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/

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

Detailed characterization of the endocannabinoid system in human macrophages and foam cells, and anti-inflammatory role of type-2 cannabinoid receptor.

Posted on February 18, 2014 by David

“Here, we sought to ascertain whether different elements of the endocannabinoid system (ECS) were activated in human lipid-laden macrophages, and whether CB2R played any role in atherogenesis and inflammation of these cells…

CONCLUSIONS:

A fully active ECS is present in human macrophages and macrophage-derived foam cells. Selective activation of CB2R reduces CD36-dependent oxLDL accumulation and modulates production of inflammatory cytokines, thus representing a potential therapeutic strategy to combat atherosclerosis.”

http://www.ncbi.nlm.nih.gov/pubmed/24529123

Therapeutic potential of cannabinoid medicines.

Posted on September 6, 2013 by David

Drug Testing and Analysis

“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.

The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.

In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24006213

http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract

The endocannabinoid system and its therapeutic exploitation.

Posted on May 24, 2013 by David

Image result for Nat Rev Drug Discov.

“The term ‘endocannabinoid’ – originally coined in the mid-1990s after the discovery of membrane receptors for the psychoactive principle in Cannabis, Delta9-tetrahydrocannabinol and their endogenous ligands – now indicates a whole signalling system that comprises cannabinoid receptors, endogenous ligands and enzymes for ligand biosynthesis and inactivation. This system seems to be involved in an ever-increasing number of pathological conditions. With novel products already being aimed at the pharmaceutical market little more than a decade since the discovery of cannabinoid receptors, the endocannabinoid system seems to hold even more promise for the future development of therapeutic drugs. We explore the conditions under which the potential of targeting the endocannabinoid system might be realized in the years to come.” http://www.ncbi.nlm.nih.gov/pubmed/15340387

http://www.nature.com/nrd/journal/v3/n9/full/nrd1495.html

Cannabidiol as an Emergent Therapeutic Strategy for Lessening the Impact of Inflammation on Oxidative Stress

Posted on January 10, 2013 by David

“Growing evidence suggests that the endocannabinoid system, which includes the CB₁ and CB₂ G protein-coupled receptors and their endogenous lipid ligands, may be an area that is ripe for therapeutic exploitation. In this context, the related nonpsychotropic cannabinoid cannabidiol, which may interact with the endocannabinoid system, but has actions that are distinct, offers promise as a prototype for anti-inflammatory drug development.

This review discusses recent studies suggesting that cannabidiol may have utility in treating a number of human diseases and disorders now known to involve activation of the immune system and associated oxidative stress, as a contributor to their etiology and progression. These include rheumatoid arthritis, types I and II diabetes, atherosclerosis, Alzheimer’s disease, hypertension, the metabolic syndrome, ischemia-reperfusion injury, depression, and neuropathic pain.

Cannabidiol (CBD) is the major nonpsychotropic cannabinoid compound derived from the plant Cannabis sativa, commonly known as marijuana…

Conclusions

Inflammation and oxidative stress are intimately involved in the genesis of many human diseases. Unraveling that relationship therapeutically has proven challenging, in part because inflammation and oxidative stress “feed off” each other. However, CBD would seem to be a promising starting point for further drug development given its anti-oxidant (although relatively modest) and anti-inflammatory actions on immune cells, such as macrophages and microglia. CBD also has the advantage of not having psychotropic side effects. Studies on models of human diseases support the idea that CBD attenuates inflammation far beyond its antioxidant properties, for example, by targeting inflammation-related intracellular signaling events. The details on how CBD targets inflammatory signaling remain to be defined.

The therapeutic utility of CBD is a relatively new area of investigation that portends new discoveries on the interplay between inflammation and oxidative stress, a relationship that underlies tissue and organ damage in many human diseases.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085542/