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.

doi:10.1101/2025.09.15.676273

bioRxiv · 10.1101/2025.09.15.676273

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.

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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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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. Psilocybin ameliorates neuropathic pain-like behaviour in mice and facilitates gabapentin-mediated analgesia. https://doi.org/10.1101/2025.09.15.676273

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