Regulation of neural connectivity and oscillations by cannabinoids: A review.

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.