Evaluating Psilocybin as a Treatment for Neuropsychiatric Symptoms in Parkinson’s Disease

Parkinson’s Disease (PD) is a progressive neurodegenerative disorder marked by motor symptoms due to dopaminergic degeneration and non-motor symptoms such as depression, anxiety, and cognitive impairment, which significantly affect patients' quality of life. Traditional dopaminergic therapies address motor symptoms but offer limited efficacy for neuropsychiatric manifestations. Psilocybin, a serotonergic compound with strong affinity for the 5-HT2A receptor, has emerged as a promising candidate for addressing the complex symptomatology of PD, including its neuropsychiatric components. This review examines the pharmacological effects of psilocybin, particularly its ability to modulate serotonergic and dopaminergic systems, enhance neuroplasticity, and reduce neuroinflammation, offering a potential therapeutic approach for PD. While clinical research in PD remains limited, evidence from related conditions such as Major Depressive Disorder (MDD) and Substance Use Disorder (SUD) supports the notion that psilocybin could modulate both motor and non-motor symptoms in PD. Furthermore, psilocybin’s ability to induce brain network hyperconnectivity and regulate dopamine release offers mechanistic insight into its potential benefits. Despite the promising neurobiological underpinnings, ethical concerns and regulatory constraints remain barriers to widespread clinical use. Future research should prioritize disease-specific trials to explore psilocybin’s therapeutic efficacy, optimal dosing, and safety profile in PD, potentially redefining the treatment landscape for this underserved population.