Cannabidiol and skeletal muscle insulin resistance: translational implications for exercise and rehabilitation...

Insulin Resistance (IR) is a central pathophysiological mechanism underlying obesity, type 2 diabetes mellitus, metabolic syndrome, and metabolic dysfunction-associated steatotic liver disease, with significant implications for skeletal muscle function, exercise capacity, and rehabilitation outcomes. Because skeletal muscle represents the primary site of insulin-stimulated glucose disposal, muscle insulin resistance is a key determinant of both metabolic health and physical performance. Cannabidiol (CBD), a non-intoxicating phytocannabinoid derived from Cannabis sativa, has attracted increasing scientific interest due to its anti-inflammatory, antioxidant, and pleiotropic signaling properties. This narrative review aims to examine the relationship between CBD and insulin resistance, with a particular focus on skeletal muscle biology and its relevance for exercise and rehabilitation medicine. A structured literature search was conducted using major biomedical databases, including PubMed, Scopus, and Web of Science, to identify relevant preclinical and clinical studies. Evidence was synthesized narratively, with emphasis on skeletal muscle insulin resistance, endocannabinoid system signaling, potential mechanisms of CBD action, and clinical outcomes. Preclinical data suggest that CBD may influence several pathways involved in skeletal muscle insulin resistance, including chronic low-grade inflammation, oxidative stress, lipotoxicity, and ceramide accumulation. However, current human studies remain limited and do not demonstrate consistent improvements in glycemic control or insulin sensitivity with CBD alone. Furthermore, evidence regarding its effects on muscle function, exercise performance, or rehabilitation outcomes is lacking. In conclusion, CBD represents a biologically plausible but clinically unproven modulator of skeletal muscle insulin resistance. At present, it should be considered an experimental adjunct rather than an established therapeutic strategy. Future research should focus on well-designed clinical trials integrating metabolic and functional endpoints to determine its potential role alongside exercise-based interventions in rehabilitation medicine.