Cannabis and Liver Disease

The human liver is the largest organ in the body.  It has many functions as well as afflictions.  Some are inherited and others are through abuse or viruses.  There are many kinds of liver diseases. Viruses cause some of them, like hepatitis A, hepatitis B and hepatitis C. Others can be the result of drugs, poisons or drinking too much alcohol. If the liver forms scar tissue because of an illness, it’s called cirrhosis.  Jaundice, or yellowing of the skin, can be one sign of liver disease.  Like other parts of your body, cancer can affect the liver. You could also inherit a liver disease such as hemochromatosis.  Below are studies that show the interaction of cannabis compounds and the liver.  Please feel free to share ~ Cherry Girl

The Endocannabinoid System As A Novel Target For the Treatment of Liver Fibrosis
We have recently demonstrated that CB1 and CB2 receptors display opposite effects in the regulation of liver fibrogenesis during chronic liver injury. Indeed, both receptors are up-regulated in the liver of cirrhotic patients, and expressed in liver fibrogenic cells. Moreover, CB1 receptors are profibrogenic and accordingly, the CB1 antagonist rimonabant reduces fibrosis progression in three experimental models. In keeping with these results, daily cannabis smoking is a risk factor for fibrosis progression in patients with chronic hepatitis C. In contrast, CB2 display antifibrogenic effects, by a mechanism involving reduction of liver fibrogenic cell accumulation. These results may offer new perspectives for the treatment of liver fibrosis, combining CB2 agonist and CB1 antagonist therapy.

The Endocannabinoid System and Liver Diseases
The endocannabinoid system and liver diseases… molecules targeting the CB(1) and CB(2) receptors may represent potential therapeutic agents for the treatment of liver diseases. At present, the CB(1) antagonists represent the most attractive pharmaceutical tool to resolve fat accumulation in patients with non-alcoholic fatty liver disease and to treat patients with cirrhosis, as they may slow the progression of fibrosis and attenuate the cardiovascular alterations associated with the advanced stage of the disease.

Endocannabinoids in Liver Disease
Marijuana has been used for its psychoactive and medicinal properties for millennia. As other plant-derived substances, marijuana has been slow to yield its secrets, with insights into its mechanism of action beginning to emerge only during the last decades… Endocannabinoids are lipid mediators of the same cannabinoid (CB) receptors that mediate the effects of marijuana… Although the documented therapeutic potential of CB(1) blockade is limited by neuropsychiatric side effects, these may be mitigated by using novel, peripherally restricted CB(1) antagonists.

Endogenous Cannabinoids in Liver Disease: Many Darts For A Single Target
Endogenous cannabinoids are ubiquitous lipid-signaling molecules able to partially mimic the actions produced by Delta(9)-tetrahydrocannabinol, the compound responsible for most of the effects of marijuana… The endocannabinoid system is involved in the pathogenesis of the cardiovascular dysfunction occurring in advanced liver disease and also plays a role in the pathogenesis of portal hypertension and liver fibrosis… These findings indicate that the endocannabinoid system may open new avenues for the therapeutic regulation of fibrosis and portal hypertension in advanced liver disease.

Cannabinoid Receptors As New Targets of Antifibrosing Strategies During Chronic Liver Diseases
Cannabinoid receptors as new targets of antifibrosing strategies during chronic liver diseases… Chronic liver injury exposes the patient to liver fibrosis and its end stage, cirrhosis, is a major public health problem worldwide… prevailing causes of cirrhosis include chronic alcohol consumption, hepatitis C virus infection and non-alcoholic steatohepatitis…. the authors recently demonstrated that the endocannabinoid system shows promise as a novel target for antifibrotic therapy during chronic liver injury. Indeed, cannabinoid receptors CB1 and CB2 promote dual pro- and antifibrogenic effects, respectively. Therefore, endocannabinoid-based therapies, combining CB2 agonists and CB1 antagonists may open novel therapeutic perspectives for the treatment of chronic liver diseases.

CB1 Cannabinoid Receptor Antagonism: A New Strategy For the Treatment of Liver Fibrosis
Hepatic fibrosis, the common response associated with chronic liver diseases, ultimately leads to cirrhosis, a major public health problem worldwide.  Genetic or pharmacological inactivation of CB1 receptors decreased fibrogenesis by lowering hepatic transforming growth factor (TGF)-beta1 and reducing accumulation of fibrogenic cells in the liver after apoptosis and growth inhibition of hepatic myofibroblasts. In conclusion, our study shows that CB1 receptor antagonists hold promise for the treatment of liver fibrosis.

Role of Cannabinoids in Chronic Liver Diseases
The role of the endocannabinoid system in hepatic physiology and pathologic conditions has been studied recently. Unquestionably, influencing endocannabinoid signaling may have a beneficial effect on delaying or even reversing hepatic fibrosis.

CB2 Receptors As New Therapeutic Targets For Liver Diseases
phytocannabinoids have long been used for recreational and therapeutic purposes… studies have unravelled pleiotropic functions of CB2 receptors under physiological and pathological conditions, including acute and chronic liver diseases. Additional functions may soon arise… These findings may open novel therapeutic avenues, upon clinical development of CB2-specific molecules.

Beneficial Paracrine Effects of Cannabinoid Receptor 2 on Liver Injury and Regeneration
CONCLUSION: CB2 receptors reduce liver injury and promote liver regeneration following acute insult, via distinct paracrine mechanisms involving hepatic myofibroblasts. These results suggest that CB2 agonists display potent hepatoprotective (ability to prevent damage to the liver) properties, in addition to their antifibrogenic effects.

Cannabinoid Receptor Type I Modulates Alcohol-Induced Liver Fibrosis
CB1 expression is upregulated in human ALF (alcoholic liver fibrosis ) which is at least in part triggered by acetaldehyde (AA) and oxidative stress. Inhibition of CB1… or via genetic knock-out protects against alcoholic-induced fibrosis in vitro and in vivo….CB1 antagonists have been used in treating alcohol dependence without causing significant depression.

The Endocannabinoid System As A Key Mediator During Liver Diseases: New Insights and Therapeutic Openings
“The endocannabinoid system as a key mediator during liver diseases: new insights and therapeutic openings… hepatic cannabinoid receptor 2 (CB(2)) receptors display beneficial effects on alcoholic fatty liver, hepatic inflammation, liver injury, regeneration and fibrosis. Cannabinoid receptor 1 (CB(1)) receptors have been implicated in the pathogenesis of several lesions such as alcoholic and metabolic steatosis, liver fibrogenesis, or circulatory failure associated with cirrhosis… data obtained with peripherally restricted CB(1) antagonists give real hopes in the development of active CB(1) molecules devoid of central adverse effects.

Pathogenesis of Alcohol-Induced Liver Disease: Classical Concepts and Recent Advances
Alcoholic liver disease (ALD) is a primary consequence of heavy and prolonged drinking.  The observation that ALD and non-alcoholic steatohepatitis share common pathways and genetic polymorphisms suggests operation of parallel pathogenic mechanisms. Future research involving genomics, epigenomics, deep sequencing and non-coding regulatory elements holds promise to identify novel diagnostic and therapeutic targets for ALD. There is also a need for adequate animal models to study pathogenic mechanisms at the molecular level and targeted therapy.

The Role of the Cannabinoid System in the Pathogenesis and Treatment of Alcohol Dependence
The lack of satisfactory results of alcohol dependence treatment force us to search for new directions of research.  SR141716 (rimonabant), a CB1 receptor antagonist, significantly lowers voluntary alcohol intake and motivation for its consumption in various experimental studies. Very encouraging results of preclinical studies were not completely confirmed in the clinical studies. However, further clinical studies are still necessary.