Comparing psilocybin to metformin as neuroprotective agents against Parkinson's dementia: A systematic review of evidence and efficacy

Background & aim: 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.

Methods: 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.

Results: 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-HT_2A receptor activation, ultimately increasing the release of brain derived neurotropic factor (BDNF) and the reduction of α-synuclein accumulation.

Conclusion: 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.