As one of the largest organ systems, skeletal muscle accounts for approximately 40 % of the mammalian body mass [1], and its function is closely related to competitive level and body health, which are based on the contractile ability of the muscle [2]. Mitochondria are important intracellular powerhouses that produce adenosine triphosphate (ATP) to provide a source of power for the contraction of skeletal muscles to match the demands imposed by physical activity and exercise training. Adverse stress stimuli, such as aging, excessive production of reactive oxygen species (ROS), and Ca2+ overload, which will increase membrane permeability and fluidity of the mitochondrial membrane, disrupting of mitochondrial structure leading to mitochondrial dysfunction [3]. On the one hand, skeletal muscle mitochondrial dysfunction may cause chronic diseases related to muscle health, such as sarcopenia, obesity and type 2 diabetes (T2D) [2,4,5]; on the other hand, it may make the body easily enter a state of exhaustion, affecting the effect of exercise training, and even causing exercise injury [[6], [7], [8]].

Exercise training is an effective way to promote muscle health and is widely accepted due to its economic benefits. However, it should not be ignored that due to individual differences, the choice of exercise intensity and time is still worth exploring. Moderate exercise can help skeletal muscle mitochondria (quantity, quality and function) undergo adaptive changes, excessive exercise training may cause mitochondrial dysfunction and damage skeletal muscle health [3,9]. The mechanism of mitochondrial damage caused by excessive exercise training, may include two aspects: (1) material production changes after exercise (e.g. ROS, Ca2+, NO), and (2) excessive exercise leads to disorders of the mitochondrial quality control system (MQCS) [3]. MQCS, a series of adaptive responses that preserve mitochondrial structure and function, include mitochondrial biogenesis, mitochondrial fusion/fission and mitophagy [10]. Mitochondrial biogenesis synthesizes new mitochondria, promotes the expansion of an existing mitochondrial network. Mitochondrial quality is more finely adjusted by reshaping mitochondrial structures that are controlled by fusion/fission, as well as mitophagy [11]. However, excessive exercise training may cause excessive mitophagy, as well as inhibition of biosynthesis, fusion/division processes [12]. Mitophagy is a “self-eating” process, excessive mitophagy leading to mitochondrial dysfunction. Therefore, inhibiting excessive mitophagy may be a potential mechanism to improve mitochondrial function.

Cannabidiol (CBD) is a nontoxic component extracted from cannabis. Unlike tetrahydrocannabinol (THC), CBD does not cause psychotomimetic abuse, and thus, the safety of CBD products can be guaranteed [13]. Although the improvement effect of CBD on exercise performance and recovery has been confirmed in recent years, its impact mechanism of the physiological, physical, and cognitive effects are not fully understood [14,15]. We noticed that an increasing number of studies have reported the impact of CBD on the mitochondrial quality control system [16]. Several reports have demonstrated that CBD improves the function of nerve cells, cardiomyocytes, and liver cells by regulating mitophagy or biogenesis [[17], [18], [19], [20], [21]]. However, there is no clear evidence of the relationship between CBD and exercise induced mitochondrial dysfunction in skeletal muscles.

In this study, we assessed CBD treatment changes in the mitochondrial structure and function of skeletal muscle. Subsequently, based on RNA sequencing technology, we found that mitochondrial dysfunction is associated with excessive autophagy/mitophagy. Finally, the molecular mechanism by which CBD inhibits mitochondrial autophagy was further confirmed through qRT-PCR and Western Blot results. This discovery not only provides experimental basis for the medicinal treatment of exercise-induced skeletal muscle injury by CBD, but may also provide new ideas for improving skeletal muscle dysfunction caused by excessive mitophagy.