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Hepatocellular carcinoma (HCC) is the most common liver cancer (90% of cases) and the fourth leading cause of cancer deaths worldwide. Current treatment options only apply to the early stages of tumor development. Unfortunately, tumor recurrence occurs in half of the patients. Recently, an American team highlighted a clear link between human cannabis use and a 55% lower risk of developing hepatocellular carcinoma. Additional clinical studies will help better understand the mechanism by which various compounds, particularly CBD in cannabis, may regulate the development of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is responsible for 500,000 to 1 million deaths per year. In France, the mortality associated with HCC is about 8000 deaths per year. If HCC is diagnosed after onset of symptoms, the 5-year survival rate is estimated at 18%. Hepatocellular carcinoma (HCC), the most important primary liver cancer, is almost always a complication of a chronic liver disease called cirrhosis. The main causes of cirrhosis are excessive and prolonged alcohol consumption, chronic infections with hepatitis B and hepatitis C viruses, and the metabolic syndrome (overweight or obesity, diabetes, hypertension).
Cannabis is the third most commonly used psychoactive substance in the world after alcohol and tobacco. It has recently been considered for clinical applications. The World Health Organization (WHO) estimates that between 128 and 232 million people worldwide are currently using cannabis, and increasing legalization of cannabis is set to increase this number in the near future. Despite its widespread use, the clinical benefits of cannabis have yet to be studied and could potentially provide a solution to the lack of treatments for certain types of cancer.
In fact, in recent years, several clinical studies have tested the effectiveness of new agents that selectively target the carcinogenic process of hepatocellular carcinoma. Unfortunately, no significant improvement in patient prognosis has been achieved so far.
In this regard, a team of researchers from the Cleveland Clinic and Georgetown University Hospital in Washington DC evaluated the relationship between cannabis use and HCC in a cohort of over one million subjects. Your data will be published in the journal Kurus.
An extraordinary population study
To examine the possible association between cannabis and liver cancer, the authors selected patients with HCC who were or were not cannabis users from the National Inpatient Sample (NIS) database between 2002 and 2014.
Of the 101,231,036 adult NIS patients from 2002 to 2014, researchers identified 996,290 (1%) patients who used cannabis compared to 100,234,746 (99%) patients who did not use cannabis. The group of cannabis users had a higher prevalence of alcohol abuse, history of smoking, HBV, HCV and liver cirrhosis, precursor pathologies of hepatocellular carcinoma. Nonetheless, they had a lower prevalence of HCC, obesity and gallstones compared to the non-drinkers group.
In addition, the authors also identified 111,040 (0.1%) HCC patients, of whom 734 (0.7%) were cannabis users. Using multivariate logistic regression and after accounting for patient demographics, comorbidities, and hospital characteristics, they estimated that cannabis users were 55% less likely to develop HCC compared to non-cannabis users.
Cannabis as a remedy?
Cannabis is able to exert its effects through two active chemical compounds, tetrahydrocannabinol (THC) and CBD, which bind to their respective CB-1 and CB-2 cannabinoid receptors in the body. In the liver, CB-1 receptor signaling stimulates hepatic stellate cells, thereby promoting steatohepatitis—a chronic condition characterized by accumulation of fat in the liver (steatosis) and associated inflammation of the organ (hepatitis)—and hepatic fibrosis, a scarring process whose ultimate Development is cirrhosis, one of the main complications of many liver diseases. Conversely, activation of the CB-2 receptor reduces hepatic immune cell infiltration, oxidative stress, liver damage and fibrogenesis, resulting in inhibition of liver cirrhosis.
Additionally, some studies in mouse and rat cells have shown that cannabinoids can inhibit the growth of tumors by causing cancer cell death, blocking their division, or preventing angiogenesis (production of vessels to feed tumors) while protecting healthy cells .
Therefore, CB-1 and CB-2 have the potential to serve as therapeutic targets. Furthermore, the CB-2 agonist activity exerted by cannabis, specifically CBD, provides an explanation for the observations of the present study. Put simply, it would serve to protect against HCC, or at least slow the progression of the disease. In addition, the pharmaceutical development of compounds that display the dual effects of CB1 antagonism and CB2 agonism would be a major advance in the treatment of liver disease.
The authors conclude: To our knowledge, this is the first and largest inpatient cross-sectional population-based study investigating the association between cannabis use and HCC. Due to the cross-sectional design of our study, we cannot derive any direct causal effects. Therefore, we propose prospective clinical studies to better understand the mechanism by which various compounds, particularly CBD in cannabis, may regulate the development of hepatocellular carcinoma. “.
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