Cannabis oil administration improved liver lipid metabolism, reduced NAS and fibrosis markers, attenuated lipid peroxidation and oxidative stress, increased NrF2 and decreased NF-κB p65 expression, and normalized hepatic CB1 expression and circulating endocannabinoid levels.<h4>Discussion</h4>These findings demonstrate that full-spectrum cannabis oil is associated with improved MASLD-related outcomes and modulation of ECS tone in a female-specific model of diet-induced metabolic liver disease. The gene discussed is NFKB1; the disease is metabolic dysfunction-associated steatotic liver disease.