Comparing psilocybin to metformin as neuroprotective agents against Parkinson's dementia: A systematic review of evidence and efficacy.
Randall D Ordovich-Clarkson, Maurice Jabbour, Daniel Arteaga Pelayo, Daniel Lara, Sebastian La Croix, Macie Mumman, Shoshanah Stukas, Reagan Anderson, David Meraz, Anthony Bangura, Brooklyn Anderson, Luke Bamrud, Caleb Blake
Progress in Neuro-Psychopharmacology and Biological Psychiatry January 10, 2025 DOI: 10.1016/j.pnpbp.2024.111155 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Cell and animal models |
| Interventions | Metformin Psilocybin |
| Topics | Psilocybin |
| Keywords | Neurodegenerative disorders neurodegeneration Brain disease Neural degeneration Neuroprotection brain protection Neural preservation Medication Preventive medicine prophylaxis Preventative Metformin Neurodegenerative disease Parkinson's disease Prophylactic treatment |
| Citations | 7 |
| Key findings | Metformin and psilocybin show potential neuroprotective and neuroplastic effects against Parkinson's disease through distinct mechanisms. |
Abstract
Treatment of Parkinson's disease (PD) has remained largely unchanged and focuses primarily on symptomatic relief through activation of dopaminergic pathways. Currently, there are no proven prophylactic approaches to the prevention of PD. This systematic review seeks to compare two separate compounds, metformin (MTF) and psilocybin, as potential prophylactic therapeutics against the development of PD. The authors conducted a systematic review focusing on primary studies that test these compounds on cell and animal models to determine if they might have any neuroprotective or neuroplastic effects. The results of this review found that MTF may halt the progression of diseases such as PD through multiple mechanisms including reduced oxidative stress at the level of the mitochondria, thereby reducing α-synuclein related damage. Psilocybin, on the other hand, may increase repair of damaged neurons through psychoplastogenic activation of serotonergic pathways, particularly 5-HT2A receptor activation, ultimately increasing the release of brain derived neurotropic factor (BDNF) and the reduction of α-synuclein accumulation. Implications of this study include a need for further research in off-label use of MTF as well as further research into serotonergic compounds such as psilocybin for the treatment and prevention of neurodegenerative diseases.
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 5
- Psychedelics in the Treatment of Neurologic and Psychiatric Disorders: Coincidence or a New Point of View. Molecular Neurobiology June 4, 2025
- Psychedelics and the Serotonin Hypothesis of Eating Disorders Brain Sciences August 21, 2025
- Psilocybin’s kinematic effect on manual dexterity Psychopharmacology June 17, 2026
- Priorities for psychedelic research among people who use psychedelics. Journal of Psychiatric Research June 2, 2026
- Hallucinogenic Therapy in Alzheimer's Disease targeting Mitochondria-Associated Membranes. Neuroscience April 6, 2026
Cites 16
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology November 8, 2017
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors Science February 16, 2023
and 11 more in the library