“Introduction/aims: Duchenne muscular dystrophy (DMD) is caused by pathogenic variants in the DMD gene, making muscle fibers susceptible to contraction-induced membrane damage. Given the potential beneficial action of cannabidiol (CBD), we evaluated the in vitro effect of full-spectrum CBD oil on the viability of dystrophic muscle fibers and the in vivo effect on myopathy of the mdx mouse, a DMD model.
Methods: In vitro, dystrophic cells from the mdx mouse were treated with full-spectrum CBD oil and assessed with cell viability and cytotoxic analyses. In vivo, fourteen-day-old mdx mice received 10 mg/kg/day of the full-spectrum CBD oil for 14 days. We analyzed creatine kinase (CK) levels, liver damage markers, and histopathology of the diaphragm (DIA) and quadriceps (QUA [myonecrotic fibers with positive IgG staining, regenerated fibers/central nuclei, the minimum Feret’s diameter, the fibrosis area, the inflammatory area, the presence of macrophages, and NF-kappa B content]).
Results: In vitro treatment with full-spectrum CBD oil showed a dose-dependent cytotoxic effect; however, in vivo 10 mg/kg treatment was safe and effectively improved DMD histopathological assessment parameters in DIA and QUA: reduction of central nuclei: 1.7% ± 2.0% versus 22.4% ± 5.3% and 11.1% ± 10.7% versus 32.3% ± 4.6%; reduction of IgG+ myofibers: 0.6% ± 0.7% versus 8.4% ± 1.6% and 0.9% ± 0.3% versus 7.5% ± 1.0%; increase in myofiber size: 85.2 ± 3.2 versus 64.3 ± 4.0 μm and 106.5 ± 8.6 versus 81.2 ± 4.8 μm; decrease in inflammatory area: 6.2% ± 2.7% versus 15.1% ± 2.6% and 5.3 ± 4.1 versus 17.3% ± 2.8%; reduced macrophage area: 0.05% ± 0.1% versus 10.8% ± 4.3% and 1.0% ± 0.7% versus 10.3% ± 4.9%; NF-κB levels: 0.6% ± 0.1% versus 1.7% ± 0.2% and 1.7% ± 0.1% versus 5.2% ± 2.1%; and fibrosis: 5.6% ± 1.8% versus 12.0% ± 3.7% and 1.3% ± 0.5% versus 4.7% ± 1.5%. It also reduced serum CK.
Discussion: Full-spectrum CBD oil may represent a promising new approach to treating DMD, but its potential toxicity must be considered.”
“The endocannabinoid system refers to a widespread signaling system and its alteration is implicated in a growing number of human diseases.
However, the potential role of endocannabinoids in skeletal muscle disorders remains unknown. Here we report the role of the endocannabinoid CB1 receptors in Duchenne’s muscular dystrophy.
In murine and human models, CB1 transcripts show the highest degree of expression at disease onset, and then decline overtime. Similar changes are observed for PAX7, a key regulator of muscle stem cells. Bioinformatics and biochemical analysis reveal that PAX7 binds and upregulates the CB1 gene in dystrophic more than in healthy muscles.
Rimonabant, an antagonist of CB1, promotes human satellite cell differentiation in vitro, increases the number of regenerated myofibers, and prevents locomotor impairment in dystrophic mice.
In conclusion, our study uncovers a PAX7-CB1 cross talk potentially exacerbating DMD and highlights the role of CB1 receptors as target for potential therapies.”
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