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Regulation of Neural Connectivity and Oscillations by Cannabinoids: A Review
Gianluca Lavanco1, Valentina Castelli2, Anna Brancato1
1University of Palermo, Dept. of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties of Excellence "G. D'Alessandro", Piazza delle Cliniche 2, 90127 Palermo, Italy.
Abstract:
Brain oscillations represent frequency-specific neural phenomena essential for coordinating distributed brain activity and supporting cognition. The endocannabinoid system (ECS), particularly via cannabinoid receptor 1 (CB1R), plays a pivotal role in modulating neural oscillations through inhibitory circuit modulation, synaptic plasticity regulation, and long-range connectivity coordination. This review synthesizes current understanding of cannabinoid-oscillation interactions from a primarily mechanistic perspective, organized along a temporal framework: acute cannabinoid effects that directly engage CB1R-mediated circuit modulation; chronic adaptations that produce persistent oscillatory changes outlasting drug exposure; developmental vulnerability during prenatal and adolescent periods when cannabinoid exposure disrupts oscillatory circuit maturation; and aging-related ECS dysfunction in neurodegenerative conditions. Within this temporal structure, we examine specific cognitive domains and clinical conditions where mechanistic insights have translational relevance. Understanding the role of ECS as a modulator of oscillations will improve development of targeted cannabinoid-based therapeutics. We conclude by identifying critical knowledge gaps, including incomplete characterization of cell-type-specific CB1R functions and the mechanistic links between oscillatory dysregulation and specific psychiatric symptoms.
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