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

Tatum Askey; Daniel Allen-Ross; Daniil Luzyanin; Reena Lasrado; Gary Gilmour; Stephen P. Hunt; Francesco Tamagnini; Maqsood Ahmed; Gary J. Stephens; Maria Maiarù

doi:10.1038/s42003-026-10065-7

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

Tatum Askey, Daniel Allen-Ross, Daniil Luzyanin, Reena Lasrado, Gary Gilmour, Stephen P. Hunt, Francesco Tamagnini, Maqsood Ahmed, Gary J. Stephens, Maria Maiarù

Communications Biology April 24, 2026 DOI: 10.1038/s42003-026-10065-7 (opens in new tab)

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Study at a glance

AI-extracted from the abstract

Characteristics	Preclinical study Peer reviewed
Population	Male and female mice with chronic neuropathic pain
Interventions	Psilocybin Gabapentin
Dose	single dose
Duration	Month-long changes
Topics	Psilocybin
Key points	A single dose of psilocybin produces sustained anti-nociceptive effects and potentiates gabapentin's analgesic efficacy in mouse models of chronic neuropathic pain.

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-HT2A 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.

Comparable studies

Other preclinical and animal studies on psilocybin, most cited first.

Study	Year	Design
Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice	2021	Observational cohort
Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice	2021	Experimental study
Psychedelics reopen the social reward learning critical period Mice	2023	Experimental study in mice
Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice	2020	Experimental study with dose-response experiments
Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice	2013	Experimental study

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