Cannabis oil modulates liver alterations and endocannabinoid system changes in a female rat model of diet-induced MASLD

• Autores: Degrave, Valentina; Vega Joubert, Michelle Berenice; Ingaramo, Paola I.; Sedan, Daniela Yazmine; Andrinolo, Darío; Mac Loughlin, Tomás Mariano; D’Alessandro, María Eugenia; Oliva, María Eugenia
• Año de publicación: 2026
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Salud; Biología; Cannabidiol (CBD); Cannabis oil; Endocannabinod system; MASLD; Metabolic syndrome
• Institución: Universidad Nacional de La Plata

Introduction: Metabolic dysfunction–associated steatotic liver disease (MASLD) is closely linked to alterations in liver lipid metabolism, oxidative stress, fibrosis, and dysregulation of the endocannabinoid system (ECS). Although increasing evidence supports a role for cannabinoids in metabolic disorders, most preclinical studies have been conducted in male models, leaving female-specific responses largely unexplored. Methods: This study evaluated the effects of oral administration of a fullspectrum cannabis oil (CBD:THC 2:1) on MASLD-related alterations and ECS regulation in female Wistar rats fed a sucrose-rich diet (SRD). Rats were assigned to reference diet (RD), SRD, or SRD plus cannabis oil (1 mg/kg/day) for 3 weeks. Results: SRD-fed rats developed liver steatosis and increased NAFLD activity score (NAS), accompanied by enhanced de novo lipogenesis, reduced mitochondrial fatty acid oxidation, increased oxidative stress, early fibrotic changes, and ECS overactivation. 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. Discussion: 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.
Centro de Investigaciones del Medioambiente