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Psilocybin ameliorates neuropathic pain-like behaviour in mice and facilitates gabapentin-mediated analgesia

Askey, T.; Allen-Ross, D.; Luzyanin, D.; Lasrado, R.; Gilmour, G.; Hunt, S. P.; Tamagnini, F.; Ahmed, M.; Stephens, G. J.; Maiaru, M.

2025-09-17 neuroscience
10.1101/2025.09.15.676273 bioRxiv
Show abstract

Chronic pain states are challenging to control with current drug therapies. Here, we demonstrate that a single dose of psilocybin can produce a sustained anti-nociceptive effect in a model of chronic neuropathic pain in male and female mice. Psilocybin anti-nociceptive effects were mediated by 5-HT2A receptors, although additional mechanisms might also be involved. Furthermore, a single dose of psilocybin caused a significant increase in the anti-nociceptive potential of gabapentin, a widely used treatment for neuropathic pain consistent with the establishment of longer lasting changes in network processing. Overall, these findings present the first preclinical evidence that psilocybin could be a valuable approach for treating chronic pain from nerve injury and serve as a new therapeutic addition for pain management.

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