Cannabinoids and Extracellular Vesicles as Potential Biomarkers and Therapeutic Targets in Neuropsychiatric...

Background and Objectives: Neuropsychiatric disorders pose a major global health challenge, marked by high prevalence, limited diagnostic precision, and suboptimal therapeutic outcomes. Current diagnoses remain primarily clinical, lacking objective biomarkers, while many patients experience poor remission rates and frequent relapse. The endocannabinoid system (ECS), a central regulator of synaptic plasticity, neuroinflammation, and stress responses, is increasingly implicated in depression, anxiety, schizophrenia, and neurodegenerative diseases. In parallel, extracellular vesicles (EVs) have emerged as critical mediators of intercellular communication and promising biomarker sources, as they reflect the physiological or pathological status of their cells of origin. This review examines the hypothesis that interactions between ECS signaling and EV-mediated communication form a convergent pathway shaping vulnerability and resilience in neuropsychiatric disorders, with potential implications for biomarker identification and therapeutic innovation. Methods: This hypothesis-driven review was developed using a narrative approach, focusing on the interface between cannabinoids and EVs in neuropsychiatric conditions. Relevant publications were identified through PubMed, Scopus, and Web of Science searches up to September 2025. Results: Emerging evidence indicates a bidirectional relationship between ECS activity and EV biology: endocannabinoids can be loaded into EVs to facilitate intercellular signaling, while phytocannabinoids such as THC and CBD can alter EV release and cargo composition. Conclusions: We propose a hypothesis-driven framework in which the possible interplay between cannabinoids and EVs may stimulate new research and support the development of biomarker-guided, personalized therapeutic strategies for neuropsychiatric disorders.