Cannabidiol as a modulator of NLRP3 inflammasome: Mechanistic insights and therapeutic potential

Dysregulated activation of the NLRP3 inflammasome is a central driver of chronic inflammatory, neurodegenerative, metabolic, and autoimmune diseases, contributing significantly to the global burden of disease and reduced quality of life. Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa , has emerged as a promising complementary and integrative therapeutic agent due to its broad anti-inflammatory and immunomodulatory properties. This narrative review synthesizes current mechanistic and translational evidence demonstrating that CBD modulates NLRP3 inflammasome activity through multiple interconnected pathways. These include suppression of NF- κ B–mediated priming, attenuation of mitochondrial dysfunction and reactive oxygen species generation, regulation of ionic fluxes, and enhancement of autophagic clearance of inflammasome activators. Collectively, these actions lead to reduced caspase-1 activation and decreased release of interleukin-1 β and interleukin-18, conferring protective effects in preclinical models of neuroinflammation, colitis, metabolic dysfunction, and organ injury. Despite robust preclinical support, clinical translation of CBD remains constrained by poor oral bioavailability, extensive first-pass metabolism, and formulation-dependent pharmacokinetics highlighting the need for innovative, affordable, and accessible pharmaceutical technologies. Emerging pharmaceutical strategies, including nano-delivery systems and advanced formulations, offer potential solutions to these limitations. Viewed through a systems-oriented pharmacological framework, CBD represents a plant-based, multi-target modulator capable of regulating complex inflammatory networks rather than single molecular targets. While existing evidence supports its therapeutic promise, biomarker-driven clinical trials are essential to establish its efficacy and clinical relevance in inflammasome-driven diseases.