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.
JAMA psychiatry
January 1, 2023
Brian D Kiluk, Bethea A Kleykamp, Sandra D Comer et al.
22 citations
A review sponsored by a public-private partnership addresses clinical trial design for new opioid use disorder (OUD) treatments that target systems other than the μ-opioid receptor. The authors present consensus recommendations for evaluating novel therapies such as cannabinoids, psychedelics, sedative-hypnotics, and immunotherapeutics. Key design elements include specifying the treatment stage (e.g., early abstinence, long-term recovery), defining the treatment's role (adjunctive or independent), selecting patient-informed primary outcomes that assess opioid use patterns, retention, and quality of life, and monitoring adverse events like relapse or overdose, especially when patients are not on maintenance opioid agonist or antagonist medications. Incorporating input from people with lived experience is urged to accelerate development and uptake of effective therapeutics.
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.
The Journal of pharmacology and experimental therapeutics
October 18, 2024
Rachel Luba, Gabriela Madera, Rebecca Schusterman et al.
2 citations
Lenabasum, a selective CB2 receptor agonist, was tested for abuse potential in 56 people who use cannabis recreationally. At the target therapeutic dose of 20 mg, lenabasum did not increase ratings of drug liking compared with placebo. However, higher, supratherapeutic doses of 60 and 120 mg did produce dose-dependent increases in drug liking, though less than nabilone, an FDA-approved medication. Lenabasum was safe and well tolerated, but it does have abuse potential and should be used cautiously in clinical settings.