Effects of intra-infralimbic prefrontal cortex injections of cannabidiol in the modulation of emotional behaviors in rats: contribution of 5HT1A receptors and stressful experiences.

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“The infralimbic (IL) and prelimbic (PL) regions of the prefrontal cortex are involved in behavioral responses observed during defensive reactions.

Intra-PL or IL injections of cannabidiol (CBD), a major non-psychotomimetic cannabinoid present in the Cannabis sativa plant, result in opposite behavioral effects in the contextual fear conditioning (CFC) paradigm…

Together these results indicate that CBD effects in the IL depend on the nature of the animal model, being influenced by previous stressful experiences and mediated by facilitation of 5HT1A receptors-mediated neurotransmission.”

http://www.ncbi.nlm.nih.gov/pubmed/25701682

Cannabinoid signaling and liver therapeutics.

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“Over the last decade, the endocannabinoid system has emerged as a pivotal mediator of acute and chronic liver injury, with the description of the role of CB1 and CB2 receptors and their endogenous lipidic ligands in various aspects of liver pathophysiology.

A large number of studies have demonstrated that CB1 receptor antagonists represent an important therapeutic target, owing to beneficial effects on lipid metabolism and in light of its antifibrogenic properties.

Unfortunately, the brain-penetrant CB1 antagonist rimonabant, initially approved for the management of overweight and related cardiometabolic risks, was withdrawn because of an alarming rate of mood adverse effects.

However, the efficacy of peripherally-restricted CB1 antagonists with limited brain penetrance has now been validated in preclinical models of NAFLD, and beneficial effects on fibrosis and its complications are anticipated.

CB2 receptor is currently considered as a promising anti-inflammatory and antifibrogenic target, although clinical development of CB2 agonists is still awaited.

In this review, we highlight the latest advances on the impact of the endocannabinoid system on the key steps of chronic liver disease progression and discuss the therapeutic potential of molecules targeting cannabinoid receptors…

Overwhelming evidence supports the therapeutic potential of peripherally-restricted CB1 antagonists and CB2 agonists in the management of chronic liver diseases.”

http://www.journal-of-hepatology.eu/article/S0168-8278(13)00212-2/fulltext

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

Cannabinoid CB2 receptors protect against alcoholic liver disease by regulating Kupffer cell polarization in mice.

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“Activation of Kupffer cells plays a central role in the pathogenesis of alcoholic liver disease.

Because cannabinoid CB2 receptors (CB2) display potent anti-inflammatory properties, we investigated their role in the pathogenesis of alcoholic liver disease, focusing on the impact of CB2 on Kupffer cell polarization and the consequences on liver steatosis.

Altogether, these findings demonstrate that CB2 receptors display beneficial effects on alcohol-induced inflammation by regulating M1/M2 balance in Kupffer cells, thereby reducing hepatocyte steatosis via paracrine interactions between Kupffer cells and hepatocytes.

These data identify CB2 agonists as potential therapeutic agents for the management of alcoholic liver disease.”

http://www.ncbi.nlm.nih.gov/pubmed/21735467

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

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

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“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/

Cannabinoids and capsaicin improve liver function following thioacetamide-induced acute injury in mice.

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“We have shown the beneficial effects of cannabinoids in a murine model of hepatic encephalopathy following thioacetamide and now report their effects on the liver injury…

The similar pattern found between the effect of cannabinoids and their antagonists on brain and liver indicated that the therapeutic effect might be directed by the improvement in both organs through CB2 receptors and/or TRPV1 receptors.

Modulation of these systems may have therapeutic potential.”

http://www.ncbi.nlm.nih.gov/pubmed/19086956

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

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

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“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.

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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/

Regulation of nausea and vomiting by cannabinoids and the endocannabinoid system.

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“One of the oldest pharmacological remedies for nausea and vomiting is the plant cannabis…

Cannabis has long been known to limit or prevent nausea and vomiting from a variety of causes.

This has led to extensive investigations that have revealed an important role for cannabinoids and their receptors in the regulation of nausea and emesis.

With the discovery of the endocannabinoid system, novel ways to regulate both nausea and vomiting have been discovered that involve the production of endogenous cannabinoids acting centrally.

Here we review recent progress in understanding the regulation of nausea and vomiting by cannabinoids and the endocannabinoid system, and we discuss the potential to utilize the endocannabinoid system in the treatment of these frequently debilitating conditions…

Nausea and vomiting are frequently debilitating conditions that require substantial effort and cost to manage.

Advances in recent progress in understanding the regulation of nausea and vomiting by cannabinoids and the endocannabinoid system have revealed significant potential for therapeutic approaches to be developed.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883513/

http://www.thctotalhealthcare.com/category/nauseavomiting/

Components of the endocannabinoid and dopamine systems are dysregulated in Huntington’s disease: analysis of publicly available microarray datasets.

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“The endocannabinoid system (ECS) and the dopaminergic system (DAS) are two major regulators of basal ganglia function. During Huntington’s disease (HD) pathogenesis, the expression of genes in both the ECS and DAS is dysregulated…

The resulting data confirm gene expression changes observed using different approaches and provide novel insights into the consistency between changes observed in human tissue and various models, as well as disease stage- and tissue-specific transcriptional dysregulation in HD.

The major implication of the systems-wide data presented here is that therapeutic strategies targeting the ECS or DAS must consider the dynamic changes in gene expression over time and in different body areas, which occur during HD progression and the interconnectedness of the two systems.”

http://www.ncbi.nlm.nih.gov/pubmed/25692022

http://www.thctotalhealthcare.com/category/huntingtons/

Cannabinoids suppress acute and anticipatory nausea in pre-clinical rat models of conditioned gaping.

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“The sensation of nausea is one of the most debilitating human experiences. Current anti-emetic therapies are effective in reducing vomiting, but are less effective in reducing acute and delayed nausea and are completely ineffective in reducing anticipatory nausea.

Recent pre-clinical evidence using a selective rat model of nausea (conditioned gaping reactions) has revealed that cannabinoids have great promise as treatments for nausea and that their anti-nausea effects may be mediated by the interoceptive insular cortex.”

http://www.ncbi.nlm.nih.gov/pubmed/25691302

http://www.thctotalhealthcare.com/category/nauseavomiting/