Radical Revelations: The Interplay of Nitrosative Stress, the Endocannabinoid System, and Treatment of Age-Related Disorders

The crosstalk between the endocannabinoid system (ECS) and reactive nitrogen species (RNS) has emerged as an important area of investigation in recent years. Although many aspects of this interaction remain elusive, accumulating evidence demonstrates that the ECS plays a critical role in regulating RNS-mediated signaling under physiological conditions. This modulation can be either inhibitory or stimulatory, depending on the specific receptor subtype, cell type, and tissue location involved. While ECS-RNS interactions support normal cellular homeostasis, their dysregulation contributes to various disease states, particularly neurodegenerative disorders. Studies in both rodent models and human subjects show that ECS modulation can reduce anxiety, attenuate neuroinflammatory responses, and slow disease progression in neurodegenerative conditions. This review examines how cannabinoid-based interventions modulate nitrosative stress and neuroinflammation in Alzheimer’s disease (AD) and Parkinson’s disease (PD), highlighting their potential as targeted therapeutics that address multiple pathological mechanisms simultaneously and may offer advantages over conventional treatment approaches.