Effects of psilocybin and chronic mild stress on microglial activation in rat spinal cord: an ex vivo analysis
Piotr Olejnik, Katarzyna Kamińska, Krystyna Gołembiowska, Kaja Kasarełło
Pharmacological Reports January 20, 2026 DOI: 10.1007/s43440-026-00824-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Sample size | 28 |
| Population | Adult male Wistar Han rats |
| Intervention | Psilocybin |
| Dose | 0.6 mg/kg ip |
| Duration | Two injections at 7-day intervals, spinal cords collected 1 week after the second dose |
| Topics | Psilocybin Serotonin |
| Keywords | Spinal cord Pharmacology Central nervous system Saline Hallucinogen Ex vivo Microglia Endocrinology Analgesic Cytokine Immune system Anesthesia Hyperalgesia Neuroinflammation |
| Key findings | Chronic mild stress activates microglia and immune responses in the spinal cord despite psilocybin administration, as indicated by increased Arg1, TNF-α, and IL-10 levels. |
Abstract
Introduction: Psilocybin, a classic serotonergic psychedelic, has antidepressant, anxiolytic, anti-inflammatory, and analgesic properties. However, the immunomodulatory effects of psilocybin within the central nervous system, particularly on microglial activation, remain poorly understood. Therefore, this study aimed to investigate the effects of psilocybin on microglial activation markers and cytokine levels in the spinal cord isolated from rats subjected to chronic mild stress (CMS).
Methods: Tissues were isolated from four groups of adult male Wistar Han rats, each consisting of seven animals: not subjected to CMS (control), receiving two injections of saline (0.9% NaCl ip) or psilocybin (0.6 mg/kg ip) at 7-day intervals, and subjected to CMS, receiving two injections of NaCl (0.9% NaCl ip) or psilocybin (0.6 mg/kg ip) at 7-day intervals. Spinal cords were collected 1 week after the second dose of saline/psilocybin from the sacrificed rats and stored at -80 °C. The levels of microglial activation markers (iNOS and Arg1) and pro- and anti-inflammatory cytokines (TNF-α and IL-10) were analyzed using an enzyme-linked immunosorbent assay.
Results: The spinal cords isolated from CMS rats treated with psilocybin revealed significantly increased levels of Arg1 (p = 0.0306), TNF-α (p = 0.0357), and IL-10 (p = 0. 0081) compared to tissues from control rats administered with psilocybin. Additionally, although not statistically significant, iNOS levels showed an increasing trend in CMS rats treated with psilocybin compared to those in psilocybin-receiving controls (p = 0.0755).
Conclusions: CMS activates the immune system/microglia non-specifically despite psilocybin administration. CLINICAL TRIAL NUMBER: Not applicable.
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 20
- 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
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Psychedelics as anti-inflammatory agents International Review of Psychiatry July 4, 2018
- Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression ACS Chemical Neuroscience March 5, 2020
- Psilocybin: from ancient magic to modern medicine The Journal of Antibiotics May 12, 2020
and 15 more in the library