The role of the endocannabinoid system in atherosclerosis.

Posted on June 5, 2014 by David

“Our current understanding of the pathophysiology of atherosclerosis suggests a prominent role for immune responses from its initiation through its complications. Given the increasing prevalence of cardiovascular risk factors worldwide, there is an urgent need to better understand the underlying mechanisms to improve current treatment protocols.

A growing body of evidence suggests that endocannabinoid signalling plays a critical role in the pathogenesis of atherogenesis and its clinical manifestations. Blocking CB(1) receptors has been shown to mediate not only weight reduction, but also several cardiometabolic effects in rodents and humans, indicating a potential relevance for the process of atherosclerosis.

Activation of CB(2) receptors with Delta(9)-tetrahydrocannabinol (THC) has been shown to inhibit atherosclerotic plaque progression in mice, mainly by inhibiting macrophage recruitment.

In conclusion, the precise role of the endocannabinoid system during atherosclerosis is not yet understood.”

http://www.ncbi.nlm.nih.gov/pubmed/18426500

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

Cannabinoid receptors in atherosclerosis.

Posted on June 5, 2014 by David

“…cannabinoid receptors are potential targets for the treatment of atherosclerosis…

Cannabinoids, such as Delta9-tetrahydrocannabinol, the major psychoactive compound of marijuana… was shown to inhibit disease progression through pleiotropic effects on inflammatory cells.

The development of novel cannabinoid receptor ligands that selectively target CB2 receptors or pharmacological modulation of the endocannabinoid system might offer novel therapeutic strategies in the treatment of atherosclerosis.

The immunomodulatory capacity of cannabinoids is now well established and suggests a broad therapeutic potential of cannabinoids for a variety of conditions, including atherosclerosis.”

http://www.ncbi.nlm.nih.gov/pubmed/16960500

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

Cannabinoid receptors in acute and chronic complications of atherosclerosis

Posted on June 5, 2014 by David

“Atherosclerosis is a chronic inflammatory disease that is the primary cause of myocardial infarction and stroke, which occur after sudden thrombotic occlusion of an artery.

A growing body of evidence suggests that cannabinoid signalling plays a fundamental role in atherosclerosis development and its clinical manifestations. Thus, CB2 receptors are protective in myocardial ischaemia/reperfusion and implicated in the modulation of chemotaxis, which is crucial for the recruitment of leukocytes during inflammation.

Delta-9-Tetrahydrocannabinol (THC)-mediated activation has been shown to inhibit atherosclerotic plaque progression in a CB2 dependent manner.

It is tempting to suggest that pharmacological modulation of the endocannabinoid system is a potential novel therapeutic strategy in the treatment of atherosclerosis.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219535/

Activation of cannabinoid CB2 receptor ameliorates atherosclerosis associated with suppression of adhesion molecules.

Posted on June 5, 2014 by David

“Adhesion molecules have been implicated in the development and progression of atherosclerosis. Cannabinoids have been reported to modulate the migration and adhesion molecules expression of various cell types.

Here we examined the effects of WIN55212-2, a cannabinoid receptor 1 (CB1-R)/cannabinoid receptor 2 (CB2-R) agonist on the development of atherosclerotic lesions…

WIN55212-2 seems to have direct anti-atherosclerotic effects in an animal model of atherosclerosis… these beneficial effects of WIN55212-2 may be mediated through the CB2 receptor.”

http://www.ncbi.nlm.nih.gov/pubmed/20075743

Towards a therapeutic use of selective CB2 cannabinoid receptor ligands for atherosclerosis.

Posted on June 5, 2014 by David

“Atherosclerosis remains the primary cause of heart disease and stroke, causing approximately 50% of all deaths in Western countries. The identification of promising novel anti-atherosclerotic therapies is therefore of great interest and represents a continued challenge to the medical community.

Cannabinoids, such as Delta9-tetrahydrocannabinol (THC), which is the major psychoactive compound of marijuana, modulate immune functions and might therefore be of therapeutic use for the treatment of inflammatory diseases.

The authors have demonstrated recently that oral treatment with low dose THC inhibits atherosclerosis progression in mice through pleiotropic immunomodulatory effects on inflammatory cells. All these effects were mediated via the cannabinoid receptor CB(2), the main cannabinoid receptor expressed on immune cells.

The identification and characterization of cannabinoid derivative that selectively activate CB(2) receptors and are devoid of adverse effects might offer a novel therapeutic strategy for the treatment of atherosclerosis.”

http://www.ncbi.nlm.nih.gov/pubmed/19804131

https://www.futuremedicine.com/doi/abs/10.2217/14796678.2.1.49

“Researchers suggest that THC and other cannabinoids, which are active at CB2, the cannabinoid receptor expressed on immune cells, may be valuable in treating atherosclerosis.” https://www.medscape.com/viewarticle/787468

Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice

Posted on June 5, 2014 by David

Figure 1 : The cannabinoid receptor CB2 is expressed in human and mouse atherosclerotic plaques. Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, or to obtain a text description, please contact npg@nature.com

“Atherosclerosis is a chronic inflammatory disease… Derivatives of cannabinoids such as delta-9-tetrahydrocannabinol (THC) modulate immune functions and therefore have potential for the treatment of inflammatory diseases.

We investigated the effects of THC in a murine model of established atherosclerosis.

Oral administration of THC resulted in significant inhibition of disease progression.

Our data demonstrate that oral treatment with a low dose of THC inhibits atherosclerosis progression in the apolipoprotein E knockout mouse model, through pleiotropic immunomodulatory effects on lymphoid and myeloid cells.

Thus, THC or cannabinoids with activity at the CB2 receptor may be valuable targets for treating atherosclerosis.”

http://www.nature.com/nature/journal/v434/n7034/full/nature03389.html

http://www.ncbi.nlm.nih.gov/pubmed/15815632

Marijuana Chemical Fights Hardened Arteries – WebMD

Posted on June 5, 2014 by David

“The active ingredient in marijuana that produces changes in brain messages appears to fight atherosclerosis — a hardening of the arteries.

It takes a very specific amount of THC — marijuana’s key chemical — to help the arteries. That dose is too low to produce mood-altering effects in the brain, according to the new study.

“It would be difficult to achieve such specific concentrations in the blood by smoking marijuana,” Roth explains in a Nature editorial.”

http://www.webmd.com/heart-disease/news/20050406/marijuana-chemical-fights-hardened-arteries

“Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice” http://www.nature.com/nature/journal/v434/n7034/full/nature03389.html

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

A new face of endocannabinoids in pharmacotherapy. Part I & II

Posted on May 5, 2014 by David

“A new face of endocannabinoids in pharmacotherapy. Part I: Protective role of endocannabinoids in hypertension and myocardial infarction.

Cannabinoids are compounds which were first isolated from the Cannabis sativa plant. For thousands of years they have been used for treatment of numerous diseases.

Currently, synthetic cannabinoids and endocannabinoids are also known. Cannabinoid receptors, endocannabinoids and the enzymes that catalyze their synthesis and degradation constitute the endocannabinoid system which plays an important role in functioning of the cardiovascular system.

The results obtained to date suggest the involvement of endocannabinoids in the pathology of many cardiovascular diseases, including myocardial infarction, hypertension and hypotension associated with hemorrhagic, endotoxic, and cardiogenic shock. Cardioprotective effect and dilation of coronary vessels induced by endocannabinoids deserve special attention.

It cannot be excluded now that in the future our better understanding of cannabinoid system will allow to develop new strategies for treatment of cardiovascular diseases.”

http://www.jpp.krakow.pl/journal/archive/04_14/pdf/171_04_14_article.pdf

“A new face of endocannabinoids in pharmacotherapy. Part II. Role of endocannabinoids in inflammation-derived cardiovaascular diseases.

Endocannabinoids play an important role in cardiovascular diseases caused by inflammatory disorders. Endocannabinoids are endogenous bioactive lipids that activate cannabinoid receptors and together with enzymes responsible for their synthesis and degradation constitute endocannabinoid system.

The results obtained to date suggest the involvement of endocannabinoids in the pathology of many cardiovascular diseases associated with inflammation, such as atherosclerosis, restenosis, chemotherapy-induced myocardial injury, diabetic and hepatic cirrhosis cardiomyopathy.

Our better understanding of cannabinoid system may result in the development of new strategies for the treatment of such disorders.”

http://www.jpp.krakow.pl/journal/archive/04_14/pdf/183_04_14_article.pdf

Δ9-tetrahydrocannabinol and its major metabolite Δ9-tetrahydrocannabinol-11-oic acid as 15-lipoxygenase inhibitors.

Posted on March 3, 2014 by David

“Δ(9)-Tetrahydrocannabinol (Δ(9)-THC), a major component of marijuana, has suggested to suppress atherosclerosis…. Δ(9)-THC seems to be attractive for the prevention of atherosclerosis…

In the present study, Δ(9)-THC was found to be a direct inhibitor for 15-LOX…

Furthermore, Δ(9)-THC-11-oic acid, a major and nonpsychoactive metabolite of Δ(9) -THC, but not another Δ(9)-THC metabolite 11-OH-Δ(9)-THC (psychoactive), was revealed to inhibit 15-LOX.

Taken together, it is suggested that Δ(9) -THC can abrogate atherosclerosis via direct inhibition of 15-LOX, and that Δ(9)-THC-11-oic acid is shown to be an “active metabolite” of Δ(9) -THC in this case.”

http://www.ncbi.nlm.nih.gov/pubmed/20891010

“15-lipoxygenase inhibitors as anti-atherosclerosis agents.” http://www.ncbi.nlm.nih.gov/pubmed/18465533

Cannabidiol-2′,6′-dimethyl ether, a cannabidiol derivative, is a highly potent and selective 15-lipoxygenase inhibitor.

Posted on March 3, 2014 by David

“Cannabidiol (CBD), one of the major components of marijuana, is known to inhibit LOX activity…

15-LOX is suggested to be involved in development of atherosclerosis, and CBDD may be a useful prototype for producing medicines for atherosclerosis.”

http://dmd.aspetjournals.org/content/37/8/1733.long

“15-lipoxygenase inhibitors as anti-atherosclerosis agents.” http://www.ncbi.nlm.nih.gov/pubmed/18465533