Skeleton muscles are a type of muscle tissue composed of skeletal muscle cells. Most skeletal muscles are attached to bones and are the most abundant tissue in the body, making up 40% of body weight.

In the field of sports, people have always been curious about how to improve athletic performance. The health of skeletal muscles is closely linked to exercise capacity and is made up of different types of muscle fibers, such as slow-twitch fibers (Type I) and fast-twitch fibers (Type II). These fiber types can change in response to various physical stimuli, such as endurance training, which increases the proportion of slow-twitch fibers.

In research on improving athletic performance, two key "helpers" have received significant attention: mitochondrial biogenesis and the related signaling pathways. AMPK (AMP-activated protein kinase), CREB (cAMP response element-binding protein), and PGC-1α (PPARγ coactivator-1α) play important roles, acting like "small switches" in the process of enhancing athletic performance by regulating various changes in muscles.

Previous studies have found that CBD has some impact on skeletal muscle function. In animal experiments, CBD has been shown to improve the muscle lipid profile in mice and rats fed a high-fat diet, promote skeletal muscle regeneration, and increase muscle strength. However, whether CBD can enhance endurance performance and the mechanisms behind it remain unsolved mysteries.

Meanwhile, scientists have discovered a close relationship between athletic performance and the gut microbiome. Some gut bacteria can help improve endurance and reduce inflammation, and exercise, in turn, can alter the composition of the gut microbiota. For example, supplementing long-distance runners with Bacteroides uniformis can promote glucose production in the liver, thereby enhancing endurance. In marathon runners, the presence of Veillonella atypica in the gut can convert lactate produced during exercise into propionate, extending endurance exercise time. Furthermore, CBD has also been found to alter the gut microbiome, improving cognitive function, metabolic syndrome, and autoimmune encephalomyelitis.

Given these factors, one might wonder: Can CBD enhance athletic performance by modulating the gut microbiome?

To find the answer, researchers from the Department of Biochemistry and Molecular Biology at Chonbuk National University Medical School in South Korea conducted in-depth research. Their findings were published in the journal Experimental & Molecular Medicine under the title "Cannabidiol reshapes the gut microbiome to promote endurance exercise in mice."


The study found that CBD can enhance the endurance performance of mice and also modulate the gut microbiome, with Bifidobacterium animalis KBP-1 playing a key role. This provides new insights and approaches for improving endurance performance.

To conduct this research, the scientists employed various techniques. In animal experiments, they carefully bred male C57BL/6J mice and observed the effects of orally administered CBD, antibiotics, or specific microorganisms on the mice's treadmill running performance. They also used treadmill exercise assessments, where mice underwent adaptive training on the treadmill followed by endurance tests, recording running time and distance.

For detection and analysis, they used indirect calorimetry to measure the mice's respiratory exchange ratio, providing insights into their energy metabolism. Biochemical analysis methods were employed to measure blood glucose, blood β-hydroxybutyrate, and blood lactate levels. Histological staining and immunofluorescence staining were used to observe muscle fiber types and mitochondria. 16S rDNA amplicon sequencing was used to analyze changes in the gut microbiome composition, and single bacterial isolation and whole-genome sequencing helped identify key microorganisms and their functions.

Now, let's take a look at the specific research results.


CBD Enhances Exercise Endurance and Promotes the Shift of Muscle Fiber Types from Glycolytic to Oxidative

The researchers first wanted to see if CBD could improve the exercise performance of mice. They placed 20-week-old C57BL/6 mice on a treadmill for one week of acclimation, running for 30 minutes each day at a speed of 10 meters per minute. After that, the mice were divided into two groups: one group was fed corn oil (VEH), and the other group was orally administered 30 mg/kg of CBD daily for 4 weeks. During this period, the mice underwent treadmill running tests every day. The results showed that the mice that received CBD had significantly improved endurance, running longer distances, and sustaining activity for longer periods, with no changes in body weight or food intake. Upon dissection, the muscles in the hind limbs of these mice appeared redder, indicating a shift in muscle fibers toward oxidative types. Further analysis revealed that, after CBD treatment, there was an increase in Type I and Type II oxidative fibers (MyHC-I and MyHC-IIa) in the gastrocnemius muscle (GAS), while Type II glycolytic fibers (MyHC-IIb) decreased. The mRNA expression of relevant genes also showed corresponding changes. Indirect calorimetry analysis further indicated that the CBD-treated mice had a lower respiratory exchange ratio (RER), suggesting they relied more on fatty acid oxidation for energy. Additionally, the GAS muscles in the CBD-treated mice exhibited stronger muscle contraction and were less prone to fatigue.


CBD Increases Mitochondrial Content and Oxidative Capacity and Activates the PKA-CREB-PGC-1α Pathway

The enhancement of muscle fiber oxidative capacity is closely related to mitochondrial biogenesis and function. Using electron microscopy, the researchers observed that the mitochondria between fused myofibrils in the muscle of CBD-treated mice were more abundant than in the control group, indicating an increased oxidative phosphorylation capacity.

Furthermore, after CBD treatment, the mitochondrial DNA content in the mice's muscles significantly increased, and the protein levels of mitochondrial respiratory chain complexes I-III and V (ATP synthase) were also elevated. The expression of related genes also increased, suggesting that CBD improved the muscle's oxidative capacity by promoting mitochondrial biogenesis and dynamic changes. Additionally, the researchers found that CBD activated AMPK and PKA, which led to increased phosphorylation of CREB and elevated levels of PGC-1α, further confirming CBD’s positive impact on mitochondrial biogenesis and muscle function.


CBD Alters Gut Microbiome Composition, and Antibiotic Treatment Inhibits Its Exercise Performance Enhancing Effect

Given the relationship between the gut microbiome and exercise performance, the researchers analyzed the 16S rRNA sequences of fecal samples from the mice to observe the effects of CBD on the gut microbiome.

The results showed that after CBD treatment, there were significant changes in the composition of the microbiome. At the phylum level, the relative abundance of Bacillota and Actinomycetota increased. At the family level, the proportion of Erysipelotrichaceae and Bifidobacteriaceae significantly increased, while the proportions of Oscillospiraceae and Prevotellaceae decreased. At the genus level, the proportions of Allobaculum, Faecalibaculum, and Bifidobacterium notably increased. Although the α-diversity index did not show significant changes, principal coordinate analysis revealed a clear difference in the microbiome composition between the CBD-treated group and the control group.

To explore the causal relationship between these changes and the improvement in exercise performance, the researchers treated the mice with both antibiotics (ABX) and CBD. After screening, they chose doxycycline because it could inhibit the bacteria increased by CBD, has minimal impact on the overall microbiome, and does not cause weight changes in the mice.

The results showed that when doxycycline was administered along with CBD, the mice’s running performance, oxidative muscle fiber density, and mitochondrial gene expression no longer increased. The respiratory exchange ratio did not decrease, and the activation of relevant signaling pathways was also suppressed. This indicates that changes in the gut microbiome play a key role in CBD’s enhancement of exercise performance.


Bifidobacterium animalis Significantly Increases After CBD Treatment, Improving Exercise Performance and Increasing Oxidative Muscle Fibers

The researchers isolated Faecalibaculum rodentium and Bifidobacterium animalis from the microbiota that significantly increased after CBD treatment.

They then orally administered these two microorganisms to the mice and compared the results with the CBD treatment group. The results showed that the mice that were orally administered Bifidobacterium animalis had significantly improved endurance, with longer running times and distances. Additionally, their muscle fibers shifted toward oxidative types, with an increased density of SDH-positive fibers, a reduced respiratory exchange ratio, lower blood lactate levels, and higher serum β-hydroxybutyrate (a ketone body). These effects were similar to those observed in the CBD treatment group. However, the mice that received Faecalibaculum rodentium did not show any improvement in exercise performance. This indicates that Bifidobacterium animalis can enhance exercise endurance by altering muscle fiber types and metabolic substrate utilization.


Bifidobacterium animalis KBP-1 Alters Energy Metabolism and Gut Microbiome

The researchers found that Bifidobacterium animalis B treatment lowered serum lactate levels and increased serum ketone body levels in the mice, which contributed to improved exercise endurance. 

To further understand the mechanism by which Bifidobacterium animalis B enhances endurance, the researchers conducted a whole-genome analysis and identified it as Bifidobacterium animalis KBP-1. Compared to other similar strains, they found that KBP-1 highly expressed genes related to branched-chain amino acid (BCAA) biosynthesis, release pumps, and lactate metabolism. These genes may play an important role in enhancing muscle endurance. For example, BCAAs can improve fatigue, reduce muscle damage, enhance exercise performance, and promote lipid oxidation during endurance exercise after muscle glycogen depletion.

Through a series of experiments, the researchers concluded that CBD can enhance endurance exercise performance in mice by activating the AMPK and PKA-CREB pathways, promoting mitochondrial biogenesis, and shifting muscle fibers toward oxidative types. Furthermore, the improvement in exercise performance by CBD largely depends on changes in the gut microbiome, with Bifidobacterium animalis KBP-1 playing a crucial role. It enhances exercise endurance by altering energy metabolism and the gut microbiome, potentially through the high expression of genes associated with BCAA synthesis and metabolism.


This study is highly significant. It not only reveals a new function and mechanism of CBD in enhancing endurance performance but also identifies Bifidobacterium animalis KBP-1 as a potential "helper" for improving endurance exercise. This provides new insights for athletes and fitness enthusiasts, suggesting that in the future, supplementing CBD or KBP-1 may enhance exercise performance.

However, the study does have some limitations, such as a small sample size and the lack of measurements of BCAA levels in serum and muscle tissues. These shortcomings also point to directions for future research. It is believed that, as research progresses, our understanding of exercise performance enhancement will deepen, and more effective methods will be found to help people improve their athletic capabilities.