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
September 17, 2025 preprint DOI: 10.1101/2025.09.15.676273 via OpenAlex
Summary
AI-generated from the abstractA single dose of psilocybin produced a sustained anti-nociceptive effect in a mouse model of chronic neuropathic pain, in both male and female mice. This effect was mediated by 5-HT2A receptors, though other mechanisms may also contribute. Psilocybin also significantly increased the anti-nociceptive potential of gabapentin, a common neuropathic pain treatment, suggesting longer-lasting changes in network processing. These findings provide 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.
Study at a glance
| Characteristics | Preclinical study |
|---|---|
| Population | Male and female mice with chronic neuropathic pain |
| Interventions | Psilocybin Gabapentin |
| Dose | a single dose |
| Key finding | A single dose of psilocybin produced sustained anti-nociceptive effects in a mouse model of chronic neuropathic pain and enhanced the effect of gabapentin. |
Abstract
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-HT 2A 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.