Cannabidiol Enhances Exercise Endurance in Mice by Altering the Gut Microbiome

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In a recently published study (1), researchers examined the function of cannabidiol (CBD) in improving endurance exercise performance. As noted in the introduction, CBD has been previously connected with improved muscle repair after injury in athletes, and has been removed from the World Anti-Doping Agency’s “Prohibited List.” Additionally, exercise and gut microbiota are connected, with CBD being shown to alter the gut microbiota. This study, “Cannabidiol reshapes the gut microbiome to promote endurance exercise in mice,” examined exercise performance as influenced by CBD and the gut microbiome, and was published in Experimental & Molecular Medicine in February 2025.

For the first group of mice in this study, CBD was administered into the mice daily for four weeks at a dosage of 30 mg/kg. Treadmill performance was evaluated. In a second group of mice, an antibiotic, doxycycline, was administered at 40 mg/kg either in combination with CBD or by itself, during the treadmill testing period. The third group of mice was given microbes daily for four weeks, and their performance on the treadmill was compared to the mice given CBD.

An hour after the administration of CBD or bacterium, the testing of exercise performance on the treadmill began. Measurements of time and distance were taken over four weeks, along with respiratory exchange and biochemical analyses. Gastrocnemius (GAS) muscle tissue samples were also analyzed as well as genome sequencing.

Results included:

• Increased running distance and time to exhaustion was seen in mice given CBD and GAS muscles were shown to be more resistant to fatigue
• CBD was also found to enhance muscle oxidative capacity
• CBD also changed the gut microbiome without affecting body weight or food intake and was suggested that this contributed greatly to effects on exercise performance
• CBD was found to improve muscular endurance by enhancing mitochondrial biogenesis
• The effects of CBD were eliminated by antibiotics

Additionally, the researchers also isolated the strain KBP-1 from the mice with endurance enhancement and suggested further research: “Our results indicate that CBD treatment improved exercise performance and mitochondrial function in skeletal muscle in mice, which was mediated by changes in the gut microbiota. We identified a key bacterial responder, Bifidobacterium animalis, termed KBP-1, highlighting its potential as an option for promoting endurance exercise.”

Limitations to the study included a small sample size, which limits the ability of the results to be generalized. Also, the levels of branched-chain amino acid (BCAA) – which affect fatigue, muscle damage and more – produced by KBP-1 were not measured in serum or muscle tissue.

Reference

1. Chen, S.; Lee, YB.; Song, MY.; Lim, C.; Cho, H.; Shim, HJ.; Kim, JK.; Park, BH.; Kim, JK.; Bae, EJ. Cannabidiol reshapes the gut microbiome to promote endurance exercise in mice. Exp Mol Med. 2025. DOI: 10.1038/s12276-025-01404-5.