Exploring Ayahuasca Multitarget Potential in Neuropsychiatric Disorders: Integrated Insights Towards Drug Discovery

Abstract Purpose of Review This review integrates evidence from the literature with network pharmacology tools to explore the decoction’s multitarget potential and provide multilevel insights into its therapeutic role in neuropsychiatric disorders. Recent Findings Neuropsychiatric disorders remain a significant health burden, underscoring the limitations of single-target pharmacotherapies and the urgent need for effective multitarget approaches. Recent findings have unveiled that Ayahuasca, a traditional psychoactive decoction, is a promising therapeutic intervention in neuropsychiatric disorders. Yet, the molecular targets and pathways underlying its long-reported therapeutic effects remain incompletely understood. Summary Our literature search and analysis reveal a comprehensive network of interactions between ayahuasca’s bioactive compounds, including tryptamines and β-carboline alkaloids, with receptor/enzyme-based targets. These were supported by G-protein-coupled amine receptor and serine/threonine kinase activities, as revealed by functional enrichment analysis. Ayahuasca’s role in neuropsychiatric disorders may involve the activities of hub genes, including ALB, AKT1, HSP90AA1, EGFR, PTGS2, MMP9, SIRT1, MAOA, PRKACA, and PARP1, that interact within receptor, monoaminergic, and calcium signalling pathways. Although variability in ayahuasca composition and algorithmic complexities constitute limitations, current findings offer molecular insights for advancing drug discovery and development in neuropsychiatric disorders.