Impact of CB1 receptor antagonism on skeletal muscle hypertrophy and metabolic health: a systematic review of preclinical studies.

Abstract

The endocannabinoid system (ECS), regulating such processes as energy homeostasis, inflammation, and muscle function, centers around cannabinoid receptors, including CB1. These receptors are mainly located in the central nervous system and skeletal muscles. Hyperactivity of CB1 receptors is linked to metabolic disorders and chronic inflammation, highlighting their potential as therapeutic targets for muscle hypertrophy and metabolic health. This systematic review, registered with PROSPERO (CRD42023462735), follows PRISMA-P guidelines and uses the PICO framework. It evaluates the effects of CB1 receptor antagonism on muscle hypertrophy in animal models and cell lines. Interventions include pharmacological antagonists, genetic modifications, and exercise-induced antagonism. A comprehensive search of databases such as PubMed, EMBASE, CINAHL, and SPORTDiscus, supplemented by gray literature and reference lists, yielded 571 references. From these, ten studies were selected, involving 338 rodents, using CB1 antagonists like rimonabant and AM251. The findings suggest that CB1 receptor antagonism enhances insulin sensitivity and glucose tolerance, reduces body fat, and promotes muscle growth through pathways such as PI3K/Akt and mTOR, as well as by improving autophagy and mitochondrial function. This review proposes CB1 receptor antagonism as a promising approach for enhancing muscle hypertrophy and improving metabolic health, with potential applications in treating such conditions as obesity, type 2 diabetes, and sarcopenia. Future research should aim to standardize intervention protocols and explore integrated therapies to fully harness the benefits of CB1 modulation.