Tag Archives: cannabinoid receptors

Activation of endocannabinoid system in the rat basolateral amygdala improved scopolamine-induced memory consolidation impairment.

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“The current study was designed to examine the involvement of cannabinoid CB1 receptors in the basolateral amygdala (BLA) in scopolamine-induced memory impairment in adult male Wistar rats.

In view of the known actions of the drugs used, the present data pointed to the involvement of the BLA CB1 receptors in scopolamine-induced memory consolidation impairment.

Furthermore, it seems that a functional interaction between the BLA endocannabinoid and cholinergic muscarinic systems may be critical for memory formation.”

http://www.ncbi.nlm.nih.gov/pubmed/27230394

“The most dangerous drug in the world: ‘Devil’s Breath’ chemical from Colombia can block free will, wipe memory and even kill. Scopolamine often blown into faces of victims or added to drinks. Within minutes, victims are like ‘zombies’ – coherent, but with no free will. Drug is made from borrachero tree, which is common in Colombia”  http://www.dailymail.co.uk/news/article-2143584/Scopolamine-Powerful-drug-growing-forests-Colombia-ELIMINATES-free-will.html

“Activation of endocannabinoid system in the rat basolateral amygdala improved scopolamine-induced memory consolidation impairment.”  http://www.ncbi.nlm.nih.gov/pubmed/27230394

Cannabinoids inhibit fibrogenesis in diffuse systemic sclerosis fibroblasts.

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Rheumatology

“Recently, it has also been demonstrated that the pleiotropic cannabinoid system is involved in both liver and pancreatic fibrosis. Furthermore, cannabinoids may play a pro- or anti-fibrogenic role depending on their interaction with CB1r or CB2r.

This raises the possibility that pharmacologic modulation of the endocannabinoid system could be a target to limit tissue damage in pathologic fibrosis.

It has been demonstrated that the endocannabinoid system is up-regulated in pathologic fibrosis and that modulation of the cannabinoid receptors might limit the progression of uncontrolled fibrogenesis.

Both CB1 and CB2 receptors were over-expressed in dcSSc fibroblasts compared with healthy controls.

Our preliminary findings suggest that cannabinoids are provided with an anti-fibrotic activity, thereby possibly representing a new class of agents targeting fibrosis diseases.”

http://rheumatology.oxfordjournals.org/content/48/9/1050.long

The effect of cannabinoids on dinitrofluorobenzene-induced experimental asthma in mice.

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“Cannabinoids have anti-inflammatory effects and can produce bronchodilation in the airways.

We have investigated the effects of cannabinoids on tracheal hyperreactivity and airway inflammation in dinitrofluorobenzene (DNFB)-induced experimental non-atopic asthma in mice.

These results show that cannabinoid CB1 receptor agonist can prevent tracheal hyperreactivity to 5-HT in DNFB-induced non-atopic asthma in mice.”

http://www.ncbi.nlm.nih.gov/pubmed/27216000

Cannabinoid receptor 2 (CB2) agonists and antagonists: a patent update.

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“Modulation of the CB2 receptor is an interesting approach for pain and inflammation, arthritis, addictions, neuroprotection, and cancer, among other possible therapeutic applications, and is devoid of central side effects.

Structural diversity of CB2 modulator scaffolds characterized the patent literature.

Several CB2 agonists reached clinical Phase II for pain management and inflammation.

Other therapeutic applications need to be explored such as neuroprotection and/or neurodegeneration.”

http://www.ncbi.nlm.nih.gov/pubmed/27215781

Anti-inflammatory and antioxidant effects of a combination of cannabidiol and moringin in LPS-stimulated macrophages.

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“Inflammatory response plays an important role in the activation and progress of many debilitating diseases. Natural products, like cannabidiol, a constituent of Cannabis sativa, and moringin, an isothiocyanate obtained from myrosinase-mediated hydrolysis of the glucosinolate precursor glucomoringin present in Moringa oleifera seeds, are well known antioxidants also endowed with anti-inflammatory activity.

This is due to a covalent-based mechanism for ITC, while non-covalent interactions underlie the activity of CBD. Since these two mechanisms are distinct, and the molecular endpoints are potentially complementary, we investigated in a comparative way the protective effect of these compounds alone or in combination on lipopolysaccharide-stimulated murine macrophages.

Our results show that the cannabidiol (5μM) and moringin (5μM) combination outperformed the single constituents that, at this dosage had only a moderate efficacy on inflammatory (Tumor necrosis factor-α, Interleukin-10) and oxidative markers (inducible nitric oxide synthase, nuclear factor erythroid 2-related factor 2, nitrotyrosine). Significant upregulation of Bcl-2 and downregulation of Bax and cleaved caspase-3 was observed in cells treated with cannabidiol-moringin combination.

Treatment with the transient receptor potential vanilloid receptor 1 antagonist was detrimental for the efficacy of cannabidiol, while no effect was elicited by cannabinoid receptor 1 and cannabinoid receptor 2 antagonists. None of these receptors was involved in the activity of moringin.

Taken together, our in vitro results testify the anti-inflammatory, antioxidative, and anti-apoptotic effects of the combination of cannabidiol and moringin.”

http://www.ncbi.nlm.nih.gov/pubmed/27215129

Stimulation of brain glucose uptake by cannabinoid CB2 receptors and its therapeutic potential in Alzheimer’s disease

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“Brain disorders, including Alzheimer’s disease (AD), often involve specific early alterations in the metabolism of glucose in the brain.

The idea of alleviating symptoms of dementia by boosting cerebral energy metabolism has been toyed with for decades, yet safe pharmacological agents with well characterized mechanism of action are still lacking.

In this sense, we have investigated here the local cerebral glucoregulatory potential of the endocannabinoid system in rodents.

Cannabinoid CB2 receptors (CB2Rs) are emerging as important therapeutic targets in brain disorders that typically involve neurometabolic alterations.

Together, these results reveal a novel general glucoregulatory role for CB2Rs in the brain, raising therapeutic interest in CB2R agonists as nootropic agents.

In conclusion, the present results provide the first direct pharmacological evidence in vitroand in vivo of a role of CB2R in central glucoregulation.

Additionally, we found that glucoregulation by endogenous CB2R signalling is negatively affected by β-amyloidosis, thought to be the first pathological step in AD.

Therefore, it would be interesting to perform further studies to define how CB2R mediated glucoregulation contributes to the recently discovered therapeutic potential of CB2R agonists in animal models of AD”

http://www.sciencedirect.com/science/article/pii/S0028390816300879

Novel role of cannabinoid receptor 2 in inhibiting EGF/EGFR and IGF-I/IGF-IR pathways in breast cancer.

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Image result for Oncotarget.“Breast cancer is the second leading cause of cancer deaths among women.

Cannabinoid receptor 2 (CNR2 or CB2) is an integral part of the endocannabinoid system.

Although CNR2 is highly expressed in the breast cancer tissues as well as breast cancer cell lines, its functional role in breast tumorigenesis is not well understood.

We observed that estrogen receptor-α negative (ERα-) breast cancer cells highly express epidermal growth factor receptor (EGFR) as well as insulin-like growth factor-I receptor (IGF-IR). We also observed IGF-IR upregulation in ERα+ breast cancer cells.

In addition, we found that higher CNR2 expression correlates with better recurrence free survival in ERα- and ERα+ breast cancer patients.

Our studies showed that CNR2 activation inhibited EGF and IGF-I-induced migration and invasion of ERα+ and ERα- breast cancer cells.

In conclusion, we show that CNR2 activation suppresses breast cancer through novel mechanisms by inhibiting EGF/EGFR and IGF-I/IGF-IR signaling axes.”

http://www.ncbi.nlm.nih.gov/pubmed/27213582

Cannabinoid receptor 2 as a potential therapeutic target in rheumatoid arthritis

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“Some of cannabinoids, which are chemical compounds contained in marijuana, are immunosuppressive.

One of the receptors, CB receptor 1 (CB1), is expressed predominantly by the cells in the central nervous system, whereas CB receptor 2 (CB2) is expressed primarily by immune cells.

Theoretically, selective CB2 agonists should be devoid of psychoactive effects.

In this study, we investigated therapeutic effects of a selective CB2 agonist on arthritis.

The present study suggests that a selective CB2 agonist could be a new therapy for RA that inhibits production of inflammatory mediators from FLS, and osteoclastogenesis.

This is the first report of therapeutic effect of a selective CB2 agonist on CIA.

Although the effect was mild, optimization of dosage and/or treatment protocol might enhance the effect.

Perhaps, more potent selective CB2agonists might solve this problem.

Cannabinoids are pharmacologically active components of Cannabis sativa.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243420/

The synthetic cannabinoid WIN55,212-2 mesylate decreases the production of inflammatory mediators in rheumatoid arthritis synovial fibroblasts by activating CB2, TRPV1, TRPA1 and yet unidentified receptor targets

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“Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by joint inflammation and cartilage destruction.

In this study we assessed the ability of WIN to modulate cytokine and MMP-3 production in SFs over a wide concentration range and identified specific receptor targets that mediate the effects of this synthetic cannabinoid.

The synthetic cannabinoid WIN in low concentrations exhibits anti-inflammatory effects in synovial fibroblasts independent of CB1 and CB2 while CB2 and yet unidentified receptor targets are responsible for WIN effects in micromolar concentrations.

Our results indicate a TRPV1/TRPA1 dependent mechanism of SF regulation that might be coupled to cellular energy status and calcium content.

In this report we demonstrated anti-inflammatory effects of the synthetic cannabinoid WIN in low and high concentrations.

Furthermore, this study demonstrated anti-inflammatory effects via modulation of TRP channels by WIN. Together, inactivation of TRPs and activation of cannabinoid receptors might also reduce the sensation of pain, which further underlines the potential of WIN in the treatment of chronic inflammation.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858820/

Synthetic cannabinoid receptor agonists and antagonists: implication in CNS disorders.

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“Since the discovery of the cannabinoid receptors, numerous studies associate the endocannabinoid system with several physiological and pathological processes including cancer, appetite, fertility, memory, neuropathic and inflammatory pain, obesity, and neurodegenerative diseases.

Over the last two decades, several researches have been dedicated extensively on the cannabinoid receptors ligands since the direct activation of cannabinoid receptors results in several beneficial effects, in the brain and in the periphery.

During past years, cannabinoid CB1 and CB2 receptor ligands from plants or lab were rapidly developed and then various new structures were reported to be cannabinoids.

The CB1 and CB2 receptor ligands offer several therapeutic opportunities for several CNS-related diseases.

Based on the scientific literature, this review provides an overview of CB1 and CB2 receptor synthetic ligands obtained from drug research and in particular those synthesized for therapeutic purposes and potential clinical applications for central nervous system disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/27193072