Neurobiology of psilocybin: a comprehensive overview and comparative analysis of experimental models
Dotun Adeleye Adeyinka, Donelson R. Forsyth, Suzanne Currie, Nicoletta Faraone
Frontiers in Systems Neuroscience August 5, 2025 DOI: 10.3389/fnsys.2025.1585367 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Psilocybin |
| Keywords | Cognitive science Hallucinogen |
| Citations | 7 |
| Key findings | Psilocybin may promote neuroprotection, neurogenesis, and neuroplasticity, offering potential to treat neurodegenerative disorders with low risk for addiction and adverse effects. |
Abstract
Psilocybin, a compound found in Psilocybe mushrooms, is emerging as a promising treatment for neurodegenerative and psychiatric disorders, including major depressive disorder. Its potential therapeutic effects stem from promoting neuroprotection, neurogenesis, and neuroplasticity, key factors in brain health. Psilocybin could help combat mild neurodegeneration by increasing synaptic density and supporting neuronal growth. With low risk for addiction and adverse effects, it presents a safe option for long-term use, setting it apart from traditional treatments. Despite their relatively simpler neuronal networks, studies using animal models, such as Drosophila and fish, have provided essential insights on the efficacy and mechanism of action of psilocybin. These models provide foundational information that guides more focused investigations, facilitating high-throughput screening, enabling researchers to quickly explore the compound’s effects on neural development, behavior, and underlying genetic pathways. While mammalian models are indispensable for comprehensive studies on psilocybin’s pharmacokinetics and its nuanced interactions within the complex nervous systems, small non-mammalian models remain valuable for identifying promising targets and mechanisms at early research stages. Together, these animal systems offer a complementary approach to drive rapid hypothesis generation to refine our understanding of psilocybin as a candidate for not only halting but potentially reversing neurodegenerative processes. This integrative strategy highlights the transformative potential of psilocybin in addressing neurodegenerative disorders, leveraging both small and mammalian models to achieve translational research success.
Comparable studies
Other narrative reviews on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| The pharmacology of psilocybin | 2002 | Review | |
| Serotonin research: contributions to understanding psychoses | 2008 | Review | |
| Psychedelics, Meditation, and Self-Consciousness | 2018 | Review | |
| The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act | 2018 | Review |
Citations in the library
Cited by 7
- Hormonal Influences on Psilocybin Responsivity Across the Female Lifespan: Toward Personalized Psychedelic-Assisted Therapy Psychoactives November 2, 2025
- Psilocybin-induced behavioral and cellular effects. Journal of neurogenetics July 12, 2026
- Usos recreativos, medicinales y etnobotánicos de hongos alucinógenos: una revisión Multidisciplinary Collaborative Journal July 1, 2026
- DESI-MSI-Based Multi-Organ Distribution Mapping of Psilocin in Zebrafish Molecules June 18, 2026
- Psilocybin and Mental Health Outcomes: Scoping Review with ☸SAIMSARA SAIMSARA Journal June 15, 2026
and 2 more in the library
Cites 71
- 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
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
and 66 more in the library