Tag Archives: CB2

Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice

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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

 

Cannabinoids in pain management: CB1, CB2 and non-classic receptor ligands.

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“The available commercial cannabinoids have a narrow therapeutic index. Recently developed peripherally restricted cannabinoids, regionally administered cannabinoids, bifunctional cannabinoid ligands and cannabinoid enzyme inhibitors, endocannabinoids, which do not interact with classic cannabinoid receptors (CB1r and CB2r), cannabinoid receptor antagonists and selective CB1r agonists hold promise as analgesics…

Expert opinion: Regional and peripherally restricted cannabinoids will reduce cannabinomimetic side effects. Spinal cannabinoids may increase the therapeutic index by limiting the dose necessary for response and minimize drugs exposure to supraspinal sites where cannabinomimetic side effects originate. Cannabinoid bifunctional ligands should be further explored. The combination of a CB2r agonist with a transient receptor potential vanilloid (TRPV-1) antagonist may improve the therapeutic index of the CB2r agonist. Enzyme inhibitors plus TRPV-1 blockers should be further explored. The development of analgesic tolerance with enzyme inhibitors and the pronociceptive effects of prostamides limit the benefits to cannabinoid hydrolyzing enzyme inhibitors.

Most clinically productive development of cannabinoids over the next 5 years will be in the area of selective CB2r agonists. These agents will be tested in various inflammatory, osteoarthritis and neuropathic pains.”

http://www.ncbi.nlm.nih.gov/pubmed/24836296

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

Endocannabinoid signaling in Alzheimer’s disease: current knowledge and future directions.

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“The importance of the endocannabinoid system (ECS) in the modulation functions of the central nervous system has been extensively investigated during the last few years. In particular, accumulated evidence has implicated ECS in the pathophysiology of Alzheimer’s disease (AD), that is a progressive, degenerative, and irreversible disorder characterized by the accumulation in the brain of beta-amyloid fragments forming insoluble plaques, and of intracellular neurofibrillary tangles (NTFs) associated with synaptic and neuronal loss. In all the processes involved in the formation of both plaques and NFTs, the key-role played by the ECS has been documented. Here, we review current knowledge and future directions of ECS modulation both in animal models of AD and in human tissues, underlying the role of endocannabinoid signaling in the development of AD hallmarks. Overall, the available data suggest that next generation therapeutics might target distinct ECS elements, for instance CB2 receptor or fatty acid amide hydrolase, as a promising approach to halt or at least to slow down disease progression.”

http://www.ncbi.nlm.nih.gov/pubmed/24813316

http://www.thctotalhealthcare.com/category/alzheimers-disease-ad/

Functionalization of β-Caryophyllene Generates Novel Polypharmacology in the Endocannabinoid System.

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“The widespread dietary plant sesquiterpene hydrocarbon β-caryophyllene is a CB2 cannabinoid receptor-specific agonist showing anti-inflammatory and analgesic effects in vivo…

Our study shows that by removing the conformational constraints induced by the medium-sized ring and by introducing functional groups in the sesquiterpene hydrocarbon 1, a new scaffold with pronounced polypharmacological features within the endocannabinoid system could be generated.

The structural and functional repertoire of cannabimimetics and their yet poorly understood intrinsic promiscuity may be exploited to generate novel probes and ultimately more effective drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/24831513

“Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception…β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis… The combined injection of morphine and BCP may be an alternative in treating chemogenic pain.” http://www.ncbi.nlm.nih.gov/pubmed/23138934

CB2 cannabinoid receptors contribute to bacterial invasion and mortality in polymicrobial sepsis.

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“Sepsis is a major healthcare problem and current estimates suggest that the incidence of sepsis is approximately 750,000 annually. Sepsis is caused by an inability of the immune system to eliminate invading pathogens.

Here we examined the role of CB(2) receptors in regulating the host’s response to sepsis…

Taken together, our results establish for the first time that CB(2) receptors are important contributors to septic immune dysfunction and mortality, indicating that CB(2) receptors may be therapeutically targeted for the benefit of patients suffering from sepsis.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712683/

Cannabinoid receptor 2 activation reduces intestinal leukocyte recruitment and systemic inflammatory mediator release in acute experimental sepsis.

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“The aim of this study was to investigate the effects of CB2R manipulation on leukocyte activation within the intestinal microcirculation in two acute experimental sepsis models…

CB2R activation reduces leukocyte activation and systemic release of inflammatory mediators in acute experimental sepsis. Drugs targeting the CB2R pathway may have therapeutic potential in sepsis.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681373/

The cannabinoid 2 receptor as a potential therapeutic target for sepsis.

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“The sepsis syndrome represents an improper immune response to pathogens and is associated with an unacceptably high rate of mortality. Although supportive care is of benefit to the septic patient, there are no viable therapeutics available that target the immune system suitable for the whole septic population. Recently, using a physiologically relevant murine mouse model, the cannabiniod 2 receptor has been shown to play a critical role in the host response to sepsis. Here, the structure, expression, signaling, and function of the CB2 receptor on leukocytes will be reviewed. Further, the effects mediated by the CB2 receptor during sepsis will be reviewed. Altogether, alterations in inflammation and the host response during sepsis by the CB2 receptor support its use as a possible therapeutic agent.”

http://www.ncbi.nlm.nih.gov/pubmed/20509835

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

Experimental cannabinoid 2 receptor-mediated immune modulation in sepsis.

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“Sepsis is a complex condition that results from a dysregulated immune system in response to a systemic infection. Current treatments lack effectiveness in reducing the incidence and mortality associated with this disease. The endocannabinoid system offers great promise in managing sepsis pathogenesis due to its unique characteristics.

The present study explored the effect of modulating the CB2 receptor pathway in an acute sepsis mouse model.

Using various compounds we have shown different mechanisms of activating CB2 receptors to reduce leukocyte endothelial interactions in order to prevent further inflammatory damage during sepsis.”

http://www.ncbi.nlm.nih.gov/pubmed/24803745