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Cannabis: the risk of liver cancer would be reduced by 55% for users

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Hepatocellular carcinoma (HCC) is the most common liver cancer (90% of cases), and represents the fourth leading cause of cancer death worldwide. Current treatment options apply only to the early stages of tumor development. Unfortunately, half of the patients will experience recurrence of the tumor. Recently, a US team highlighted a clear link between cannabis use in humans and a 55% lower risk of developing hepatocellular carcinoma. Additional clinical studies will help to better understand the mechanism by which various active ingredients, particularly the CBD in cannabis, possibly 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 8,000 deaths per year. If HCC is diagnosed after the onset of symptoms, 5-year survival is estimated at 18%. Hepatocellular carcinoma (HCC), the main 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 by the hepatitis B and hepatitis C viruses, and metabolic syndrome (overweight or obesity, diabetes, high blood pressure).

Cannabis is the third most consumed psychoactive substance in the world, after alcohol and tobacco. It has recently been considered for clinical applications. According to the World Health Organization (WHO), it is currently estimated that between 128 and 232 million people worldwide use it, and the increasing legalization of cannabis will increase this number in the near future. Despite its widespread use, the clinical benefits of cannabis have not yet been studied and could perhaps provide a solution to the lack of treatments for certain types of cancer.

In fact, in recent years, several clinical trials have tested the efficacy of new agents, selectively targeting the carcinogenic process of hepatocellular carcinoma. Unfortunately, so far no significant improvement in patient prognosis has been achieved.

In this context, a team of researchers affiliated with the Cleveland Clinic and Georgetown University Hospital in Washington DC evaluated the relationship between cannabis use and HCC in a cohort of more than one million subjects. Your data is published in the magazine curao.

An extraordinary population study

To study the possible relationship between cannabis and liver cancer, the authors selected from the National Inpatient Sample (NIS) database between 2002 and 2014, patients with HCC who were or were not cannabis users.

Of 101,231,036 adult patients with NIS between 2002 and 2014, the researchers identified 996,290 (1%) patients who used cannabis, compared with 100,234,746 (99%) patients who did not use cannabis. The group of cannabis consumers had a higher prevalence of alcohol abuse, a history of smoking, HBV, HCV and liver cirrhosis, precursor pathologies of hepatocarcinomas. However, they had a lower prevalence of HCC, obesity, and gallstones compared to the non-drinking group.

In addition, the authors also identified 111,040 (0.1%) patients with HCC, of ​​whom 734 (0.7%) were cannabis users. Using multivariate logistic regression and after adjusting 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 cure?

Cannabis can exert its effect 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, thus promoting steatohepatitis —a chronic disease with accumulation of fat in the liver (steatosis) associated with inflammation of the organ (hepatitis)— and liver fibrosis, scarring process whose final evolution is cirrhosis, an important complication of many liver diseases. In contrast, activation of the CB-2 receptor decreases hepatic immune cell infiltration, oxidative stress, liver damage, and fibrogenesis, leading to inhibition of liver cirrhosis.

In addition, some studies in mouse and rat cells have shown that cannabinoids can inhibit tumor growth, causing the death of cancer cells, blocking their division or preventing angiogenesis (production of vessels to nourish the tumor) while protecting healthy cells .

Therefore, CB-1 and CB-2 have the potential to serve as therapeutic targets. Furthermore, the CB-2 agonistic activity exerted by cannabis, particularly CBD, offers an explanation for the observations of the present study. In simple terms, it would serve as protection against HCC or at least slow down the progression of the disease. In addition, the pharmaceutical development of compounds that exert the double effect of CB1 antagonism and CB2 agonist would represent a great advance in the treatment of liver diseases.

The authors conclude: To our knowledge, this is the first and largest population-based cross-sectional study of hospitalized patients to explore the association between cannabis use and HCC. Due to the cross-sectional design of our study, we cannot extract direct causal effects. Therefore, we suggest prospective clinical studies to better understand the mechanism by which various active ingredients, especially the CBD in cannabis, possibly regulate the development of hepatocellular carcinoma. “.

Source: Cureo

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