Psilocybin has no immediate or persistent analgesic effect in acute and chronic mouse pain models

Authors
Nicholas S Gregory, Tyler E Girard, Akila Ram, Austen B Casey, Robert C Malenka, Vivianne L Tawfik, Boris D Heifets


Lab

Journal
bioRxiv

Abstract
Our findings contradict recent pre-clinical studies testing various serotonergic psychedelics in other pain models. Kolbmann et al. showed that i.v. administration of psilocin produced immediate and persistent reductions in mechanical and thermal hyperalgesia induced by formalin in rats16. This discrepancy may be explained by differences in the route of drug administration or the species used51. Lauria et al. found ayahuasca--an herbal brew most commonly made with material fromB. caapiandP. viridisplants containing a range of psychoactive substances, includingN,N-dimethyltriptamine (DMT) and multiple harmala alkaloids that act on the 5-HT2AR--had acute (on-drug) analgesic effects in inflammatory and neuropathic pain models, however, consistent with our findings, no analgesic effects were observed at later time points18,52. These plants also contain monoamine oxidase inhibitors, which alter the metabolism of DMT as well as endogenous monoamines52. A recent preprint reports that psilocybin (both 0.3 mg/kg and 1 mg/kg) very modestly (i.e. visible with log-transformation) improved SNI-induced mechanical sensitivity for days to weeks after a single dose. 0.3 mg/kg psilocybin reduced cold sensitivity over a similar time course, but 1 mg/kg psilocybin appeared less effective. The small effect size and inconsistent dose relationship have uncertain biological relevance19. Overall, preclinical studies from other groups have not consistently demonstrated post-acute analgesic effects of serotonergic psychedelics, and methodological differences or hypothermic effects may potentially explain differences observed at acute time points.

Keywords/Topics
pain;psychosis

BIOSEB Instruments Used:
Rodent pincher - Analgesia meter - Wireless (BIO-RP-WRS)

Source :

https://pmc.ncbi.nlm.nih.gov/articles/PMC12265607/

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