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. ORCID: https://orcid.org/0000-0001-9453-5505, Tamagnini, F. ORCID: https://orcid.org/0000-0002-8741-5094, Ahmed, M., Stephens, G. J. ORCID: https://orcid.org/0000-0002-8966-4238 and Maiaru, M. ORCID: https://orcid.org/0000-0003-0927-6567 (2026) Psilocybin ameliorates neuropathic pain-like behaviour in mice and facilitates gabapentin-mediated analgesia. Communications Biology. ISSN 2399-3642 doi: 10.1038/s42003-026-10065-7 (In Press)

Abstract/Summary

Abstract Chronic pain states remain challenging to control with current drug therapies. Here, we demonstrate that a single dose of psilocybin produces a sustained anti-nociceptive effect in chronic neuropathic pain models in male and female mice, mediated primarily by 5-HT 2A receptors. Critically, psilocybin significantly potentiates the analgesic efficacy of gabapentin, a standard-of-care treatment, representing the first preclinical evidence that a psychedelic can serve as a pain-network primer for existing analgesics. This finding represents a novel therapeutic strategy with potential clinical application, particularly for the 30-50% of neuropathic pain patients who fail gabapentin monotherapy. Our data demonstrate that a single psilocybin injection produces sustained month-long changes that enhance gabapentin efficacy in a preclinical model of human pain. Together, these findings indicate that psilocybin both acutely enhances analgesia and induces lasting changes that amplify gabapentin efficacy weeks later. Such a translation is notable in chronic pain management, where most analgesics require chronic dosing and lose efficacy through tolerance. These findings establish psilocybin as a potential therapeutic addition for pain management by enabling longer-lasting changes in pain-processing networks and enhancing the utility of established treatments.

Item Type	Article
URI	https://centaur.reading.ac.uk/id/eprint/129769
Identification Number/DOI	10.1038/s42003-026-10065-7
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Pain Research Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
Publisher	Nature Research
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