity that allow rigid neural patterns to be reshaped. This process may facilitate cognitive shifts, including new perspectives and changes in emotional processing, which could underlie therapeutic breakthroughs for various mental health conditions. The text suggests that by disrupting entrenched brain networks, psychedelics enable a reconfiguration of neural pathways, offering a mechanism for lasting improvements in mental well-being.
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.
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.
Frontiers in Psychiatry
January 1, 2024
David J Heal, Jane Gosden, Sharon L. Smith
Cannabis has moderate levels of abuse and dependence risk, substantially lower than those of many illegal and legal substances like tobacco and alcohol, but far from negligible. Delta-9 tetrahydrocannabinol (Δ9-THC) and other psychoactive cannabinoids have moderate reinforcing effects, rapidly induce pharmacological tolerance, and produce a withdrawal syndrome of moderate severity lasting 2 to 6 days. Non-psychoactive cannabinoids do not produce intoxicating, cognitive, or rewarding properties in humans. Most evidence shows cannabidiol (CBD) does not attenuate the central nervous system effects of Δ9-THC, though uncertainty warrants further research. Potent synthetic cannabinoid receptor agonists pose substantial risk for abuse and harm.