Treatment With Full‐Spectrum Cannabidiol Oil Improved the Pathological Findings of Dystrophic Mutant Mice
Laís Leite Ferreira, Fabricio Souza Gomes, Beatriz Godinho Nascimento, Wagner Corsini, Luis Felipe Cunha dos Reis, João Marcos Oliveira‐Silva, Josie Resende Torres da Silva, Marcelo Lourenço da Silva, Angel Maurício Castro Gamero, Túlio de Almeida HermesABSTRACT
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.