A study published in 2024 investigated how cannabidiol (CBD), a non-psychoactive compound derived from the cannabis plant, affects physical endurance in mice. Researchers observed that CBD administration made skeletal muscles more resistant to fatigue and improved mitochondrial function, the primary energy-producing structures within cells. These beneficial effects were found to depend heavily on CBD-induced changes in the gut microbiome, with one specific bacterial strain, Bifidobacterium animalis KBP-1, playing a central mediating role.
Background on CBD and Muscle Physiology
CBD, unlike tetrahydrocannabinol (THC), does not produce psychoactive effects. It has been extensively researched for anti-inflammatory, neuroprotective, and anticonvulsant properties. Following its removal from the World Anti-Doping Agency’s prohibited list, interest has grown in its potential as a legal performance-enhancing aid. Skeletal muscle contains slow-twitch fibers (optimized for sustained, endurance-type activity) and fast-twitch fibers (suited for explosive power). Endurance training typically shifts fiber composition toward the more fatigue-resistant slow-twitch type. The study examined whether CBD could induce similar adaptations and whether the gut microbiota contributes to this process.
Study Design
Researchers divided laboratory mice into multiple groups. Some received daily oral CBD (30 mg/kg) for four weeks, others received CBD plus the broad-spectrum antibiotic doxycycline to deplete gut bacteria, and additional groups were supplemented with specific bacterial strains. Endurance capacity was assessed via treadmill running to exhaustion, measuring both time and distance covered.
Additional analyses included:
• Muscle fiber typing in the gastrocnemius muscle
• Mitochondrial density and respiratory function
• Gut microbiome composition via 16S rRNA sequencing and metagenomics
• Blood metabolites (glucose, lactate, ketones)
Key Findings
1 CBD significantly improved exercise endurance: CBD-treated mice ran substantially longer and farther before exhaustion than controls. Their muscles appeared redder (indicative of higher myoglobin and mitochondrial content), showed an increase in slow-twitch (type I and IIa) fibers, and a corresponding decrease in fast-twitch (type IIb) fibers. Muscles also displayed greater fatigue resistance and stronger force generation.
2 CBD enhanced mitochondrial biogenesis and function: Treated muscles exhibited higher mitochondrial density, improved oxidative capacity, and activation of key regulatory pathways (AMPK, PKA, and PGC-1α), all of which support greater energy efficiency during prolonged exercise.
3 Gut microbiota was essential for CBD’s effects: When gut bacteria were depleted using doxycycline, all endurance, fiber-type, and mitochondrial benefits of CBD were completely abolished, proving that an intact microbiome is required.
4 CBD remodeled the gut microbiome: CBD increased the abundance of bacteria from the families Erysipelotrichaceae and Bifidobacteriaceae, particularly the genera Faecalibaculum and Bifidobacterium.
5 Bifidobacterium animalis KBP-1 alone recapitulated CBD’s benefits: Oral administration of the single strain KBP-1 (isolated from CBD-treated mice) produced endurance improvements comparable to CBD itself, including enhanced running performance, reduced blood lactate accumulation, elevated circulating ketones, and promotion of fatigue-resistant muscle fibers. In contrast, supplementation with Faecalibaculum rodentium had no significant effect.
6 Mechanistic insight into KBP-1: Genomic analysis revealed that KBP-1 possesses genes enabling lactic acid metabolism and synthesis of branched-chain amino acids (BCAAs), compounds known to delay fatigue and support muscle endurance during prolonged exercise.
7 Short-chain fatty acids were not the primary mediators: Although a modest rise in circulating propionic acid was noted, its magnitude was insufficient to account for the observed performance gains.
Interpretation
The study demonstrated in mice that CBD enhances exercise endurance primarily through gut-microbiome-dependent mechanisms. It promotes a shift toward fatigue-resistant muscle fibers, increases mitochondrial efficiency, and enriches the gut with beneficial bacteria—most notably Bifidobacterium animalis KBP-1—which appears to mediate many of these adaptations via lactate metabolism and BCAA production. While direct effects of CBD on muscle cannabinoid receptors cannot be excluded, the microbiota emerged as the dominant pathway in this experimental model.
Limitations and Future Directions
The researchers acknowledged limitations, including the relatively small sample size and the lack of direct measurement of tissue BCAA levels. Future work will involve larger cohorts, additional bacterial strains, and eventual translation to human studies to determine whether CBD and/or probiotic supplementation with strains such as KBP-1 can safely and effectively improve endurance performance in people.
Conclusion
This research provides experimental evidence that CBD improves exercise endurance in mice largely by reshaping the gut microbiome and enriching it with Bifidobacterium animalis KBP-1. These findings open new avenues for microbiome-targeted interventions and CBD-based strategies to enhance physical stamina, particularly in endurance sports.
