Psilocybin inhibits formalin-induced nociception through 5-hydroxytryptamine 2A receptor in rats
Saadet Inan, Paige E. Morris, Scott M. Rawls, Stephanie E. Daws
Behavioural Pharmacology September 25, 2025 DOI: 10.1097/fbp.0000000000000856 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Adult male Sprague-Dawley rats |
| Intervention | Psilocybin |
| Dose | 0.1, 0.3, and 1 mg/kg, IP |
| Duration | 6 hours after psilocybin administration, with pain behavior recorded 0-10 minutes and 20-60 minutes after formalin injection |
| Topics | Psilocybin |
| Key findings | Psilocybin reduced acute and tonic inflammatory pain behaviors in rats, an effect blocked by a 5-HT 2A receptor antagonist. |
Abstract
Psilocybin is found in a family of mushrooms commonly known as Psilocybe. We aimed to study the antinociceptive efficacy of psilocybin using formalin-induced noxious stimuli, a model that comprises both acute and persistent pain in rats. Adult male Sprague–Dawley rats were used. Psilocybin (0.1, 0.3, and 1 mg/kg, IP) or vehicle was administered, and 6 h later, formalin (5%, 50 µL, subcutaneous) was injected into the hindpaw, and the number of flinches and time spent for licking were recorded for 0–10 and 20–60 min for acute and tonic phases, respectively. Another set of rats was used to examine if the antinociceptive effect of psilocybin is via 5-hydroxytryptamine 2a receptor (5-HT 2A R). For this aim, rats were pretreated with volinanserin (0.1 mg/kg, highly selective 5-HT 2A R antagonist) or vehicle 30 min before psilocybin (0.3 mg/kg). Six hours later, formalin was injected, and the number of flinches and time spent for licking were recorded. Psilocybin (0.1 and 0.3 mg/kg) significantly reduced flinching and licking behaviors in both acute and late pain phases and pretreatment with volinanserin blocked the antinociceptive effect of psilocybin. Our results suggest that psilocybin produces an analgesic effect for acute and tonic inflammatory pain, at least in part, by activating 5-HT 2A R.
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
Cites 25
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
- Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology May 20, 2016
- Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways Current Topics in Behavioral Neurosciences 2017
- Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. Neuropharmacology May 1, 2020
- Psychedelics as anti-inflammatory agents International Review of Psychiatry July 4, 2018
and 20 more in the library