Researchers have discovered that cannabis use may reduce, or even prevent, the onset of liver cancer in patients with liver cirrhosis. The research is based on a study of 101,231,036 patients between 2002-2014. The theory is that cannabinoids binding to CB-2 receptors decrease hepatic immune cell infiltration, oxidative stress, and fibrogenesis, thus inhibiting liver cirrhosis leading to cancer.
Hepatocellular carcinoma (HCC) is the most common liver cancer (90% of cases), representing the fourth leading cause of cancer death worldwide. Unfortunately, current treatment options apply only to the early stages of tumor development, and half of all patients will experience tumor recurrence.
Recently, an American team highlighted a clear link between cannabis consumption in humans and a 55% lower risk of developing hepatocellular carcinoma. Additional clinical studies will help better understand how various active ingredients, particularly CBD in cannabis, may regulate the development of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC), the leading liver cancer, is responsible for 500,000 to 1 million deaths annually. And, if diagnosis of HCC doesn’t occur until after the onset of symptoms, the 5-year survival is estimated at 18%.
Liver cancer is almost always a complication of a chronic liver disease called cirrhosis. The leading causes of cirrhosis are excessive and prolonged alcohol consumption, chronic infections with hepatitis B and hepatitis C viruses, and metabolic syndrome (overweight or obesity, diabetes, high blood pressure).
Cannabis is the third most consumed psychoactive substance globally, after alcohol and tobacco. It has recently been considered for clinical applications.
The World Health Organization (WHO) currently estimates that 128 to 232 million people worldwide use it, and the growing legalization of cannabis will likely increase this number.
In recent years, several clinical trials have tested the efficacy of new agents in the fight against liver cancer. Unfortunately, no significant improvement in patient prognosis has been achieved so far.
However, despite its widespread use, the clinical benefits of cannabis have yet to be studied and could perhaps provide a solution to the lack of treatments for certain cancers.
In this context, a team of researchers affiliated with the Cleveland Clinic and Georgetown University Hospital in Washington DC assessed the relationship between cannabis use and HCC in a cohort of over one million subjects. Their data is published in the journal Cureus.
To study the possible relationship between cannabis and liver cancer, the authors selected from the National Inpatient Sample (NIS) database patients with HCC between 2002 and 2014.
Of the 101,231,036 adult NIS patients from 2002 to 2014, researchers identified 996,290 (1%) cannabis-using patients, compared to 100,234,746 (99%) non-cannabis-using patients. The group of cannabis users had a higher prevalence of alcohol abuse, history of smoking, HBV, HCV, and liver cirrhosis, all precursor pathologies of liver cancer. Nevertheless, they had a lower prevalence of HCC, obesity, and gallstones than the non-drinking group.
Additionally, the authors also identified 111,040 (0.1%) HCC patients, of whom 734 (0.7%) were cannabis users. Using multivariate logistic regression and adjusting for patient demographics, comorbidities, and hospital characteristics, they estimated that cannabis users were 55% less likely to develop liver cancer than non-cannabis users.
Cannabis can affect liver cancer through two active chemical compounds, tetrahydrocannabinol (THC) and CBD. Each binds to their respective CB-1 and CB-2 cannabinoid receptors in the body.
In the liver, CB-1 receptor signaling stimulates hepatic stellate cells. This promotes steatohepatitis — a chronic disease with an accumulation of fat in the liver (steatosis) associated with inflammation of the organ (hepatitis) — and liver fibrosis, a scarring process whose ultimate evolution is cirrhosis, a significant complication of many liver diseases.
Conversely, activation of the CB-2 receptor decreases hepatic immune cell infiltration, oxidative stress, liver damage, and fibrogenesis, thus inhibiting liver cirrhosis and ultimately liver cancer.
Some studies on mouse and rat cells have shown that cannabinoids can inhibit tumor growth by causing cancer cell death. This happens as the cannabinoids block cell division by preventing angiogenesis (production of vessels to nourish tumor) 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, particularly CBD, explains the study’s observation that cannabis reduces the occurrence of liver cancer.
In simple terms, cannabis could serve as protection against liver cancer or at least allow a slowing down of the progression of the disease. In addition, the pharmaceutical development of compounds exerting the double effect of CB1 antagonism and CB2 agonism would be a significant advance in managing liver diseases.
The authors conclude, “To our knowledge, this is the first and largest cross-sectional study based on hospitalized patient population to explore the association between cannabis use and HCC. However, due to our study’s cross-sectional design, we cannot draw direct causal effects. Therefore, we suggest prospective clinical studies to understand better the mechanism by which various active ingredients, particularly CBD in cannabis, may regulate the development of hepatocellular carcinoma.”
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(Featured image by Gustavo Fring via Pexels)
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