Emerging role of cannabinoids in gastrointestinal and liver diseases: basic and clinical aspects.

Posted on February 19, 2015 by David

“A multitude of physiological effects and putative pathophysiological roles have been proposed for the endogenous cannabinoid system in the gastrointestinal tract, liver and pancreas.

These range from effects on epithelial growth and regeneration, immune function, motor function, appetite control, fibrogenesis and secretion.

Cannabinoids have the potential for therapeutic application in gut and liver diseases.

Two exciting therapeutic applications in the area of reversing hepatic fibrosis as well as antineoplastic effects may have a significant impact in these diseases.

This review critically appraises the experimental and clinical evidence supporting the clinical application of cannabinoid receptor-based drugs in gastrointestinal, liver and pancreatic diseases.

Application of modern pharmacological principles will most probably expand the selective modulation of the cannabinoid system peripherally in humans.

We anticipate that, in addition to the approval in several countries of the CB(1) antagonist, rimonabant, for the treatment of obesity and associated metabolic dysfunctions, other cannabinoid modulators are likely to have an impact on human disease in the future, including hepatic fibrosis and neoplasia.”

http://www.ncbi.nlm.nih.gov/pubmed/18397936

http://www.thctotalhealthcare.com/category/liver-disease/

Beneficial paracrine effects of cannabinoid receptor 2 on liver injury and regeneration.

Posted on February 19, 2015 by David

“Accumulating data indicate that the cannabinoid system is a crucial mediator in the pathogenesis of a variety of liver diseases.

In the present study we show that CB2 receptors reduce liver injury and accelerate liver regeneration via distinct pathways.

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 properties, in addition to their antifibrogenic effects.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246453/
“Association of the cannabinoid receptor 2 (CB2) Gln63Arg polymorphism with indices of liver damage in obese children: an alternative way to highlight the CB2 hepatoprotective properties.” http://www.ncbi.nlm.nih.gov/pubmed/21608006

http://www.thctotalhealthcare.com/category/liver-disease/

Hyperactivation of anandamide synthesis and regulation of cell-cycle progression via cannabinoid type 1 (CB1) receptors in the regenerating liver.

Posted on February 19, 2015 by David

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“The mammalian liver regenerates upon tissue loss, which induces quiescent hepatocytes to enter the cell cycle and undergo limited replication under the control of multiple hormones, growth factors, and cytokines.

Endocannabinoids acting via cannabinoid type 1 receptors (CB(1)R) promote neural progenitor cell proliferation, and in the liver they promote lipogenesis.

These findings suggest the involvement of CB(1)R in the control of liver regeneration…

We conclude that activation of hepatic CB(1)R by newly synthesized anandamide promotes liver regeneration by controlling the expression of cell-cycle regulators that drive M phase progression.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076854/

http://www.thctotalhealthcare.com/category/liver-disease/

Anandamide Drives Cell Cycle Progression through CB1 Receptors in a Rat Model of Synchronized Liver Regeneration.

Posted on February 18, 2015 by David

“The endocannabinoid system, through cannabinoid receptor signaling by endocannabinoids, is involved in a wide range of functions and physiopathological conditions.

… liver regeneration, a useful in vivo model of synchronized cell proliferation, is characterized by a peak of anandamide that elicits through CB1 receptor the expression of critical mitosis genes. The aim of this study was to focus on the timing of endocannabinoid signaling changes during the different phases of the cell cycle, exploiting the rat liver regeneration model following partial hepatectomy…

These results support the notion that the signaling mediated by anandamide through CB1 receptor may be important for the entry and progression of cells into the cell cycle and hence for their proliferation under mitogenic signals.”

http://www.ncbi.nlm.nih.gov/pubmed/25684344

http://www.thctotalhealthcare.com/category/liver-disease/

Protective and therapeutic effects of cannabis plant extract on liver cancer induced by dimethylnitrosamine in mice

Posted on February 17, 2015 by David

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“Hepatocellular carcinomas will emerge as a major form of malignancy in the coming decades.

When these tumors are in advanced stages, few therapeutic options are available.

Therefore, it is essential to search for new treatment modalities to fight this disease.

Aim

Evaluate the possible protective and therapeutic effects of Cannabis extract on dimethylnitrosamine (DMNA)-induced hepatocarcinogenicity in mice.

Conclusion

The protective effect of cannabis extract is more pronounced in group taking cannabis before DMNA.

Cannabinoids might exert their anti-tumor effects by the direct induction of apoptosis and can decrease telomerase activity by inhibiting the expression of the TERT gene…”

http://www.sciencedirect.com/science/article/pii/S209050681400027X

http://www.thctotalhealthcare.com/category/liver-cancer-2/

Two non-psychoactive cannabinoids reduce intra-cellular lipid levels and inhibit hepatosteatosis.

Posted on January 18, 2015 by David

“Obesity and associated metabolic syndrome have quickly become a pandemic and a major detriment to human health globally.

The presence of non-alcoholic fatty liver disease (NAFLD; hepatosteatosis) in obesity has been linked to the worsening of the metabolic syndrome, including the development of insulin resistance and cardiovascular disease. Currently, there are few options to treat NAFLD, including life style changes and insulin sensitizers.

Recent evidence suggests that the cannabinoids Δ9-tetrahydrocannabivarin (THCV) and cannabidiol (CBD) improve insulin sensitivity; we aimed at studying their effects on lipid levels…

THCV and CBD directly reduce accumulated lipid levels in vitro in a hepatosteatosis model and adipocytes.

…these cannabinoids are able to increase yolk lipid mobilization and inhibit the development of hepatosteatosis respectively.

CONCLUSIONS:

Our results suggest that THCV and CBD might be used as new therapeutic agents for the pharmacological treatment of obesity- and metabolic syndrome-related NAFLD/hepatosteatosis.”

http://www.ncbi.nlm.nih.gov/pubmed/25595882

http://www.thctotalhealthcare.com/category/obesity-2/

Attenuation of experimental autoimmune hepatitis by exogenous and endogenous cannabinoids: involvement of regulatory T cells.

Posted on June 9, 2014 by David

Fig. 1

“Immune-mediated liver diseases including autoimmune and viral hepatitis are a major health problem worldwide. Natural cannabinoids such as Delta(9)-tetrahydrocannabinol (THC) effectively modulate immune cell function, and they have shown therapeutic potential in treating inflammatory diseases.

We investigated the effects of THC in a murine model of concanavalin A (ConA)-induced hepatitis…

Our data demonstrate that targeting cannabinoid receptors using exogenous or endogenous cannabinoids and use of FAAH inhibitors may constitute novel therapeutic modalities to treat immune-mediated liver inflammation.

δ-9-Tetrahydrocannabinol (THC), the major psychoactive component of marijuana (Cannabis sativa), has wide-ranging pharmacological properties. The cannabinoid compounds possess significant immunosuppressive and anti-inflammatory properties. THC and cannabinoid receptor agonists have shown promise in several models of inflammation.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828293/

Role of Myeloid-Derived Suppressor Cells in Amelioration of Experimental Autoimmune Hepatitis Following Activation of TRPV1 Receptors by Cannabidiol

Posted on June 9, 2014 by David

“Myeloid-derived suppressor cells (MDSCs) are getting increased attention as one of the main regulatory cells of the immune system. They are induced at sites of inflammation and can potently suppress T cell functions. In the current study, we demonstrate how activation of TRPV1 vanilloid receptors can trigger MDSCs, which in turn, can inhibit inflammation and hepatitis…

This study demonstrates for the first time that MDSCs play a critical role in attenuating acute inflammation in the liver, and that agents such as CBD, which trigger MDSCs through activation of TRPV1 vanilloid receptors may constitute a novel therapeutic modality to treat inflammatory diseases.

Cannabidiol (CBD) is a major non-psychoactive cannabinoid component of marijuana.

Together, these studies not only demonstrate that CBD can protect the host from acute liver injury but also provide evidence for the first time that MDSCs may play a critical role in protecting the liver from acute inflammation.

Non-psychoactive cannabinoids such as CBD possess great therapeutic potential in treating various inflammatory liver diseases, including autoimmune hepatitis.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069975/

A biosynthetic pathway for anandamide

Posted on June 9, 2014 by David

“The endocannabinoid arachidonoyl ethanolamine (anandamide) is a lipid transmitter synthesized and released “on demand” by neurons in the brain. Anandamide is also generated by macrophages where its endotoxin (LPS)-induced synthesis has been implicated in the hypotension of septic shock and advanced liver cirrhosis. Anandamide can be generated from its membrane precursor, N-arachidonoyl phosphatidylethanolamine (NAPE) through cleavage by a phospholipase D (NAPE-PLD).

Here we document a biosynthetic pathway for anandamide in mouse brain…

Both PTPN22 and endocannabinoids have been implicated in autoimmune diseases, suggesting that the PLC/phosphatase pathway of anandamide synthesis may be a pharmacotherapeutic target.

The observed exclusive role of the PLC/phosphatase pathway in LPS-induced AEA synthesis may offer therapeutic targets for the treatment of these conditions.

Furthermore, cannabinoids have immunosuppressive effects in autoimmune models of multiple sclerosis and diabetes, and mice deficient in CB1 receptors show increased susceptibility to neuronal damage found in autoimmune encephalitis…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1557387/#!po=23.3333

A potential role for GPR55 in the regulation of energy homeostasis.

Posted on January 1, 2014 by David

“G protein-coupled receptor 55 (GPR55) is a putative cannabinoid receptor that is expressed in several tissues involved in regulating energy homeostasis, including the hypothalamus, gastrointestinal tract, pancreas, liver, white adipose and skeletal muscle.

GPR55 has been shown to have a role in cancer and gastrointestinal inflammation, as well as in obesity and type 2 diabetes mellitus (T2DM).

Despite this, the (patho)physiological role of GPR55 in cell dysfunction is still poorly understood, largely because of the limited identification of downstream signalling targets.

Nonetheless, research has suggested that GPR55 modulation would be a useful pharmacological target in metabolically active tissues to improve treatment of diseases such as obesity and T2DM.

Further research is essential to gain a better understanding of the role that this receptor might have in these and other pathophysiological conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/24370891