Tag Archives: Cannabinoids

Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells.

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“To investigate the regulation of cannabinoid receptors CB1 and CB2 on immune cells by proinflammatory cytokines and its potential relevance to the inflammatory neurological disease, multiple sclerosis (MS).

CB1 and CB2 signalling may be anti-inflammatory and neuroprotective in neuroinflammatory diseases.

Cannabinoids can suppress inflammatory cytokines…

The levels of CB1 and CB2 can be up-regulated by inflammatory cytokines, which can explain their increase in inflammatory conditions including MS”

http://www.ncbi.nlm.nih.gov/pubmed/25704169

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

The CB1 cannabinoid receptor signals striatal neuroprotection via a PI3K/Akt/mTORC1/BDNF pathway.

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“The CB1 cannabinoid receptor, the main molecular target of endocannabinoids and cannabis active components, is the most abundant G protein-coupled receptor in the mammalian brain.

In particular, the CB1 receptor is highly expressed in the basal ganglia, mostly on terminals of medium-sized spiny neurons, where it plays a key neuromodulatory function.

The CB1 receptor also confers neuroprotection in various experimental models of striatal damage…

Here, by using an array of pharmacological, genetic and pharmacogenetic approaches, we show that (1) CB1receptor engagement protects striatal cells from excitotoxic death via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin complex 1 pathway, which, in turn, (2) induces brain-derived neurotrophic factor (BDNF) expression through the selective activation of BDNF gene promoter IV, an effect that is mediated by multiple transcription factors.

Collectively, these findings unravel a molecular link between CB1 receptor activation and BDNF expression, and support the relevance of the CB1/BDNF axis in promoting striatal neuron survival.”

http://www.ncbi.nlm.nih.gov/pubmed/25698444

Cannabidiol (CBD) and its analogs: a review of their effects on inflammation.

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“First isolated from Cannabis in 1940 by Roger Adams, the structure of CBD was not completely elucidated until 1963.

Subsequent studies resulted in the pronouncement that THC was the ‘active’ principle of Cannabis and research then focused primarily on it to the virtual exclusion of CBD.

This was no doubt due to the belief that activity meant psychoactivity that was shown by THC and not by CBD.

In retrospect this must be seen as unfortunate since a number of actions of CBD with potential therapeutic benefit were downplayed for many years.

In this review, attention will be focused on the effects of CBD in the broad area of inflammation where such benefits seem likely to be developed.

Topics covered in this review are; the medicinal chemistry of CBD, CBD receptor binding involved in controlling Inflammation, signaling events generated by CBD, downstream events affected by CBD (gene expression and transcription), functional effects reported for CBD and combined THC plus CBD treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/25703248

Cannabinoid signaling and liver therapeutics.

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Journal of Hepatology Home

“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/

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/

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/

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

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“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/

Activation of Cannabinoid Receptor 2 Enhances Osteogenic Differentiation of Bone Marrow Derived Mesenchymal Stem Cells.

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“Bone marrow derived mesenchymal stem cells (BM-MSCs) are considered as the most promising cells source for bone engineering.

Cannabinoid(CB) receptors play important roles in bone mass turnover.

The aim of this study is to test if activation of CB2 receptor by chemical agonist could enhance the osteogenic differentiation and mineralization in bone BM-MSCs…

Taken together, data from this study suggested that activation of CB2 receptor plays important role in osteogenic differentiation of BM-MSCs.

Lack of CB2 receptor may be related to osteoporosis.

These results demonstrate that the activation of CB2 signaling is essential for the maintenance of normal bone mass.

Manipulating CB2 signaling may offer a molecular tool for the increasing osteogenic differentiation of stem cells.”

http://www.hindawi.com/journals/bmri/2015/874982/

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