Liver Disorders and Cannabidiol

Liver Disorders – Medical Marijuana Research Overview

11 December, 2015
The following information is presented for educational purposes only. Medical Marijuana Inc. provides this information to provide an understanding of the potential applications of cannabidiol. Links to third party websites do not constitute an endorsement of these organizations by Medical Marijuana Inc. and none should be inferred.

Damage to the liver can cause a variety of disorders that can lead to the organ’s failure and potentially threaten one’s life. Studies have shown cannabis encourages liver health and can protect it from damage.

Overview of Liver Disorders

There are many different types of disorders and diseases that can affect the liver, which is an organ responsible for digesting food and ridding the body of toxic substances. The disorders can be inherited or caused by lifestyle and health factors, like alcohol abuse and viruses, which damage the liver. In addition, obesity can cause damage to the liver.

The symptoms associated with liver disorders can include swelling and pain in the abdomen, yellowish skin and eyes, itchy skin, dark urine, pale stool, chronic fatigue, nausea and vomiting, loss of appetite and a tendency to bruise easily.

The most common types of liver disorders include:

Hepatitis – A virus or parasite that causes inflammation of the liver and a reduction in its function. Hepatitis A causes acute inflammation of the liver and will commonly get better without treatment. Hepatitis B can be acute and chronic and it spreads through blood and other body fluids. Hepatitis C is nearly always chronic and spreads through blood.

Cirrhosis – The immune system mistakenly attacks healthy cells in the liver, causing the formation of a fibrous tissue, or scarring, that replaces dead cells.

Non-alcoholic Fatty Liver Disease – The build-up of extra fat in the cells of the liver and due to causes other than alcohol consumption.

Haemochromatosis – In haemochromatosis, the liver becomes damaged from the build up of iron. An abnormal gene inherited by one or both parents causes the disease.

Wilson’s Disease – Rare and inherited, Wilson’s disease is caused by too much copper accumulating the liver, brain and other organs.

Cancer of the Liver – Primary liver cancer, or hepatocellular carcinoma, typically develops in livers that are damaged by alcohol abuse, hepatitis, hemochromatosis or birth defects.

Primary Schlerosing Cholangitis – A disease of the liver’s bile ducts, which are responsible for carrying bile to the small intestine for digestion. In the disorder, inflammation causes scars to develop within the bile ducts.

Primary Biliary Cirrhosis – The immune system mistakenly destroys the bile ducts of the liver.

Budd-Chiari Syndrome – An uncommon condition characterized by the occlusion of the hepatic veins, which obstructs the outflow of blood.

The treatment of liver disorders depends on the type of disease. Typically, the cessation of alcohol use and a reduction in body weight is necessary. Many cases of liver disorders may require medications or surgery.

Findings: Effects of Cannabis on Liver Disorders

Research has shown that cannabidiol (CBD), a major cannabinoid found in cannabis that activates the CB2 receptors of the body’s endocannabinoid system, is therapeutically beneficial for treating many liver disorders (Mallat, et al., 2011).

Studies have shown that CBD can help combat cirrhosis by assisting in the death of hepatic stellate cells (HSCs), which are responsible for the accumulation of scarring on the liver. CBD’s activation of the CB2 receptors, however, has been shown to be effective at inducing apoptosis (death) in these activated HSCs (Lim, Devi & Rozenfeld, 2011). Research also shows it reduces the force of inflammatory pathways and oxidative tissue injury, therefore limiting the damage caused by cirrhosis (Mukhopadhyay, Rajesh & Pacher, 2011).

CBD has also shown to possess liver protective properties and to promote liver health. CBD was shown to prevent oxidative stress and autophagy from alcohol consumption (Yang, et al., 2014). One study found that cannabinoids inhibited CYP1A enzymatic activity, meaning it reduced the liver’s risk of toxicity and cancer (Ashino, Hakukawa, Itoh & Numazawa, 2014). An animal study found that CBD was effective at restoring liver function in mice with liver failure (Avraham, et al, 2011).

Research also suggests that cannabis’ anti-inflammatory and protective properties help in the treatment of hepatitis. One study found that cannabinoids’ anti-inflammatory properties effectively reduced inflammation of a damaged liver and researchers therefore suggested that cannabis could be developed as a potential drug for hepatitis (Lavon, et al., 2003). Another study found that cannabinoids appeared have immunosuppressive and profibrogenic effects in patients with chronic hepatitis C (Patsenker, et al., 2015).

Cannabis can also be helpful in managing symptoms associated with cirrhosis, hepatitis C and other liver disorders. Cannabis has long been established as effective for limiting nausea and vomiting, including patients with hepatitis C who can become sick following antiviral treatment (Schnelle, Grotenhermen, Reif & Gorter, 1999) (Sharkey, Darmani & Parker, 2014) (Parker, et al., 2015). In addition, if cirrhosis patients are suffering from a loss of appetite, medical marijuana has demonstrated effective at increasing appetite and stabilizing body weight (Beal, et al., 1995). Cannabis use was found to significantly affect whether patients with hepatitis C were able to stick with their treatment prescription (Sylvestre, Clements & Malibu, 2006).

Recent animal studies suggest that CBD may inhibit the progression of cancer (McAllister, Soroceanu & Desprez, 2015) (Orellana-Serradell, et al., 2015) (Ligresti, et al., 2006). CBD acid (CBDA) was shown to down-regulate invasive human brain cancer cells and prevent their growth (Takeda, et al., 2014).

It’s important to note that earlier studies implicated cannabis in the progression of cirrhosis, fibrosis, and other liver diseases (Fischer, et al., 2006). However, more recent research has determined that marijuana smoking is not linked to the development or progression of liver disease (Brunet, et al., 2013). In addition, the earlier studies had actually found liver disease to be associated with activation of the CB1 receptor. Activation of the CB2 receptor, however, has shown to have beneficial effects on alcoholic fatty liver, hepatic inflammation, liver injury, regeneration and fibrosis. This suggests that using cannabis to selectively activate the CB2 receptor offers therapeutic potential for cirrhosis and other liver diseases (Mallat, et al., 2011). Further, researchers have expressed that cannabis’ potential treatment benefits outweigh the risks suggested in earlier studies (Fischer, et al., 2006).

States That Have Approved Medical Marijuana for Liver Disorders

Currently, 12 states have approved medical marijuana specifically for the treatment of hepatitis C. These states include: Arizona, Arkansas, Illinois, Maine, Massachusetts, Michigan, New Hampshire, New Mexico, North Dakota, Ohio, Rhode Island and Washington.

In addition, nearly all states that have passed medical marijuana legislation have approved medical marijuana specifically for the treatment of cancer. These states include:  Alaska, Arkansas, Arizona, California, Colorado, Connecticut, Delaware,Florida, Georgia, Hawaii, Illinois, Louisiana, Maine, Massachusetts, Michigan, Minnesota, Montana, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Dakota, Ohio, Oregon, Pennsylvania, Rhode Island, Vermont andWashington.

No states have approved medical marijuana specifically for the treatment of cirrhosis, non-alcoholic fatty liver disease, haemochromatosis, Wilson’s disease, primary schlerosing cholangitis, or primary biliary cirrhosis.

However, in Washington D.C., any condition can be approved for medical marijuana as long as a DC-licensed physician recommends the treatment. In addition, a number of other states will consider allowing medical marijuana to be used for the treatment of liver disorders with the recommendation from a physician. These states include: California (any debilitating illness where the medical use of marijuana has been recommended by a physician), Connecticut (other medical conditions may be approved by the Department of Consumer Protection), Massachusetts (other conditions as determined in writing by a qualifying patient’s physician), Nevada (other conditions subject to approval), Oregon (other conditions subject to approval), Rhode Island (other conditions subject to approval), and Washington (any “terminal or debilitating condition”).

Also, various states have approved medical marijuana for the treatment of symptoms commonly associated with liver disorders. For example, 19 states have approved medical marijuana specifically for the treatment of nausea. These states include: Alaska, Arizona, Arkansas, California, Colorado, Delaware, Hawaii, Maine, Maryland, Michigan, Montana, Nevada, New Hampshire, New Mexico, North Dakota, Oregon, Rhode Island, Vermont, and Washington. For patients also experiencing extreme weight loss or cachexia, 23 states have approved medical marijuana for treatment. These states include: Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Hawaii, Illinois, Louisiana, Maine, Maryland, Michigan, Minnesota, Montana, Nevada, New Hampshire, New Mexico, North Dakota, Oregon, Rhode Island, Vermont and Washington. Several states have approved medical marijuana specifically to treat “chronic pain.” These states include: Alaska, Arizona, California, Colorado, Delaware, Hawaii, Maine, Maryland, Michigan, Montana, New Mexico, Ohio, Oregon, Pennsylvania, Rhode Island and Vermont. The states of Nevada, New Hampshire, North Dakota, Montana, Ohio and Vermont allow medical marijuana to treat “severe pain.” The states of Arkansas, Minnesota, Ohio, Pennsylvania and Washington have approved cannabis for the treatment of “intractable pain.”

Recent Studies on Cannabis’ Effect on Liver Disorders

References

Ashino, T., Hakukawa, K., Itoh, Y., and Numazawa, S. (2014). Inhibitory effect of synthetic cannabinoids on CYP1A activity in mouse liver microsomes. The Journal of Toxicological Sciences, 39(6), 815-20.

Avraham, Y., Grigoriadis, N., Poutahidis, T., Vorobiev, L., Magen, I., Ilan, Y., Mechoulam, R., and Berry, E. (2011). Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice. British Journal of Pharmacology, 162(7), 1650–1658.

Beal, J.E., Olson, R., Laubenstein, L., Morales, J.O., Bellman, P., Yangco, B., Lefkowitz, L, Plasse, T.F. and Shephard, K.V. (1995, February). Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. Journal of Pain and System Management, 10(2), 89-97.

Fisher, B., Reimer, J., Firestone, M., Kalousek, K., Rehm, J., and Heathcote, J. (2006, October). Treatment for hepatitis C virus and cannabis use in illicit drug user patients: implications and questions. European Journal of Gastroenterology & Hepatology, 18(10), 1039-42.

Lavon, I., Sheinin, T., Meilin, S., Biton, E., Weksler, A., Efroni, G., Bar-Joseph, A., Fink, G., and Avraham, A. (2003, December). A novel synthetic cannabinoid derivative inhibits inflammatory liver damage via negative cytokine regulation. Molecular Pharmacology, 64(6), 1334-41.

Ligresti, A., Moriello, A.S., Starowicz, K., Matias, I., Pisanti, S., De Petrocellis, L., Laezza, C., Portella, G., Bifulco, M., and Di Marzo, V. (2006, September). Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. Journal of Pharacologogy and Experimental Therapeutics, 318(3), 1375-87.

Lim, M.P., Devi, L.A., and Rozenfeld, R. (2011). Cannabidiol causes activated hepatic stellate cell death through a mechanism of endoplasmic reticulum stress-induced apoptosis. Cell Death & Disease. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168994/.

Liver disease. (2014, July 15). Mayo Clinic. Retrieved from http://www.mayoclinic.org/diseases-conditions/liver-disease/basics/definition/CON-20025300?p=1.

Mallat, A., Teixeira-Clerc, F., Deveaux, V., Manin, S., and Lotersztajn, S. (2011, August). The endocannabinoid system as a key mediator during liver diseases: new insights and therapeutic openings. British Journal of Pharmacology, 163(7), 1432-40.

McAllister, S.D., Soroceanu, L., and Desprez, P.Y. (2015, June). The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids. Journal of Neuroimmune Pharmacology, 10(2), 255-67.

Mukhopadhyay, P., Monanraj, R., and Pacher, P. (2011, May 15). Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death. Free Radical Biology & Medicine, 50(10), 1368-1381.

Orellana-Serradell, O., Poblete, C.E., Sanchez, C., Castellon, E.A., Gallegos, I., Huidobro, C., Llanos, M.N., and Contreras, H.R. (2015, April). Proapoptotic effect of endocannabinoids in prostate cancer cells. Oncology Reports, 33(4), 1599-608.

Parker, L.A., Rock, E.M., Sticht, M.A., Wills, K.L., and Limebeer, C.L. (2015). Cannabinoids suppress acute and anticipatory nausea in preclinical rat models of conditioned gaping. Clinical Pharmacology and Therapeutics, 97(6), 559-61.

Patsenker, E., Sachse, P., Chicca, A., Gachet, M. S., Schneider, V., Mattsson, J., Lanz, C., Worni, M., de Gottardi, A., Semmo, M., Hampe, J., Schafmayer, C., Brenneisen, R., Gertsch, J., Stickel, F., and Semmo, N. (2015). Elevated Levels of Endocannabinoids in Chronic Hepatitis C May Modulate Cellular Immune Response and Hepatic Stellate Cell Activation. International Journal of Molecular Sciences, 16(4), 7057–7076.

Schnelle, M., Grotenhermen, F., Reif, M., and Gorter, R.W. (1999, October). Results of a standardized survey on the medical use of cannabis products in the German-speaking area. Forschende Komplementarmedizin, 3, 28-36.

Sharkey, K.A., Darmani, N.A., and Parker, L.A. (2014). Regulation of nausea and vomiting by cannabinoids and the endocannabinoid system. European Journal of Pharmacology, 722, 134-46.

Sylvestre, D.L., Clements, B.J., and Malibu, Y. (2006, October). Cannabis use improves retention and virological outcomes in patients treated for hepatitis C. European Journal of Gastroenterology & Hepatology, 18(10), 1057-63.

Takeda, S., Okazaki, H., Ikeda, E., Abe, S., Yoshioka, Y, Watanabe, K., and Aramaki, H. (2014). Down-regulation of cyclooxygenase-2 (COX-2) by cannabidiolic acid in human breast cancer cells. The Journal of Toxicological Sciences, 39(5), 711-6.

Yang, L., Rozenfeld, R., Wu, D., Devi, L.A., Zhang, Z., and Cederbaum, A. (2014, March). Cannabidiol protects liver from binge alcohol-induced steatosis by mechanisms including inhibition of oxidative stress and increase in autophagy. Free Radical Biology & Medicine, 68, 260-7.

Zamora-Valdes, D., Ponciano-Rodriguez, G., Chavez-Tapia, N.C., Mendez-Sanchez, N. (2005). The endocannabinoid system in chronic liver disease. Annals of Hepatology, 4(4), 248-254.

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