Review of the Molecular Processes by Which Cannabidiol Can Impact Muscle Metabolism, Inflammation, Tissue Repair, and Anabolism By Moniek Schouten, Sebastiaan Dalle, and Katrien Koppo First Published Online: December 5, 2022https://doi.org/10.1089/can.2022.0220 View Article Permissions & Citations Share Summary Background Cannabidiol (CBD), the non-psychoactive compound found in cannabis, has seen an upsurge in popularity in recent years, particularly among athletes. The World Anti-Doping Agency’s decision to remove CBD from its list of prohibited substances has significantly contributed to this trend. Athletes are increasingly using this compound due to its reputed benefits for muscle recovery and pain reduction, especially following strenuous physical activities. However, despite its growing popularity, a lack of concrete evidence exists to support these claims. The research into CBD’s mechanism of action remains nebulous, and the processes by which it enhances muscle recovery are still to be elucidated. This gap in knowledge prompts the need for further scientific research and the generation of evidence-based data to substantiate the claims about the muscle recovery benefits of CBD. The review we are discussing herein aims to shed light on the current understanding of CBD’s impact on skeletal muscle tissue. The focus will be on the underlying processes, molecular targets, and the wide array of receptor families believed to be instrumental in facilitating CBD’s physiological effects. Methods and Findings The review summarizes both in vivo and in vitro studies that have been conducted to explore CBD’s influence on various aspects, such as skeletal muscle metabolism, inflammation, tissue repair, and anabolism. Also included are human intervention trials that have studied the potential effects of CBD supplementation on muscle recovery. Interestingly, CBD has been observed to augment the expression of metabolic regulators in the muscle tissue of obese mice. Some of these metabolic regulators include Akt and glycogen synthase kinase-3. Furthermore, CBD treatment in rodent models has been shown to reduce muscle inflammation following eccentric exercise. This action is attributed to the downregulation of nuclear factor kappa B (NF-κB), a protein complex that plays a crucial role in cell signaling and inflammation, in muscle dystrophy and obesity models. Another intriguing finding is that CBD does not seem to influence in vitro or in vivo muscle anabolism. However, it has been found to enhance satellite cell differentiation in dystrophic muscles. This effect contributes to muscle growth and repair, which are vital for muscle recovery. Human studies have presented some evidence that CBD supplementation may improve muscle recovery and performance. However, the dosages of CBD used in these studies varied significantly, and there are several methodological issues that need to be addressed. These discrepancies and methodological challenges make it difficult to extract definitive conclusions from the existing data. Conclusion The potential of CBD as an effective supplement for enhancing muscle recovery is indeed promising. Its suggested effects on metabolic regulators and inflammation, as well as its potential role in aiding tissue repair, make it an intriguing area of research. Nonetheless, this field of study is still in its infancy, and future studies are warranted. They will serve to further delve into the molecular and functional effects of CBD in response to exercise and explore its potential ergogenic benefits. By doing so, it would be possible to paint a more definitive picture of CBD’s role in muscle recovery and sports performance.