Category Archives: Cardiovascular Disease

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

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“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.

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“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.

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“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

Protective Effects of Cannabidiol Against Hippocampal Cell Death and Cognitive Impairment Induced by Bilateral Common Carotid Artery Occlusion in Mice.

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“The present study investigated whether cannabidiol (CBD), a major non-psychoactive constituent of marijuana, protects against hippocampal neurodegeneration and cognitive deficits induced by brain ischemia in adult mice…

These findings suggest a protective effect of CBD on neuronal death induced by ischemia and indicate that CBD might exert beneficial therapeutic effects in brain ischemia. The mechanisms that underlie the neuroprotective effects of CBD in BCCAO mice might involve the inhibition of reactive astrogliosis.”

http://www.ncbi.nlm.nih.gov/pubmed/24532152

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

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“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

Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart.

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“Cannabinoid receptor type 2 (CB2) activation is recently reported to promote proliferation of some types of resident stem cells (e.g., hematopoietic stem/progenitor cell or neural progenitor cell).

Resident cardiac progenitor cell (CPC) activation and proliferation are crucial for endogenous cardiac regeneration and cardiac repair after myocardial infarction (MI). This study aims to explore the role and possible mechanisms of CB2 receptor activation in enhancing myocardial repair…

In conclusion, AM1241 could induce myocardial regeneration and improve cardiac function, which might be associated with PI3K/Akt/Nrf2 signaling pathway activation.

Our findings may provide a promising strategy for cardiac endogenous regeneration after MI.”

http://www.ncbi.nlm.nih.gov/pubmed/24430557

Improved Cardiac and Neurologic Outcomes With Postresuscitation Infusion of Cannabinoid Receptor Agonist WIN55, 212-2 Depend on Hypothermia in a Rat Model of Cardiac Arrest*.

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“OBJECTIVES: To investigate the mechanisms of improved myocardial and neurological function and survival following IV administration of cannabinoid receptor agonist, WIN55, 212-2 in a rat model of cardiac arrest…

CONCLUSIONS: In a rat model of cardiac arrest, better postresuscitation myocardial function, neurological deficit scores, and longer duration of survival were observed by the pharmacologically induced hypothermia with WIN55, 212-2. The improved outcomes of cardiopulmonary resuscitation following administration of WIN55, 212-2 appeared to be the results from its temperature reduction effects.”

http://www.ncbi.nlm.nih.gov/pubmed/24346544

Therapeutic potential of cannabinoid medicines.

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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

New Study: Cannabinoids Protect the Brain and Heart From Injury

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“Cannabis is in the news again for its purported medicinal benefits, with researchers in Israel last week indicating it may help prevent trauma to the brain in certain circumstances and may also help with cardiac problems. A few months ago an English pharmaceutical company that manufactures cannabinoids announced it was developing a new treatment for epilepsy using them.”

Los Angeles City Council Votes To Ban Medical Marijuana Dispensaries

“Prof. Yosef Sarne in the Adelson Center for the Biology of Addictive Diseases in the Department of Physiology and Pharmacology at Tel Aviv University says that cannabis has neuro-protective qualities. He has found that extremely low doses of tetrahydrocannabinol or THC- the psychoactive component of marijuana- can protect the brain from long-term cognitive damage in the wake of injury from hypoxia (lack of oxygen), seizures, or toxic drugs.”

More: http://jewishbusinessnews.com/2013/06/09/new-study-cannabinoids-protect-the-brain-and-heart-from-injury/

The endocannabinoid system and its therapeutic exploitation.

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“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