Effects of five cannabis oils with different CBD:THC ratios and terpenes on hypertension, dyslipidemia, hepatic steatosis, oxidative stress, and CB1 receptor in an experimental model

Background: Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder caused by oxidative stress and dysregulation of lipid metabolism. The endocannabinoid system (ECS), particularly the type 1 cannabinoid (CB1) receptor, plays a crucial role in NAFLD progression. Cannabinoids, such as cannabidiol (CBD) and tetrahydrocannabinol (THC), along with terpenes, such as beta-myrcene and d-limonene, have shown potential therapeutic effects on liver health, particularly in reducing oxidative stress and modulating lipid metabolism. This study aimed to analyse the effects of five cannabis oils (COs), each with different CBD:THC ratios and terpenes content, on hypertension, dyslipidemia, hepatic steatosis, oxidative stress, and CB1 receptor expression in an experimental model of NAFLD induced by a sucrose-rich diet (SRD) in Wistar rats for 3 weeks. Methods: Male Wistar rats were fed either a: 1) reference diet (RD; standard commercial laboratory diet) or a: 2) sucrose-rich diet (SRD) for 3 weeks. 3 to 7 SRD+CO as following: 3) SRD+THC; 4) SRD+CBD; 5) SRD+CBD:THC 1:1; 6) SRD+CBD:THC 2:1; and 7) SRD+CBD:THC 3:1. The COs were administered orally at a dose of 1.5 mg total cannabinoids/kg body weight daily. The cannabinoid and terpenes content of all COs used in the study was determined. The terpenes found in COs were beta-myrcene, d-limonene, terpinolene, linalool, beta-caryophyllene, alpha-humulene, (-)-guaiol, (-)-alpha-bisabolol. During the experimental period, body weight, food intake and blood pressure were measured. Serum glucose, triglyceride, total cholesterol, uric acid, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AP) levels were evaluated. Liver tissue histology, NAFLD activity score (NAS), triglyceride and cholesterol content, lipogenic enzyme activities, enzyme related to mitochondrial fatty acid oxidation, reactive oxygen species (ROS), thiobarbituric acid reactive substance (TBARS), and antioxidant enzyme activities were also evaluated. The CB1 receptor expression was also determined. Results: The results showed that SRD-fed rats developed hypertension, dyslipidemia, liver damage, hepatic steatosis, lipid peroxidation, and oxidative stress. This was accompanied by upregulation of liver CB1 receptor expression. CBD-rich CO, CBD:THC 1:1 ratio CO; CBD:THC 2:1 ratio CO and CBD:THC 3:1 ratio CO showed antihypertensive properties. THC-rich CO, CBD:THC 1:1 ratio CO; CBD:THC 2:1 ratio CO showed the greatest beneficial effects against hepatic steatosis and liver damage. All COs exhibited antioxidant effects in liver tissue. This was associated with normal liver CB1 receptor expression. Conclusions: This study demonstrated that COs, particularly THC-rich CO, CBD:THC ratio 1:1 CO, CBD:THC ratio 2:1 CO and terpenes, can effectively reduce dyslipidemia, liver damage and hepatic steatosis in SRD-induced NAFLD. COs with a higher proportion of CBD in their composition showed antihypertensive properties. All the COs exhibited antioxidant properties. These findings suggest that COs, especially those with CBD:THC ratios of 1:1 and 2:1 and terpenes, may represent a promising therapeutic approach for managing NAFLD and preventing its progression to more severe liver disease.