The dual roles of natural cannabidiol in combating oxidative stress and inflammation: A potential intestinal guardian

Cannabidiol (CBD), a non-psychoactive and non-addictive phytocannabinoid derived from Cannabis sativa L., has attracted increasing attention for its therapeutic potential in intestinal diseases. Accumulating evidence indicates that CBD exerts prominent antioxidant and anti-inflammatory effects within the gastrointestinal tract. Oxidative stress and redox imbalance are key drivers of epithelial barrier dysfunction, chronic inflammation, and disease progression in disorders such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). This review focuses on the redox-related mechanisms underlying CBD's intestinal protective actions, highlighting its ability to regulate reactive oxygen species (ROS) production, activate the Nrf2-Keap1 antioxidant pathway, and modulate redox-sensitive inflammatory signaling, including NF-κB and the NLRP3 inflammasome. In parallel, CBD engages the endocannabinoid system (ECS) and related receptors to preserve epithelial barrier integrity, regulate gut microbiota composition, and modulate intestinal oxidative stress and inflammation. We further discuss emerging evidence linking CBD's regulation in the gut to systemic effects along the gut-organ axis, including the gut-brain and gut-liver axes. Overall, this review synthesizes current evidence on how CBD integrates redox modulation, inflammation control, and intestinal barrier protection, providing a mechanistic framework for its potential application in intestinal disease and health.