Does Marijuana Help or Hurt Cirrhosis?

Overview of Cirrhosis

Cirrhosis is the late stage of scarring, or fibrosis, of the liver. It can be caused by a variety of conditions, including hepatitis and chronic alcohol abuse. The scarring associated with cirrhosis develops in response to damage done to the liver and it cannot be undone. The liver is responsible for detoxifying harmful substances within your body and cleaning your blood and making vital nutrients, but the scarring that develops makes it difficult for the liver to function properly. When cirrhosis is advanced, it can be life threatening. If diagnosed and treated early, however, further damage can be limited and prevented.

According to Mayo Clinic, some causes of cirrhosis are inherited, like iron buildup, cystic fibrosis, and genetic digestive disorder, while other causes occur later in life, like chronic alcohol abuse, hepatitis c, hepatitis b and nonalcoholic fatty liver disease.

Patients with cirrhosis commonly experience fatigue, easy bleeding and bruising, itchy skin, loss of appetite and nausea, leg swelling, weight loss, fluid accumulation in the abdomen, and red spider-like blood vessels on the skin.

Treatment for cirrhosis is dictated by the extent of the liver damage upon diagnosis. The goals are to slow further scar tissue progression and prevent or treat associated symptoms. In some cases, if a liver ceases to function, a liver transplant may be required.

Findings: Effects of Cannabis on Cirrhosis

Research regarding cannabis and its potential impact on cirrhosis and other chronic liver diseases is complex. The two major cannabinoids found in cannabis, tetrahydrocannabinol (THC) and cannabidiol (CBD) bind with or influence the cannabinoid receptors (CB1 and CB2) of the endocannabinoid system within the body. Previous studies had actually implicated action of CB1 in the progression of cirrhosis, fibrosis, and other liver diseases. However, CB2 receptor activation has shown beneficial effects on alcoholic fatty liver, hepatic inflammation, liver injury, regeneration and fibrosis and CBD has. Therefore, research suggests that using cannabis to selectively activate the CB2 receptor offers therapeutic potential for cirrhosis and other liver diseases (Mallat, et al., 2011).

Studies suggest that CBD can help combat cirrhosis progression by assisting in the death of hepatic stellate cells (HSCs). When HSCs are activated, they proliferate and produce excess collagen, which causes 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). Cannabidiol has also been shown to restore liver function in mice experiencing liver failure (Abraham, et al., 2011).

Findings also support that CBD can serve as a protective strategy against ischemia reperfusion, the pivotal mechanism of tissue damage in cirrhosis, by reducing the force of key inflammatory pathways and oxidative/nitrative tissue injury. These effects of CBD are independent of their impact on the CB2 receptors (Mukhopadhyay, Rajesh & Pacher, 2011).

CBD has also proven effective at protecting the liver from steatosis caused by alcohol drinking by preventing an increase in oxidative stress and the autophagy induced by alcohol, thus protecting the liver from progressive damage (Yang, et al., 2014).

Cannabis may also serve helpful in managing symptoms associated with cirrhosis. Cannabis has long been known to limit or prevent nausea and vomiting from a variety of causes (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).

States That Have Approved Medical Marijuana for Cirrhosis

No states have approved medical marijuana specifically for the treatment of cirrhosis. However, states have approved cannabis to treat some symptoms commonly associated with cirrhosis.

Currently, 17 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.

In addition, for those cirrhosis patients also experiencing extreme weight loss or cachexia, 20 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.

A number of other states will consider allowing medical marijuana to be used for the treatment of cirrhosis with recommendation by 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”).

In Washington D.C., any condition can be approved for medical marijuana as long as a DC-licensed physician recommends the treatment.

Recent Studies on Cannabis’ Effect on Cirrhosis

• CBD shown to kill the hepatic stellate cells that are responsible for the accumulation of scarring on the liver.
  Cannabidiol causes activated hepatic stellate cell death through a mechanism of endoplasmic reticulum stress-induced apoptosis.
  (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168994/)

• Cannabidiol was able to restore normal liver function in mice experiencing liver failure.
  Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice.
  (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057300/)

References:

1. Avraham, Y., Grigoriadis, N., Poutahidis, T., Vorobiev, L., Magen, I., Ilan, Y., Mechoulam, R., and Berry, E. (2011, April). Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice. British Journal of Pharmacology, 162(7), 1650-8. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057300/.
2. 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. Retrieved from http://goo.gl/WJvaxy.
3. (2014, August 16). Mayo Clinic. Retrieved from http://www.mayoclinic.org/diseases-conditions/cirrhosis/basics/definition/con-20031617.
4. (2014, November 20). MedlinePlus. Retrieved from https://www.nlm.nih.gov/medlineplus/ency/article/000255.htm.
5. 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/.
6. 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. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165953/.
7. 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. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081988/.
8. 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. Retrieved from http://onlinelibrary.wiley.com/wol1/doi/10.1002/cpt.98/full.
9. Sharkey, KA., Darmani, NA., and Parker, LA. (2014). Regulation of nausea and vomiting by cannabinoids and the endocannabinoid system. European Journal of Pharmacology, 722, 134-46. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883513/.
10. Yang, L., Rozenfeld, R., Wu, D., Devi, LA., 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. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112960/.