Tag Archives: CB(1) and CB(2) receptors

Cannabinoid receptors in acute and chronic complications of atherosclerosis

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“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/

CBD-Rich Marijuana Fights Colon Cancer, New Study Finds

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“In 2008, over one million individuals were diagnosed with colon cancer, also known as colorectal cancer or bowel cancer and it caused over 600,000 deaths globally. The results of a study published in the journal Phytomedicine in October 2013 suggest that a botanical extract made from high-CBD (cannabidiol) cannabis can selectively target colon cancer cells, while leaving healthy cells unharmed.

Researchers were able to reduce tumor growth and pre-cancerous lesions in mice with colon cancer using the pot molecule CBD as part of a “botanical drug substance”. The authors believe that CBD’s benefits as demonstrated by the results of the study could have clinical relevance for the use of cannabis-based medicines in cancer patients.

Current colon cancer treatments are not only very toxic but also fail to prevent the progression of the disease in some patients. Disease incidence and mortality have not reduced using screening strategies for colon cancer.

Researchers have made progress in investigating cannabis as a treatment for breast and brain cancers considering its antiproliferative CB1 and CB2-mediated effects in colorectal cancer cells and action in experimental models of colon cancer. The study was partially funded through grants from GW Pharmaceuticals and lead by researchers from Italy and the UK.”

http://blog.sfgate.com/smellthetruth/2014/01/06/cbd-rich-marijuana-fights-colon-cancer-new-study-finds/

“Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol” http://www.ncbi.nlm.nih.gov/pubmed/24373545

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

Δ8-Tetrahydrocannabivarin prevents hepatic ischaemia/reperfusion injury by decreasing oxidative stress and inflammatory responses through cannabinoid CB2 receptors.

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“Activation of cannabinoid CB(2) receptors protects against various forms of ischaemia-reperfusion (I/R) injury.

Δ(8) -Tetrahydrocannabivarin (Δ(8) -THCV) is a synthetic analogue of the plant cannabinoid Δ(9) -tetrahydrocannabivarin, which exhibits anti-inflammatory effects in rodents involving activation of CB(2) receptors. Here, we assessed effects of Δ(8) -THCV and its metabolite 11-OH-Δ(8) -THCV on CB(2) receptors and against hepatic I/R injury.

CONCLUSIONS AND IMPLICATIONS:

Δ(8) -THCV activated CB(2) receptors in vitro, and decreased tissue injury and inflammation in vivo, associated with I/R partly via CB(2) receptor activation.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3423240/

The plant cannabinoid Delta9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice.

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“The phytocannabinoid, Delta(9)-tetrahydrocannabivarin (THCV), can block cannabinoid CB(1) receptors… THCV can activate CB(2) receptors… THCV can activate CB2 receptors and decrease signs of inflammation and inflammatory pain in mice partly via CB1 and/or CB2 receptor activation…

Because there is evidence that THCV can behave as a CB1 receptor antagonist in vivo, it would also be of interest to explore the possibility that this compound can suppress unwanted symptoms in animal models of disorders in which symptoms can be ameliorated by a combination of CB2 receptor activation and CB1 receptor blockade…”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931567/

Δ9-tetrahydrocannabinol prevents methamphetamine-induced neurotoxicity.

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“Methamphetamine (METH) is a potent psychostimulant with neurotoxic properties…

Preclinical studies have shown that natural (Δ9-tetrahydrocannabinol, Δ9-THC) and synthetic cannabinoid CB1 and CB2 receptor agonists exert neuroprotective effects on different models of cerebral damage. Here, we investigated the neuroprotective effect of Δ9-THC on METH-induced neurotoxicity…

Our results indicate that Δ9-THC reduces METH-induced brain damage via inhibition of nNOS expression and astrocyte activation through CB1-dependent and independent mechanisms, respectively.”

http://www.ncbi.nlm.nih.gov/pubmed/24844285

Full-text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4028295/

The influence of cannabinoids on generic traits of neurodegeneration

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“In an increasingly ageing population, the incidence of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease are rising. While the aetiologies of these disorders are different, a number of common mechanisms that underlie their neurodegenerative components have been elucidated; namely neuroinflammation, excitotoxicity, mitochondrial dysfunction and reduced trophic support. Current therapies focus on treatment of the symptoms and attempt to delay the progression of these diseases but there is currently no cure.

Modulation of the endogenous cannabinoid system is emerging as a potentially viable option in the treatment of neurodegeneration. Endocannabinoid signalling has been found to be altered in many neurodegenerative disorders. To this end, pharmacological manipulation of the endogenous cannabinoid system, as well as application of phytocannabinoids and synthetic cannabinoids have been investigated. Signalling from the CB1 and CB2 receptors are known to be involved in the regulation of Ca2+ homeostasis, mitochondrial function, trophic support and inflammatory status, respectively, while other receptors gated by cannabinoids such as PPARγ, are gaining interest in their anti-inflammatory properties.

Through multiple lines of evidence, this evolutionarily conserved neurosignalling system has shown neuroprotective capabilities and is therefore a potential target for neurodegenerative disorders. This review details the mechanisms of neurodegeneration and highlights the beneficial effects of cannabinoid treatment.”

http://onlinelibrary.wiley.com/doi/10.1111/bph.12492/full

Mitochondria: A Possible Nexus for the Regulation of Energy Homeostasis by the Endocannabinoid System?

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“The endocannabinoid system (ECS) regulates numerous cellular and physiological processes through the activation of receptors targeted by endogenously produced ligands called endocannabinoids. Importantly, this signalling system is known to play an important role in modulating energy balance and glucose homeostasis. For example, current evidence indicates that the ECS becomes overactive during obesity whereby its central and peripheral stimulation drives metabolic processes that mimic the metabolic syndrome. Herein, we examine the role of the ECS in modulating the function of mitochondria which play a pivotal role in maintaining cellular and systemic energy homeostasis, in large part due to their ability to tightly coordinate glucose and lipid utilisation. Because of this, mitochondrial dysfunction is often associated with peripheral insulin resistance and glucose intolerance, as well as the manifestation of excess lipid accumulation in the obese state. This review aims to highlight the different ways through which the ECS may impact upon mitochondrial abundance and/or oxidative capacity, and where possible, relate these findings to obesity-induced perturbations in metabolic function. Furthermore, we explore the potential implications of these findings in terms of the pathogenesis of metabolic disorders and how these may be used to strategically develop therapies targeting the ECS.”

http://www.ncbi.nlm.nih.gov/pubmed/24801388

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

Cannabinoid-induced autophagy regulates suppressor of cytokine signaling (SOCS)-3 in intestinal epithelium.

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“Autophagy is a catabolic process involved in homeostatic and regulated cellular protein recycling and degradation via the lysosomal degradation pathway. Emerging data associates impaired autophagy, increased activity in the endocannabinoid system and upregulation of suppressor of cytokine signaling (SOCS)-3 protein expression during intestinal inflammatory states. We have investigated whether these three processes are linked. By assessing the impact of phyto-cannabinoid cannabidiol (CBD), synthetic cannabinoid (ACEA) and endocannabinoid (AEA) on autophagosome formation, we explored whether these actions were responsible for cyclic SOCS3 protein levels. Our findings show that all three cannabinoids induce autophagy in a dose-dependent manner in fully differentiated CaCo2 cells, a model of mature intestinal epithelium. ACEA and AEA induced canonical autophagy, which was cannabinoid receptor (CB)-1 mediated. In contrast, CBD was able to bypass both the CB1 receptor and the canonical pathway to induce autophagy, albeit to a lesser extent. Functionally, all three cannabinoids reduced SOCS3 protein expression, which was reversed by blocking both early and late autophagy. In conclusion, the regulatory protein, SOCS3, is itself regulated by autophagy and cannabinoids play a role in this process, which could be important when considering therapeutic applications for the cannabinoids in inflammatory conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/24833710

Getting High on the Endocannabinoid System

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“The endogenous cannabinoid system—named for the plant that led to its discovery—is one of the most important physiologic systems involved in establishing and maintaining human health.

Endocannabinoids and their receptors are found throughout the body: in the brain, organs, connective tissues, glands, and immune cells. With its complex actions in our immune system, nervous system, and virtually all of the body’s organs, the endocannabinoids are literally a bridge between body and mind.

By understanding this system, we begin to see a mechanism that could connect brain activity and states of physical health and disease.

…either stimulating or inhibiting the endocannabinoid system could have beneficial effects.

The most direct route of THC administration is by smoking marijuana or other forms of cannabis. Yet purified, FDA-approved medicinal preparations of THC are available in pill form… Why not just take a pill? There are several reasons that some patients prefer puffing over swallowing. One quantitatively minor factor is potential lethality.

It is possible to get a fatal overdose by swallowing too many THC pills at once, whereas documented evidence of death simply from smoking too much cannabis does not seem to exist.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997295/

The cannabinoid delta(9)-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells.

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“…there is considerable interest in therapeutics that can modulate survival signalling pathways and target cancer cells for death. There is emerging evidence that cannabinoids, especially Delta(9)-tetrahydrocannabinol (THC), may represent novel anticancer agents, due to their ability to regulate signalling pathways critical for cell growth and survival.

Here, we report that CB1 and CB2 cannabinoid receptors are expressed in human colorectal adenoma and carcinoma cells, and show for the first time that THC induces apoptosis in colorectal cancer cells…

The use of THC, or selective targeting of the CB1 receptor, may represent a novel strategy for colorectal cancer therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/17583570

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