The three main causes of inflammation and chronic damage to the liver are viral hepatitis, alcohol consumption, and non-alcoholic fatty liver disease, all of which can cause liver cirrhosis and hepatocellular carcinoma (HCC) [1], [2]. HCC is the fifth most common cancer in the adult male population and the second most common deadly cancer. HCC is the ninth diagnosed cancer and the sixth cancer leading to death in adult women. In most cases, HCC, as an invasive cancer, is the result of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and 80 % of HCC cases are caused by HBV hepatitis. Generally, the higher prevalence of HCC in Asia and Africa is due to a higher rate of infection with HBV and HCV. Chronic hepatitis tends to become HCC in four years. The vertical transfer of infection from mother to fetus in endemic areas increases the incidence of HBV carcinogenesis [3], [4]. The most common cause of HCC in Iran is HBV infection, which occurs in 1.4 per 100,000 men and 1.9 per 100,000 in women. On average, >887,000 people die each year from complications of HBV infection, including cirrhosis and HCC; HBV is responsible for 45 % of HCC cases and 30 % of cirrhosis cases [5].

Cannabinoids are an active compound of a plant called hemp. Cannabis, also called marijuana, has been used for medicinal purposes or in religious ceremonies in the West. Recognizing cannabinoid receptors in the brain over the past 30 years has uncovered their importance in health and disease [6]. Cannabinoid receptors have two pairs of G proteins, called CB1 and CB2. The major effects of cannabinoids, in addition to their environmental effects, depend on the activity of CB1 receptors [6], [7].

Cannabinoid receptors are part of the cannabinoid system. Endocannabinoids are involved in making and destroying CB receptors in the brain and surrounding tissues as well as in the liver. Endocannabinoid systems play key roles in biological processes such as metabolism, energy balance, and immune responses as well as in the pathogenesis of various diseases such as cancer, neurological disorders, and cardiovascular disease [8]. In particular, the endocannabinoid system plays an important role in the pathophysiological processes associated with acute and chronic liver disease including stimulating inflammation, injury, and liver fibrosis. CB1 and CB2 receptors in the normal liver show little response to endocannabinoids but are empirically strongly effective in regenerating damaged liver tissue and combating cirrhosis due to HBV and alcohol [9].

CB1 receptors are located in hepatocytes and stellar and endothelial cells, which promote the development of alcoholic and non-alcoholic fatty liver and increased liver fibrosis. It seems CB1 may act as an anti-inflammatory, liver-protective, and anti-fibrous agent in the liver. CB1 and CB2 receptors maintain a complex balance with conflicting effects on the liver. Studies have shown that, in addition to the direct effect on liver cell proliferation, CB1 may also affect suppression of the immune system. With antagonistic effects of CB1 and agonist effects of CB2, this relationship can be observed in liver cancer [10]. This study aimed to examine the immunoexpression of CB1 receptors in the livers of patients with HBV-related HCC in comparison with HCC and chronic HBV as well as healthy people.