Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

Neuropsychiatric disorders

‘Magic’ mechanisms underlie psilocybin’s effects in chronic pain

Nature Reviews Neuroscience volume 27, page 3 (2026)Cite this article

Subjects

Although mood dysfunctions (such as anxiety and depression) are common comorbidities in people with chronic pain conditions, therapeutic options that tackle both pain and mood are limited. In a new study, Hammo et al. show that, in mouse models of pain that include depression-like behaviours, a single dose of psilocybin (the psychoactive compound found in ‘magic mushrooms’) rapidly attenuates these behaviours in a sustained fashion.

Emerging evidence suggests that psilocybin is efficacious in managing pain conditions. Here, the authors examined its effects in models of inflammatory and neuropathic pain states: injection of Freund’s complete adjuvant (CFA) into the hindpaw and spared nerve injury of the sciatic nerve (SNI), respectively, combined with behavioural tests of anxiety-like effects (elevated plus maze) and depression-like effects (forced swim test). Both CFA and SNI resulted in mechanical hypersensitivity that stabilized after around 4 weeks and was accompanied by an increase in depression- and anxiety-like behaviours. Administration of a single dose of psilocybin intraperitoneally 27 days after the insult rapidly reversed mechanical hypersensitivity in male and female mice, and this effect persisted for the duration of monitoring (12 days after administration). Remarkably, this treatment also substantially normalized the increased anxiety- and depression-like behaviours in these mice.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

References

Original article

Download references

Author information

Authors and Affiliations

  1. Nature Reviews Neuroscience http://www.nature.com/nrn/

    Sian Lewis

Authors
  1. Sian Lewis
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Sian Lewis.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lewis, S. ‘Magic’ mechanisms underlie psilocybin’s effects in chronic pain. Nat. Rev. Neurosci. 27, 3 (2026). https://doi.org/10.1038/s41583-025-00999-y

Download citation

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41583-025-00999-y

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing