Intravenous psilocybin attenuates mechanical hypersensitivity in a rat model of chronic pain

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There is a renewed interest in psychedelic drugs as potential therapeutic agents for the treatment of psychiatric disorders. In particular, psilocybin has shown promise for the treatment of refractory depression1Roseman L. Nutt D.J. Carhart-Harris R.L. Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression.Front. Pharmacol. 2017; 8: 974https://doi.org/10.3389/fphar.2017.00974Crossref PubMed Scopus (353) Google Scholar and major depressive disorder2Davis A.K. Barrett F.S. May D.G. Cosimano M.P. Sepeda N.D. Johnson M.W. Finan P.H. Griffiths R.R. Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial.JAMA Psychiatry. 2021; 78: 481-489https://doi.org/10.1001/jamapsychiatry.2020.3285Crossref PubMed Scopus (473) Google Scholar, and has also been explored as a treatment for tobacco and alcohol abuse3Johnson M.W. Garcia-Romeu A. Griffiths R.R. Long-term follow-up of psilocybin-facilitated smoking cessation.Am. J. Drug Alcohol Abuse. 2017; 43: 55-60https://doi.org/10.3109/00952990.2016.1170135Crossref PubMed Scopus (316) Google Scholar,4Bogenschutz M.P. Forcehimes A.A. Pommy J.A. Wilcox C.E. Barbosa P.C. Strassman R.J. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study.J. Psychopharmacol. 2015; 29: 289-299https://doi.org/10.1177/0269881114565144Crossref PubMed Scopus (631) Google Scholar. However, despite suggestive evidence5Bornemann J. Close J.B. Spriggs M.J. Carhart-Harris R. Roseman L. Self-medication for chronic pain using classic psychedelics: a qualitative investigation to inform future research.Front. Psychiatry. 2021; 12735427https://doi.org/10.3389/fpsyt.2021.735427Crossref Scopus (9) Google Scholar,6Kooijman N.I. Willegers T. Reuser A. Mulleners W.M. Kramers C. Vissers K.C.P. van der Wal S.E.I. Are psychedelics the answer to chronic pain: A review of current literature.Pain Pract. 2023; 23: 447-458https://doi.org/10.1111/papr.13203Crossref Scopus (2) Google Scholar, there has been no systematic study to investigate the effectiveness of psilocybin in attenuating indices of chronic pain. To address this gap, we investigated the effect of psilocybin on mechanical hypersensitivity and thermal hyperalgesia in a well-established rat model of formalin-induced, centralized chronic pain7Fu K.Y. Light A.R. Maixner W. Long-lasting inflammation and long-term hyperalgesia after subcutaneous formalin injection into the rat hindpaw.J. Pain. 2001; 2: 2-11https://doi.org/10.1054/jpai.2001.9804Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar,8Vanini G. Sleep deprivation and recovery sleep prior to a noxious inflammatory insult influence characteristics and duration of pain.Sleep. 2016; 39: 133-142https://doi.org/10.5665/sleep.5334Crossref PubMed Scopus (20) Google Scholar and demonstrate that a single intravenous bolus administration of psilocybin can attenuate mechanical hypersensitivity for 28 days.