Understanding complexity of psychoactive mushrooms – precision medicine approach to Parkinson’s Disease

Parkinson’s Disease (PD) is a multifaceted and debilitating neurodegenerative disease with limited therapeutic options. PD is classified into familial and sporadic forms – both forms have underlying genetic alterations as gene mutations (familial; 23 genes identified) or gene expression alteration (sporadic) [ 1 ]. Familial PD contributes to PD research by driving our understanding of the underlying cellular and molecular mechanisms that underpin the cellular phenotypes exhibited in PD -alpha-synuclein aggregation (Lewy Bodies) and loss of dopaminergic neurons/dopamine release. PD patients seek alternative treatment options to alleviate their motor and non-motor symptoms, including changes in diet and use of specific supplements or plant-based controlled substances – cannabis and psychoactive mushrooms. Psychoactive mushrooms synthesise a variety of bioactive compounds from L-tryptophan into tryptamines, including psilocybin and psilocin. While their role in activating serotonin receptor is well known, recent studies show these tryptamines activate neuroplasticity pathways via TrkB receptor. As neurodegenerative diseases are underpinned by the loss of neuroplasticity and associated cell death, this project uses a precision medicine approach to investigate alignment of genetic make-up with targeted therapeutic approach using a well-defined pre-clinical model of disease. Project utilised SH-SY5Y cells overexpressing a range of different PD mutations and investigated rescue of alpha-synuclein aggregation and neurite outgrowth assays using three different mushroom extracts chosen based on traditional use (hot water) and published literature (ethanol and methanol). Preliminary results indicate phenotype rescues are mutant- and extract- specific – an outcome that allows further research into personalised therapeutics approach using controlled substances. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany