Cannabis consumption may reduce the pain, prevalence, and burden of hepatic and liver conditions.
Early preclinical and epidemiological research suggests that cannabis may potentially treat various forms of liver disease; even that caused by pain pills. Liver disease is an umbrella term for conditions that result in a disturbance of liver function. The causes are widespread, consequently including drugs and alcohol, hepatitis A-E, non-alcoholic fatty liver disease, and hemochromatosis. In essence, when the liver is repeatedly damaged, scar tissue replaces healthy liver cells in a process called fibrosis. This scar tissue does not perform any function, further distorting the liver’s internal structure, and interfering with blood flow to and from the liver. It may even cause liver pain.
Eventually, this lack of blood flow kills more liver cells and the result is a continuous cycle of liver scarring. Doctors often focus on the cause of liver disease, for example, alcohol or prescribing antiviral drugs, but in all cases, slowing or preventing fibrosis is the key. Research suggests that cannabis may have anti-fibrogenic properties. Consequently, in epidemiological studies, cannabis consumers have a lower prevalence of liver disease progression than their peers. Could cannabis effectively treat liver disease, like it does pain, nausea, and so many other conditions?
CBD and Hepatic Stellate Cell Death
Basically, the cellular mechanisms at work for the development of liver fibrosis chiefly involve specialized cells called hepatic stellate cells (HSC).Zhang, C. Y., Yuan, W. G., He, P., Lei, J. H., & Wang, C. X. (2016). Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets. World Journal of … Continue reading HSCs play a critical role in the initiation, progression, and regression of liver fibrosis, by secreting fibrogenic factors that encourage other cells to produce collagen and corresponding scar tissue. Consequently, researchers have proposed that activating HSC death could be a solution for reducing liver fibrosis.
In a study published in Cell Death and Disease (2011), the researchers investigated whether CBD could activate and kill HSCs.Lim, M. P., Devi, L. A., & Rozenfeld, R. (2011). Cannabidiol causes activated hepatic stellate cell death through a mechanism of endoplasmic reticulum stress-induced apoptosis. Cell Death & … Continue reading because of this study, researchers know that CBD induces apoptosis in HSCs through a cannabinoid receptor-independent mechanism involving an endoplasmic reticulum stress response and downstream apoptotic pathways. HSC death occurred in both human and rat cell lines, as well as in vivo mouse HSCs. They concluded that CBD may provide therapeutic benefit for liver fibrosis. Other researchers have found success by directly and purposefully targeting the CB2 receptor.
Fibrosis Regression Following Chronic CB2 Receptor Activation
In a study published in the Journal of Pharmacology and Experimental Therapeutics (2007), the researchers would chronically activate hepatic CB2 receptors in cirrhotic rats. They did so by treating them with a CB2 receptor agonist daily, for a total of nine days. Muñoz-Luque, J., Ros, J., Fernández-Varo, G., Tugues, S., Morales-Ruiz, M., Alvarez, C. E., … & Jiménez, W. (2008). Regression of fibrosis after chronic stimulation of cannabinoid CB2 … Continue reading
All in all, after treatment, arterial pressure improved, activated stellate cells decreased, and there was also a reduction in fibrosis compared to rats treated without the CB2 receptor agonist. These findings suggest that selective activation of liver CB2 receptors significantly reduces collagen build-up in cirrhotic rats and presents as a possible future treatment for hepatic fibrosis in human cirrhosis.
Further studies will explore how these findings relate to naturally occurring cannabinoids like THC and CBD, but it is clear that an association exists between endocannabinoid system activation and a reduction in hepatic fibrosis. Although clinical trials have not been conducted yet, there is some research to suggest that this may be the case in humans.
Reduced Liver Disease and Pain for Cannabis Consumers?
Epidemiological studies have consistently found a lower prevalence of advanced liver disease among cannabis consumers compared to their non-cannabis consuming counterparts. Further, this is true of alcoholic liver disease, non-alcoholic fatty liver disease, and liver disease caused by chronic Hepatitis C viral infection.
Moreover, in a study published in Liver International (2018), the researchers analyzed the discharge records of patients eighteen years and older who reported past or current history of alcohol abuse.Adejumo, A. C., Ajayi, T. O., Adegbala, O. M., Adejumo, K. L., Alliu, S., Akinjero, A. M., … & Bukong, T. N. (2018). Cannabis use is associated with reduced prevalence of progressive stages … Continue reading In total, they analyzed over 300,000 records from the 2014 Healthcare Cost and Utilization Project-Nationwide Inpatient Sample and studied progressive alcohol liver disease with respect to three cannabis exposure groups: non-cannabis consumers, non-dependent cannabis consumers, and dependent cannabis consumers. Basically, the results showed that among alcohol users, dependent and non-dependent cannabis consumers had significantly lower odds of developing alcoholic steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. Furthermore, dependent cannabis consumers were slightly less likely to develop liver disease compared to non-dependent consumers.
Do Cannabis Consumers Have Less Liver Disease and Pain?
A similar study published in PLoS One (2017), used data from the same 2014 project and accordingly identified the same three cannabis exposure groups.Adejumo, A. C., Alliu, S., Ajayi, T. O., Adejumo, K. L., Adegbala, O. M., Onyeakusi, N. E., … & Bukong, T. N. (2017). Cannabis Use associates with reduced prevalence of non-alcoholic fatty … Continue reading However, the researchers focused on non-alcoholic fatty liver disease. They found that across a sample of almost six million patients, cannabis consumers had a significantly lower prevalence of non-alcoholic fatty liver disease compared to non-consumers. Basically, the prevalence of non-alcoholic fatty liver disease was fifteen percent lower for non-dependent consumers, and fifty-two percent lower for dependent consumers.
Finally, researchers found the same trends for liver disease caused by Hepatitis C viral infection (HCV). In a study published in the Canadian Journal of Gastroenterology and Hepatology (2018), the researchers found that cannabis-consuming HCV patients were less likely to develop liver disease and had lower healthcare costs than non-consumers, comparatively. Adejumo, A. C., Adegbala, O. M., Adejumo, K. L., & Bukong, T. N. (2018). Reduced incidence and better liver disease outcomes among chronic HCV infected patients who consume cannabis. Canadian … Continue reading However, there was no difference between these two groups regarding the incidence of liver carcinoma or in-hospital mortality.
Strong Rationale for Future Clinical Trials
The Canadian Association of Gastroenterology recently stated that, “Although cannabinoids have been associated with improved outcomes in nonalcoholic fatty liver disease and alcoholic fatty liver disease in epidemiological studies, there is insufficient data to support their use in these diseases.”Andrews, C. N., Devlin, S. M., Le Foll, B., Fischer, B., Tse, F., Storr, M., & Congly, S. E. (2019). Canadian association of gastroenterology position statement: use of cannabis in … Continue reading
However, don’t be alarmed. This does not mean that there is evidence that cannabis doesn’t work. Basically, it means the science hasn’t got there yet. The combination of successful preclinical evidence and encouraging prevalence data makes further clinical trials investigating cannabinoids for the treatment of liver disease inevitable. Accordingly, researchers will be conducting clinical trials in the future.
In due time, the results may show that there is a ‘new’ therapeutic to help prevent nearly two million deaths per year from liver disease, on top of pain, drug addiction, nausea, and the other conditions cannabis may help with.Asrani, S. K., Devarbhavi, H., Eaton, J., & Kamath, P. S. (2019). Burden of liver diseases in the world. Journal of Hepatology, 70(1), 151-171.
|↑1||Zhang, C. Y., Yuan, W. G., He, P., Lei, J. H., & Wang, C. X. (2016). Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets. World Journal of Gastroenterology, 22(48), 10512.|
|↑2||Lim, M. P., Devi, L. A., & Rozenfeld, R. (2011). Cannabidiol causes activated hepatic stellate cell death through a mechanism of endoplasmic reticulum stress-induced apoptosis. Cell Death & Disease, 2(6), e170-e170.|
|↑3||Muñoz-Luque, J., Ros, J., Fernández-Varo, G., Tugues, S., Morales-Ruiz, M., Alvarez, C. E., … & Jiménez, W. (2008). Regression of fibrosis after chronic stimulation of cannabinoid CB2 receptor in cirrhotic rats. Journal of Pharmacology and Experimental Therapeutics, 324(2), 475-483.|
|↑4||Adejumo, A. C., Ajayi, T. O., Adegbala, O. M., Adejumo, K. L., Alliu, S., Akinjero, A. M., … & Bukong, T. N. (2018). Cannabis use is associated with reduced prevalence of progressive stages of alcoholic liver disease. Liver International, 38(8), 1475-1486.|
|↑5||Adejumo, A. C., Alliu, S., Ajayi, T. O., Adejumo, K. L., Adegbala, O. M., Onyeakusi, N. E., … & Bukong, T. N. (2017). Cannabis Use associates with reduced prevalence of non-alcoholic fatty liver disease: A cross-sectional study. PLoS One, 12(4), e0176416.|
|↑6||Adejumo, A. C., Adegbala, O. M., Adejumo, K. L., & Bukong, T. N. (2018). Reduced incidence and better liver disease outcomes among chronic HCV infected patients who consume cannabis. Canadian Journal of Gastroenterology and Hepatology, 2018.|
|↑7||Andrews, C. N., Devlin, S. M., Le Foll, B., Fischer, B., Tse, F., Storr, M., & Congly, S. E. (2019). Canadian association of gastroenterology position statement: use of cannabis in gastroenterological and hepatic disorders. Journal of the Canadian Association of Gastroenterology, 2(1), 37.|
|↑8||Asrani, S. K., Devarbhavi, H., Eaton, J., & Kamath, P. S. (2019). Burden of liver diseases in the world. Journal of Hepatology, 70(1), 151-171.|