Liver Disease Information: Liver Disease and Medical Marijuana Treatments
Your liver helps fight infections and cleans your blood. It also helps digest food and stores energy for when you need it. A healthy liver has the amazing ability to grow back, or regenerate, when it is damaged. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis A, hepatitis B and hepatitis C.
There is wealth of new scientific understanding regarding how medical marijuana or cannabis can be beneficial for treating Liver Disease.
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.
Cannabidiol causes activated hepatic stellate cell death through a mechanism of endoplasmic reticulum stress-induced apoptosis.
- Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA.
The major cellular event in the development and progression of liver fibrosis is the activation of hepatic stellate cells (HSCs). Activated HSCs proliferate and produce excess collagen, leading to accumulation of scar matrix and fibrotic liver. As such, the induction of activated HSC death has been proposed as a means to achieve resolution of liver fibrosis. Here we demonstrate that cannabidiol (CBD), a major non-psychoactive component of the plant Cannabis sativa, induces apoptosis in activated HSCs through a cannabinoid receptor-independent mechanism. CBD elicits an endoplasmic reticulum (ER) stress response, characterized by changes in ER morphology and the initiation of RNA-dependent protein kinase-like ER kinase-, activating transcription factor-6-, and inositol-requiring ER-to-nucleus signal kinase-1 (IRE1)-mediated signaling cascades. Furthermore, CBD induces downstream activation of the pro-apoptotic IRE1/ASK1/c-Jun N-terminal kinase pathway, leading to HSC death. Importantly, we show that this mechanism of CBD-induced ER stress-mediated apoptosis is specific to activated HSCs, as it occurs in activated human and rat HSC lines, and in primary in vivo-activated mouse HSCs, but not in quiescent HSCs or primary hepatocytes from rat. Finally, we provide evidence that the elevated basal level of ER stress in activated HSCs has a role in their susceptibility to the pro-apoptotic effect of CBD. We propose that CBD, by selectively inducing death of activated HSCs, represents a potential therapeutic agent for the treatment of liver fibrosis.
Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice.
- Department of Human Nutrition and Metabolism, Braun School of Public Health, Hadassah-Hebrew University Medical School, Jerusalem, Israel. email@example.com
BACKGROUND AND PURPOSE:
Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT(1A) , on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide.
Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure.
Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment.
CONCLUSIONS AND IMPLICATIONS:
Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain.
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
The endocannabinoid system and liver diseases.
- Department of Internal Medicine, Cardioangiology, Hepatology, Alma Mater Studiorum University of Bologna, Bologna, Italy. firstname.lastname@example.org
Endogenous cannabinoids (EC) are ubiquitous lipid signalling molecules provided by a number of central and peripheral effects, which are mainly mediated by the specific cannabinoid receptors CB(1) and CB(2). Although the expression of these receptors is very low or even absent in the healthy liver, a considerable series of experimental studies and some clinical observations have recognised the EC system as an important player in the pathophysiology of liver diseases. The EC system is highly up-regulated during chronic liver diseases and, to date, it has been implicated in the pathogenesis of non-alcoholic fatty liver disease, progression of fibrosis to cirrhosis and the development of the cardiovascular abnormalities of cirrhosis, such as the hyperdynamic circulatory syndrome and cirrhotic cardiomiopathy. Furthermore, the EC system influences the mechanisms responsible for cell damage and the inflammatory response during acute liver injury, such as that resulting from ischaemia-reperfusion. Thus, 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.
Therapeutic potential of cannabidiol against ischemia/reperfusion liver injury in rats.
- Department of Biomedical Sciences, Pharmacology Division, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia.
The therapeutic potential of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated in rats exposed to ischemia/reperfusion liver injury. Ischemia was induced by clamping the pedicle of the left hepatic lobe for 30 min, and cannabidiol (5mg/kg, i.v.) was given 1h following the procedure and every 24h thereafter for 2 days. Ischemia/reperfusion caused significant elevations of serum alanine aminotransferase and hepatic malondialdehyde, tumor necrosis factor-α and nitric oxide levels, associated with significant decrease in hepatic reduced glutathione. Cannabidiol significantly attenuated the deterioration in the measured biochemical parameters mediated by ischemia/reperfusion. Histopathological examination showed that cannabidiol ameliorated ischemia/reperfusion-induced liver damage. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin protein in ischemic/reperfused liver tissue. These results emphasize that cannabidiol represents a potential therapeutic option to protect the liver against hypoxia-reoxygenation injury.