Cannabigerol Enhances Muscle Strength and Performance in Dexamethasone-Treated Mice

Abstract Sarcopenia is a major clinical condition associated with aging and is characterized by progressive loss of skeletal muscle mass and function. Resistance training is an effective intervention to counteract muscle atrophy; however, strategies that selectively enhance functional performance remain limited. Cannabigerol, a phytocannabinoid that is not a CB1 receptor agonist and therefore lacks psychotomimetic activity, has emerged as a potential modulator of neuromuscular function, although its role in skeletal muscle adaptation remains poorly understood. Here, we investigated the effects of resistance exercise and cannabigerol, alone and in combination, in a dexamethasone-induced model of muscle atrophy in mice. Animals received dexamethasone (20 mg/kg, i.p.) for 12 days and were subsequently subjected to a 4-week ladder-based resistance exercise protocol. Cannabigerol (10 mg/kg, i.p.) was administered on training days. Resistance exercise restored muscle morphology and improved fatigue resistance. In contrast, cannabigerol acted mainly on neuromuscular performance, increasing muscle power while producing only a small increase in fiber cross-sectional area. Cannabigerol potentiated training-induced power output, increasing performance by ∼55% in the first week and up to ∼87% after 4 weeks compared to exercise alone. In addition, cannabigerol increased peak grip strength (∼10%) and lowered post-exercise blood lactate in sedentary animals (∼48%). These findings show that resistance exercise and cannabigerol exert complementary effects on skeletal muscle─exercise promoting structural recovery and cannabigerol enhancing neuromuscular performance and lowering post-exercise lactate─and support further investigation of cannabigerol as an adjunct to exercise in glucocorticoid-induced muscle atrophy.