Tag Archives: endocannabinoid system

Control of Breast Cancer by the Endocannabinoid System

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“Activation of the endocannabinoid system through CB1, CB2 and additional receptor subtypes results in the inhibition of a broad range of cancers.

The endocannabinoid system was discovered through research focusing on the classical cannabinoid agonist, ?9-tetrahydrocannabinol (?9-THC), and other synthetic cannabinoids.

This proposal will focus on the potential treatment of human breast cancer using cannabinoids as selective antitumor agents.

We have found that cannabinoid compounds activating CB1, CB2 and additional receptor subtypes can inhibit breast cancer cell proliferation and invasiveness and we have discovered down-stream targets that potentially link cannabinoid receptor stimulation to these effects.

Furthermore, our preliminary studies provide evidence that endogenous endocannabinoid tone tonically inhibits metastatic breast cancer cell proliferation and invasiveness through the activation of cannabinoid receptors.

Our preliminary data also suggests that cannabinoid compounds possess selective efficacy, having less adverse effects on the normal human cells from which the breast cancers arise.

Since toxicity in healthy tissue limits the efficacy of current cancer treatments, discovering the mechanism behind selective efficacy in human tissues is of clinical importance.

Cannabinoids can inhibit multiple types of tumor growth in vivo…

Testing the hypotheses outlined in the application may lead to the development of effective inhibitors of breast, and perhaps other, cancers.

This research may also elucidate novel mechanisms related to the anticancer activity of cannabinoids, and will serve to develop the career of the candidate in the field of cancer biology.”

 http://grantome.com/grant/NIH/K01-CA111723-01A2

http://www.thctotalhealthcare.com/category/breast-cancer/

Targeting the endocannabinoid system to treat anxiety-related disorders.

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“The endocannabinoid system plays an important role in the control of emotions, and its dysregulation has been implicated in several psychiatric disorders.

The most common self-reported reason for using cannabis is rooted in its ability to reduce feelings of stress, tension, and anxiety.

Nevertheless, there are only few studies in controlled clinical settings that confirm that administration of cannabinoids can benefit patients with a post-traumatic stress disorder (PTSD).

There are considerable encouraging preclinical data to suggest that endocannabinoid-targeted therapeutics for anxiety disorders should continue.

In this review, we will describe data supporting a role for the endocannabinoid system in preventing and treating anxiety-like behavior in animal models and PTSD patients.

Cannabinoids have shown beneficial outcomes in rat and mouse models of anxiety and PTSD, but they also may have untoward effects that discourage their chronic usage, including anxiogenic effects.

Hence, clinical and preclinical research on the endocannabinoid system should further study the effects of cannabinoids on anxiety and help determine whether the benefits of using exogenous cannabinoids outweigh the risks.

In general, this review suggests that targeting the endocannabinoid system represents an attractive and novel approach to the treatment of anxiety-related disorders and, in particular, PTSD.”

http://www.ncbi.nlm.nih.gov/pubmed/26426887

Cannabis – the Israeli perspective.

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“Short overviews are presented on the historical uses of cannabis in the Middle East and on the more recent scientific and medical research on phytocannabinoids and the endocannabinoid system, with emphasis on research contributions from Israel. These are followed by examples of research projects and clinical trials with cannabinoids and by a short report on the regulation of medical marijuana in Israel, which at present is administered to over 22,000 patients.”

http://www.ncbi.nlm.nih.gov/pubmed/26426888

Protection from Radiation-Induced Pulmonary Fibrosis by Peripheral Targeting of Cannabinoid Receptor-1.

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“Radiation-induced pulmonary fibrosis (RIF) is a severe complication of thoracic radiotherapy that limits its dose, intensity, and duration. The contribution of the endocannabinoid signaling system in pulmonary fibrogenesis is not known. Using a well-established mouse model of RIF, we assessed the involvement of cannabinoid receptor-1 (CB1) in the onset and progression of pulmonary fibrosis.

Our results show that CB1 signaling plays a key pathological role in the development of radiation-induced pulmonary inflammation and fibrosis, and peripherally restricted CB1 antagonists may represent a novel therapeutic approach against this devastating complication of radiotherapy/irradiation.”

http://www.ncbi.nlm.nih.gov/pubmed/26426981

“We report for the first time the involvement of cannabinoid receptor 1 (CB1)-mediated signaling in the onset and progression of radiation-induced pulmonary fibrosis (RIF). We were able to delay the onset of RIF by genetic targeting of CB1 receptors as well as by its pharmacological inhibition. Thus, pharmacological targeting of CB1 receptors with peripherally restricted CB1 antagonists void of central nervous system complications may represent a novel strategy to prevent the development of RIF.

In summary, we provide the first evidence on the key pathological role of CB1 signaling in radiation-induced pulmonary fibrogenesis and show that peripherally restricted CB1 antagonists may represent a novel therapeutic approach against this devastating and untreatable complication of radiotherapy/irradiation. Our results also suggest that targeting CB1 may provide benefits in other lung diseases associated with inflammation and fibrosis.”

http://www.atsjournals.org/doi/10.1165/rcmb.2014-0331OC

Potential Therapeutical Contributions of the Endocannabinoid System towards Aging and Alzheimer’s Disease.

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“Aging can lead to decline in cognition, notably due to neurodegenerative processes overwhelming the brain over time.

As people live longer, numerous concerns are rightfully raised toward long-term slowly incapacitating diseases with no cure, such as Alzheimer’s disease.

Since the early 2000’s, the role of neuroinflammation has been scrutinized for its potential role in the development of diverse neurodegenerative diseases notably because of its slow onset and chronic nature in aging.

Despite the lack of success yet, treatment of chronic neuroinflammation could help alleviate process implicated in neurodegenerative disease.

A growing number of studies including our own have aimed at the endocannabinoid system and unfolded unique effects of this system on neuroinflammation, neurogenesis and hallmarks of Alzheimer’s disease and made it a reasonable target in the context of normal and pathological brain aging.”

http://www.ncbi.nlm.nih.gov/pubmed/26425394

The Endocannabinoid System: Pivotal Orchestrator of Obesity and Metabolic Disease.

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“The endocannabinoid system (ECS) functions to adjust behavior and metabolism according to environmental changes in food availability.

Its actions range from the regulation of sensory responses to the development of preference for the consumption of calorically-rich food and control of its metabolic handling.

ECS activity is beneficial when access to food is scarce or unpredictable.

However, when food is plentiful, the ECS favors obesity and metabolic disease.

We review recent advances in understanding the roles of the ECS in energy balance, and discuss newly identified mechanisms of action that, after the withdrawal of first generation cannabinoid type 1 (CB1) receptor antagonists for the treatment of obesity, have made the ECS once again an attractive target for therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/26412154

https://www.cell.com/trends/endocrinology-metabolism/fulltext/S1043-2760(15)00140-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS104327601500140X%3Fshowall%3Dtrue

Endocannabinoids and Cancer.

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“A large body of evidence shows that cannabinoids, in addition to their well-known palliative effects on some cancer-associated symptoms, can reduce tumour growth in animal models of cancer.

They do so by modulating key cell signalling pathways involved in the control of cancer cell proliferation and survival.

In addition, cannabinoids inhibit angiogenesis and cell proliferation in different types of tumours in laboratory animals.

By contrast, little is known about the biological role of the endocannabinoid system in cancer physio-pathology, and several studies suggest that it may be over-activated in cancer.

In this review, we discuss our current understanding of cannabinoids as antitumour agents, focusing on recent advances in the molecular mechanisms of action, including resistance mechanisms and opportunities for combination therapy approaches.”

http://www.ncbi.nlm.nih.gov/pubmed/26408171

Endocannabinoids and the Digestive Tract and Bladder in Health and Disease.

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“Components of the so-called endocannabinoid system, i.e., cannabinoid receptors, endocannabinoids, as well as enzymes involved in endocannabinoid synthesis and degradation, have been identified both in the gastrointestinal and in the urinary tract.

Evidence suggests that the endocannabinoid system is implicated in many gastrointestinal and urinary physiological and pathophysiological processes, including epithelial cell growth, inflammation, analgesia, and motor function.

A pharmacological modulation of the endocannabinoid system might be beneficial for widespread diseases such as gastrointestinal reflux disease, irritable bowel syndrome, inflammatory bowel disease, colon cancer, cystitis, and hyperactive bladder.

Drugs that inhibit endocannabinoid degradation and raise the level of endocannabinoids, non-psychotropic cannabinoids (notably cannabidiol), and palmitoylethanolamide, an acylethanolamide co-released with the endocannabinoid anandamide, are promising candidates for gastrointestinal and urinary diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/26408170

Endocannabinoids and the Cardiovascular System in Health and Disease.

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“The endocannabinoid system is widely distributed throughout the cardiovascular system.

Endocannabinoids play a minimal role in the regulation of cardiovascular function in normal conditions, but are altered in most cardiovascular disorders.

In shock, endocannabinoids released within blood mediate the associated hypotension through CB1 activation. In hypertension, there is evidence for changes in the expression of CB1, and CB1 antagonism reduces blood pressure in obese hypertensive and diabetic patients.

The endocannabinoid system is also upregulated in cardiac pathologies.

This is likely to be cardioprotective, via CB2 and CB1 (lesser extent).

In the vasculature, endocannabinoids cause vasorelaxation through activation of multiple target sites, inhibition of calcium channels, activation of potassium channels, NO production and the release of vasoactive substances. Changes in the expression or function of any of these pathways alter the vascular effect of endocannabinoids.

Endocannabinoids have positive (CB2) and negative effects (CB1) on the progression of atherosclerosis. However, any negative effects of CB1 may not be consequential, as chronic CB1 antagonism in large scale human trials was not associated with significant reductions in atheroma.

In neurovascular disorders such as stroke, endocannabinoids are upregulated and protective, involving activation of CB1, CB2, TRPV1 and PPARα.

Although most of this evidence is from preclinical studies, it seems likely that cannabinoid-based therapies could be beneficial in a range of cardiovascular disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26408169

Endocannabinoids and Metabolic Disorders.

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“The endocannabinoid system (ECS) is known to exert regulatory control on essentially every aspect related to the search for, and the intake, metabolism and storage of calories, and consequently it represents a potential pharmacotherapeutic target for obesity, diabetes and eating disorders.

While the clinical use of the first generation of cannabinoid type 1 (CB1) receptor blockers has been halted due to the psychiatric side effects that their use occasioned, recent research in animals and humans has provided new knowledge on the mechanisms of actions of the ECS in the regulation of eating behavior, energy balance, and metabolism.

In this review, we discuss these recent advances and how they may allow targeting the ECS in a more specific and selective manner for the future development of therapies against obesity, metabolic syndrome, and eating disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26408168