No evidence of immediate or persistent analgesic effect from a single dose of psilocybin in three mouse models of pain
Nicholas Gregory, Tyler E. Girard, Akila Ram, Austen B Casey, Rc Malenka, Vivianne L. Tawfik, Boris D. Heifets
Nature Communications January 22, 2026 DOI: 10.1038/s41467-026-68763-z (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Male and female mice |
| Intervention | Psilocybin |
| Dose | 0.3, 2, and 10 mg/kg i.p. |
| Topics | Psilocybin |
| Keywords | Analgesic Hallucinogen Anesthesia Neuropathic pain Hypothermia Hyperalgesia Pharmacology Threshold of pain Cold sensitivity Nociception Chronic pain Drug |
| Citations | 5 |
| Key findings | Psilocybin produced no analgesic effects across multiple pain models and assays except for cold sensitivity, which was likely explained by hypothermia rather than true analgesia. |
Abstract
The psychedelic psilocybin may have lasting therapeutic effects for patients with chronic pain syndromes. Some preclinical data suggest these putative benefits derive from direct analgesic effects; however, this possibility has not been comprehensively tested in preclinical models. Here, we evaluated the analgesic properties of a single exposure to psilocybin at acute and chronic time points in Complete Freund's Adjuvant-induced inflammatory pain, spared nerve injury model of neuropathic pain, and acid-induced muscle pain. Across these models, we tested a range of doses (0.3, 2, and 10 mg/kg i.p.) in male and female mice using multiple behavioral assays evaluating sensory aspects (von Frey, cold plate, Hargreaves, thermal place preference, and muscle withdrawal threshold) and functional aspects of pain (marble burying). We further tested the effects of psilocybin on the affective dimension of pain in a surgical model of acute pain (mouse grimace scale). Except for cold sensitivity, we found no effect of psilocybin across pain models, behavioral assays, drug doses, or sex. The apparent reduction in cold sensitivity may be explained by profound hypothermia induced by psilocybin rather than true analgesia.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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 |
Citations in the library
Cited by 6
- Current status and future prospects of research on psilocybin's regulation of neurotransmitters and their receptors related to the pathogenesis of tinnitus. Hearing research August 1, 2026
- Classic Psychedelics for Treating Chronic Pain: Mechanism and Clinical Translation Molecules July 27, 2026
- Classic Psychedelics for Chronic Pain: A Critical Review of the Literature and Practical Advice for Clinicians. Drugs June 4, 2026
- LSD persistently disrupts affective pain processing. bioRxiv : the preprint server for biology May 11, 2026
- Psilocybin and Chronic Neuropathic and Centralized Pain: Converging Mechanisms in Central Sensitization, Neuroplasticity, and Network Organization Anesthesia Research September 11, 2026
and 1 more in the library
Cites 32
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder JAMA Psychiatry August 24, 2022
and 27 more in the library