Early psilocybin intervention alleviates behavioral despair and cognitive impairment in stressed Wistar rats
Zitong Wang, Brett Robbins, Ryan Zhuang, Thaisa Sandini, Rebekah van Bruggen, Xin-Min Li, Yanbo Zhang
Progress in Neuro-Psychopharmacology and Biological Psychiatry 2025 DOI: 10.1016/j.pnpbp.2024.111243 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experiment Peer reviewed |
|---|---|
| Sample size | 22 |
| Population | Male Wistar rats |
| Intervention | Psilocybin |
| Topics | Psilocybin |
| Keywords | Psilocybin magic mushrooms Psychedelics Hallucinogens Stress hormones Stress management Endocannabinoid system ecs Chronic stress Hypothalamic-pituitary-adrenal hpa axis |
| Citations | 15 |
| Key findings | Psilocybin reduced stress-induced behavioral despair and cognitive impairments, likely through endocannabinoid-mediated downregulation of the HPA axis. |
Abstract
Chronic stress exerts profound effects on mental health, contributing to disorders such as depression, anxiety, and cognitive impairment. This study examines the potential of psilocybin to alleviate behavioral despair and cognitive deficits in a rodent model of chronic stress, focusing on the interplay between the Hypothalamic-Pituitary-Adrenal (HPA) axis and the Endocannabinoid System (ECS). Twenty-two male Wistar rats were divided into control and stress groups. Animals within the stress group were exposed to predator odor and chronic social instability to induce chronic stress, and were either sham treated, or given psilocybin. Behavioral assessments were conducted using the Open Field Test, Sucrose Preference Test, Novel Object Recognition, Elevated Plus Maze, and Forced Swimming Test to evaluate locomotion, anhedonia, memory, anxiety, and behavioral despair, respectively. Blood and brain samples were analyzed for biochemical markers. Results indicated that psilocybin significantly reduced stress-induced behavioral despair and cognitive impairments, likely through ECS-mediated downregulation of the HPA axis. These findings suggest that early intervention with psilocybin has sustained beneficial effects on stress-related behavioral and cognitive disturbances, underscoring its potential as a novel therapeutic approach for stress-related mental health disorders.
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 15
- Psilocybin mitigates behavioral despair and cognitive impairment in treatment-resistant depression model using wistar kyoto rats. Scientific Reports May 26, 2025
- An exploration of the relationships between the effects of psilocybin on behavior, 5-HT 2A receptor occupancy, and neuroplastic effects in mice Journal of Psychopharmacology January 6, 2026
- Psilocybin as a fast-acting and long-lasting antidepressant for adolescence: Proposing NeuroD1 as a biomarker of its long-term plasticity Biomedicine & Pharmacotherapy October 30, 2025
- Endocannabinoids, depression, and treatment resistance: Perspectives on effective therapeutic interventions Psychiatry Research August 18, 2025
- Psilocybin for Anhedonia in Unipolar and Bipolar Depression: A Systematic Review of Clinical and Preclinical Evidence Journal of Psychiatric Research October 1, 2026
and 10 more in the library
Cites 35
- 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
- Patients’ Accounts of Increased “Connectedness” and “Acceptance” After Psilocybin for Treatment-Resistant Depression Journal of Humanistic Psychology June 19, 2017
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
and 30 more in the library