Neuropharmacology
June 5, 2018
Matthew W. Johnson, Roland R. Griffiths, Peter S. Hendricks et al.
348 citations
Psilocybin, like other classic psychedelics that activate 5-HT2A receptors, has limited reinforcing effects and only marginal, transient non-human self-administration, indicating low abuse potential. Illicit use of psilocybin-containing mushrooms is occasional, with a few lifetime uses being typical. Potential harms include dangerous behavior in unprepared, unsupervised users and exacerbation of mental illness in those predisposed to psychotic disorders, but the scope of use and associated harms are low compared to prototypical abused drugs. The medical model mitigates these risks through dose control, patient screening, preparation, follow-up, and session supervision. If approved as a medicine, the review suggests that Schedule IV placement under the US Controlled Substances Act may be appropriate.
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
August 13, 2022
Ingrid Donato, Veronica Magar, Sean J Belouin et al.
49 citations
Psychedelic and entactogen medicines like psilocybin and MDMA, when combined with psychosocial support, show potential for safe, rapid, and durable clinical improvements. Both have received Breakthrough Therapy designation from the US FDA and may gain full approval, with similar regulatory steps in other countries. Regulatory changes are also increasing access to legal or decriminalized psychedelic use outside medical settings. This review covers historical use, current evidence, and policy considerations around standards of practice, consumer protection, community engagement, equitable access, and data standards. It suggests a public-private partnership involving diverse stakeholders to co-create best practices and public policies supporting responsible, ethical use.
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.
Neuropharmacology
April 2, 2023
Farah Z Zia, Michael H. Baumann, Sean J Belouin et al.
28 citations
Chronic pain is a leading cause of disability and opioid overdose in the United States. While many people manage pain with existing medicines and psychosocial treatments, others find these options ineffective or unacceptable due to side effects and risks. Preliminary evidence suggests psychedelics may improve quality of life, functionality, and reduce disability and distress for people whose pain may never be completely relieved. This commentary calls for more basic research and clinical trials to explore psychedelics' potential in chronic pain management, and to determine whether effects stem from direct antinociceptive or anti-inflammatory mechanisms, or from increased tolerability, acceptance, and spirituality that mediate therapeutic effects seen in psychiatric disorders.
Journal of Psychoactive Drugs
January 1, 2023
Julian Urrutia, Brian T Anderson, Sean J Belouin et al.
21 citations
Combining psychedelic science, contemplative practices, and Indigenous and other traditional knowledge systems in integrative, community-based models of care could transform global health. Both contemplative practices and certain psychedelic substances reliably induce self-transcendent experiences that positively affect health, well-being, and prosocial behavior, and combining them appears synergistic. Traditional knowledge systems offer ethnobotanical expertise and time-tested practices. A decolonized agenda for psychedelic research requires collaborative engagement with traditional knowledge stewards to co-develop evidence-based integrative care accessible to their communities. Health systems could include Indigenous and traditional healers as stakeholders in designing, implementing, and evaluating community-based approaches for safely scaling psychedelic treatments.
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.
Gen Psychiatr
February 19, 2025
Jérémie Richard, Albert Garcia‐romeu, Jack E Henningfield
7 citations
The FDA's August 2024 decision that an additional phase III study is needed before considering approval of midomafetamine for PTSD may postpone the potential approval of this treatment by several years.
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 (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)
January 30, 2026
Veronica Magar, Marlena Robbins, Óscar Martín López Fernández Lobo Blanco et al.
1 citation
Indigenous Peoples have long stewarded natural psychoactive medicines through ceremony and kinship, yet their contributions are often marginalized in psychedelic science. This commentary argues for reciprocal collaboration grounded in Indigenous sovereignty, cultural rights, and governance. Drawing on traditions involving ayahuasca, psilocybin, peyote, and iboga, it illustrates how Indigenous methodologies offer critical insights for safety and efficacy. The authors call for embedding free, prior, and informed consent, equitable benefit-sharing, and Indigenous leadership in research and policy, moving beyond tokenism toward systemic change. They conclude by urging formal, transparent convening processes modeled on WHO global consultations to bring Indigenous leaders, researchers, and policymakers together.
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.
Journal of psychopharmacology (Oxford, England)
January 1, 2026
Jack E Henningfield, Frederick S. Barrett, Suzette M Evans et al.
Roland R. Griffiths was a highly influential scientist in behavioral and neuropsychopharmacology, known for his rigorous research on abuse liability of substances including alcohol, benzodiazepines, caffeine, tobacco, and psychedelics. This review, authored by his former mentees and collaborators, describes his methodical approach to research, his inclusive and collegial mentoring style, and his role in advancing scientific methods for abuse liability assessment, policy, and regulation. His work culminated in the establishment of the Johns Hopkins Center for Psychedelic and Consciousness Research, reflecting his curiosity-driven, humanity-serving science that continues to inspire innovation.