Psilocybin as a lead candidate molecule in preclinical therapeutic studies of psychiatric disorders: A systematic review
James J Gattuso, Carey Wilson, Anthony J. Hannan, Thibault Renoir
Journal of Neurochemistry November 29, 2023 DOI: 10.1111/jnc.16017 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Preclinical rodent models |
| Topics | Psilocybin |
| Keywords | Animal models Psychiatric disorders Psilocybin research Psychiatric treatment Psychedelic medicine Neuroscience studies Mental health therapy |
| Citations | 18 |
| Key findings | Psilocybin shows the most efficacy for depression among neuropsychiatric conditions in preclinical rodent models, with potential therapeutic mechanisms involving altered brain connectivity. |
Abstract
Abstract Psilocybin is the main psychoactive compound found in hallucinogenic/magic mushrooms and can bind to both serotonergic and tropomyosin receptor kinase b (TrkB) receptors. Psilocybin has begun to show efficacy for a range of neuropsychiatric conditions, including treatment‐resistant depression and anxiety disorders; however, neurobiological mechanisms are still being elucidated. Clinical research has found that psilocybin can alter functional connectivity patterns in human brains, which is often associated with therapeutic outcomes. However, preclinical research affords the opportunity to assess the potential cellular mechanisms by which psilocybin may exert its therapeutic effects. Preclinical rodent models can also facilitate a more tightly controlled experimental context and minimise placebo effects. Furthermore, where there is a rationale, preclinical researchers can investigate psilocybin administration in neuropsychiatric conditions that have not yet been researched clinically. As a result, we have systematically reviewed the knowledge base, identifying 82 preclinical studies which were screened based on specific criteria. This resulted in the exclusion of 44 articles, with 34 articles being included in the main review and another 2 articles included as Supporting Information materials. We found that psilocybin shows promise as a lead candidate molecule for treating a variety of neuropsychiatric conditions, albeit showing the most efficacy for depression. We discuss the experimental findings, and identify possible mechanisms whereby psilocybin could invoke therapeutic changes. Furthermore, we critically evaluate the between‐study heterogeneity and possible future research avenues. Our review suggests that preclinical rodent models can provide valid and translatable tools for researching novel psilocybin‐induced molecular and cellular mechanisms, and therapeutic outcomes. image
Comparable studies
Other systematic reviews and meta-analyses on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Patients with cancer- or illness-related anxiety and depression, major depressive... | 2020 | Systematic review | n = 188 |
| Blinding and expectancy confounds in psychedelic randomized controlled trials | 2021 | Systematic review | |
| Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years Patients from included clinical trials | 2016 | Systematic review | |
| The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis People with elevated symptoms of anxiety and depression | 2020 | Meta-analysis | n = 117 |
| Default Mode Network Modulation by Psychedelics: A Systematic Review Participants from included studies | 2022 | Systematic review |
Citations in the library
Cited by 20
- Psilocybin increases emotional empathy in patients with major depression. Molecular Psychiatry June 1, 2025
- Mice lacking the serotonin transporter do not respond to the behavioural effects of psilocybin. European Journal of Pharmacology March 15, 2025
- Mapping psilocybin therapy: A systematic review of therapeutic frameworks, adaptations, and standardization across contemporary clinical trials Journal of Affective Disorders July 18, 2025
- Extraction Yields of Psilocybin and Psilocin: A Short Review of Current Methods and Their Implications Pharmaceuticals March 7, 2025
- Psilocybin reduces grooming in the SAPAP3 knockout mouse model of compulsive behaviour. Neuropharmacology 2025
and 15 more in the library
Cites 129
- 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
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
and 124 more in the library