Tag Archives: cannabinoid receptors

(-)-β-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis.

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“(-)-β-caryophyllene (BCP), a cannabinoid receptor type 2 (CB2)-selective phytocannabinoid, has already been shown in precedent literature to exhibit both anti-inflammatory and analgesic effects in mouse models of inflammatory and neuropathic pain.

Herein, we endeavored to investigate the therapeutic potential of BCP on experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). Furthermore, we sought to demonstrate some of the mechanisms that underlie the modulation BCP exerts on autoimmune activated T cells, the pro-inflammatory scenery of the central nervous system (CNS), and demyelination.

Our findings demonstrate that BCP significantly ameliorates both the clinical and pathological parameters of EAE. In addition, data hereby presented indicates that mechanisms underlying BCP immunomodulatory effect seems to be linked to its ability to inhibit microglial cells, CD4+ and CD8+ T lymphocytes, as well as protein expression of pro-inflammatory cytokines. Furthermore, it diminished axonal demyelination and modulated Th1/Treg immune balance through the activation of CB2 receptor.

Altogether, our study represents significant implications for clinical research and strongly supports the effectiveness of BCP as a novel molecule to target in the development of effective therapeutic agents for MS.” https://www.ncbi.nlm.nih.gov/pubmed/28368293

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”  http://www.ncbi.nlm.nih.gov/pubmed/23138934

Post-sensitization treatment with rimonabant blocks the expression of cocaine-induced behavioral sensitization and c-Fos protein in mice.

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“CB1 receptor antagonists have been shown to prevent acute and long-term behavioral effects of cocaine.

Here we evaluate the effectiveness of the CB1 receptor antagonist rimonabant to modify sensitized responses to cocaine.

Our findings add to the evidence that drugs targeting CB1 receptors are good candidates for the treatment of cocaine abuse and provide further insights into the mechanisms underlying endocannabinoid signaling within the brain reward system in the context of cocaine abuse.”

https://www.ncbi.nlm.nih.gov/pubmed/28366798

[Role of cannabinoid receptor 1-mediated synaptic plasticity in neuropathic pain and associated depression].

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“Neuropathic pain is a class of pain caused by an injury or diseases of the somatosensory system and characterized by spontaneous pain, allodynia, and hyperalgesia. It is well established that central sensitization is one of the key mechanisms underlying the development and maintenance of neuropathic pain. Cannabinoid receptor 1 (CB1R) of endocannabinoid system modulates synaptic transmission, regulates synaptic plasticity, inhibits central sensitization, and thus attenuates neuropathic pain. Recent studies have shown that activation of CB1R also involves in the relief of neuropathic pain-induced depression.” https://www.ncbi.nlm.nih.gov/pubmed/28364110

The effect of cannabinoid receptor 1 blockade on hepatic free fatty acid profile in mice with nonalcoholic fatty liver disease.

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“We used rimonabant to investigate the role of CB1 receptor on hepatic FFAs profile during NAFLD. Male mice C57BL/6 were divided into: control group fed with control diet 20 weeks (C; n=6); group fed with HFD 20 weeks (HF; n=6); group fed with control diet and treated with rimonabant after 18 weeks (R; n=9); group fed with HFD and treated with rimonabant after 18 weeks (HFR; n=10). Rimonabant (10mg/kg) was administered daily to HFR and R group by oral gavage. Rimonabant decreased liver palmitic acid proportion in HFR group compared to HF group (p<0.05). Liver stearic and oleic acid proportions were decreased in R group compared to control (p<0.01 respectively). Rimonabant increased liver linoleic and arachidonic acid proportions in HFR group compared to HF group (p<0.01 respectively). CB1 blockade may be useful in the treatment of HFD-induced NAFLD due to modulation of plasma lipid and hepatic FFA profile.”  https://www.ncbi.nlm.nih.gov/pubmed/28363784

http://www.sciencedirect.com/science/article/pii/S0009308417300063

Genetic or pharmacological depletion of cannabinoid CB1 receptor protects against dopaminergic neurotoxicity induced by methamphetamine in mice.

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“Accumulating evidence suggests that cannabinoid ligands play delicate roles in cell survival and apoptosis decisions, and that cannabinoid CB1 receptors (CB1R) modulate dopaminergic function.

However, the role of CB1R in methamphetamine (MA)-induced dopaminergic neurotoxicity in vivo remains elusive.

Multiple high doses of MA increased phospho-ERK and CB1R mRNA expressions in the striatum of CB1R (+/+) mice. These increases were attenuated by CB1R antagonists (i.e., AM251 and rimonabant), an ERK inhibitor (U0126), or dopamine D2R antagonist (sulpiride).

CB1R agonist-induced toxic effects were significantly attenuated by CB1R knockout, CB1R antagonists or PKCδ knockout.

Therefore, our results suggest that interaction between D2R, ERK and CB1R is critical for MA-induced dopaminergic neurotoxicity and that PKCδ mediates dopaminergic damage induced by high-doses of CB1R agonist.”

https://www.ncbi.nlm.nih.gov/pubmed/28363605

Comparative antinociceptive effect of arachidonylcyclopropylamide, a cannabinoid 1 receptor agonist & lignocaine, a local anaesthetic agent, following direct intrawound administration in rats.

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“Treatment of inflammatory pain with opioids is accompanied by unpleasant and, at times, life-threatening side effects.

Cannabis produces antinociception as well as psychotropic effects. It was hypothesized that peripheral cannabinoid receptors outside the central nervous system could be selectively activated for relief of pain.

This study was undertaken to measure the antinociceptive effect of type 1 cannabinoid receptor (CB1r) agonist arachidonylcyclopropylamide (ACPA) in a rat model of inflammatory pain after intrawound administration and the effects were compared with lignocaine.

Lignocaine attenuated evoked pain behaviour whereas ACPA decreased guarding score. This difference was likely due to blockade of sodium ion channels and the activation of peripheral CB1r, respectively. Central side effects were absent after ACPA treatment. Further studies need to be done to assess the effect of ACPA treatment in clinical conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/28361827

Activation of CB1 receptors by 2-arachidonoylglycerol attenuates vasoconstriction induced by U46619 and angiotensin II in human and rat pulmonary arteries.

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“Recent evidence suggests that endocannabinoids acting via cannabinoid CB1 receptors may modulate vascular responses of various vasoconstrictors in the rodent systemic vasculature.

The aim of the study was to investigate whether endocannabinoids modulate the contractile responses evoked by a thromboxane A2 analog (U46619), angiotensin II (Ang II), serotonin (5-HT) and phenylephrine which stimulate distinct Gq/11-protein coupled receptors (TP, AT1, 5-HT2 and α1-adrenergic) in isolated endothelium-intact human (hPAs) and rat pulmonary arteries (rPAs).

The present study shows the protective interaction between the endocannabinoid system and vasoconstriction to U46619 and Ang II in the human and rat pulmonary circulation. U46619 and Ang II may stimulate rapid endothelial release of endocannabinoids (mainly 2-arachidonoylglycerol), leading to CB1 receptor-dependent and/or -independent vasorelaxation, which in the negative feedback mechanism reduces later agonists-induced vasoconstriction.” https://www.ncbi.nlm.nih.gov/pubmed/28356298

http://ajpregu.physiology.org/content/early/2017/03/27/ajpregu.00324.2016

Regulation of Cell Surface CB2 Receptor during Human B Cell Activation and Differentiation.

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“Cannabinoid receptor type 2 (CB2) is the primary receptor pathway mediating the immunologic consequences of cannabinoids.

We recently reported that human peripheral blood B cells express CB2 on both the extracellular membrane and at intracellular sites, where-as monocytes and T cells only express intracellular CB2. To better understand the pattern of CB2 expression by human B cells, we examined CD20+ B cells from three tissue sources.

Both surface and intracellular expression were present and uniform in cord blood B cells, where all cells exhibited a naïve mature phenotype (IgD+/CD38Dim). While naïve mature and quiescent memory B cells (IgD–/CD38–) from tonsils and peripheral blood exhibited a similar pattern, tonsillar activated B cells (IgD–/CD38+) expressed little to no surface CB2.

We hypothesized that regulation of the surface CB2 receptor may occur during B cell activation. Consistent with this, a B cell lymphoma cell line known to exhibit an activated phenotype (SUDHL-4) was found to lack cell surface CB2 but express intracellular CB2.

Furthermore, in vitro activation of human cord blood resulted in a down-regulation of surface CB2 on those B cells acquiring the activated phenotype but not on those retaining IgD expression. Using a CB2 expressing cell line (293 T/CB2-GFP), confocal microscopy confirmed the presence of both cell surface expression and multifocal intracellular expression, the latter of which co-localized with endoplasmic reticulum but not with mitochondria, lysosomes, or nucleus.

Our findings suggest a dynamic multi-compartment expression pattern for CB2 in B cells that is specifically modulated during the course of B cell activation.”

 https://www.ncbi.nlm.nih.gov/pubmed/28364261

In vivo TSPO and cannabinoid receptor type 2 availability early in post-stroke neuroinflammation in rats: a positron emission tomography study.

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“Upregulated levels of 18-kDa translocator proteins (TSPO) and type 2 endocannabinoid receptors (CB2) are considered to reflect different aspects of microglia-related neuroinflammatory responses in the brain. Relative to the increase in the TSPO expression that occurs slightly later during neuroinflammation in a proinflammatory fashion, CB2 activation is considered to relate to the neuroprotective responses that occurs predominantly at an early stage of brain disorders. These findings, however, were deduced from studies with different animal samples under different experimental settings. Here, we aimed to examined the differences in TSPO binding and CB2 availability at an early stage of stroke in the same animal using positron emission tomography (PET).

CONCLUSIONS:

The present results provide in vivo evidence of different responses of microglia occurring in the acute state of stroke. The use of the CB2 tracer [11C]NE40 allows us to evaluate the roles played by the neuroprotective aspect of microglia in acute neuroinflammatory processes.” https://www.ncbi.nlm.nih.gov/pubmed/28356120

https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-017-0851-4

It’s Oral, Head & Neck Cancer Awareness Month. Please Be Aware.

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“Oral, Head & Neck Cancer Awareness Month. While smoking and tobacco use are still major risk factors, the fastest growing segment of oral cancer patients is young, healthy, nonsmoking individuals due to the connection to the HPV virus. We cannot stop this virus from spreading; our only hope to save lives is with professional involvement and public awareness.”  http://oralcancerfoundation.org/events/oral-head-neck-cancer-awareness-month/

“Oral Sex Linked to Rise in Oral Cancers”  https://www.roswellpark.org/cancertalk/201304/oral-sex-linked-rise-oral-cancers

“Role of human papilloma virus in the oral carcinogenesis”  https://www.ncbi.nlm.nih.gov/pubmed/19542661                                                           “A causal role for human papillomavirus in head and neck cancer.”  https://www.ncbi.nlm.nih.gov/pubmed/15135592/

“Bogarting that joint might decrease oral hpv among cannabis users. The development of oral cancer is not a result of smoking cannabis per se; rather, it is hypothesized to be a result of contracting hpv through various forms of sharing and passing joints and other smoking apparatuses. Therefore, it is hypothesized that bogarting (and not passing) joints might decrease oral hpv among cannabis smokers.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794675/

“Additive found in toothpaste and food products could cause cancer, say scientists” http://www.independent.co.uk/news/science/toothpaste-additive-e171-titanium-dioxide-food-products-cancer-cause-scientists-a7541956.html

“Mouthwash And Poor Dental Hygiene May Up The Risk Of Oral Cancer”  http://www.npr.org/sections/health-shots/2014/04/08/300257396/mouthwash-and-poor-dental-hygiene-may-up-the-risk-of-oral-cancer

“Gum Disease Linked to Risk of Oral Cancer Causing Virus”  https://www.bloomberg.com/news/articles/2013-08-21/gum-disease-linked-to-risk-of-oral-cancer-causing-virus

“ROUGH TEETH AND RUBBING DENTURES MAY BE LINKED TO ORAL CANCER” http://www.managedhealthcareconnect.com/content/rough-teeth-and-rubbing-dentures-may-be-linked-oral-cancer

“Unhealthy lifestyles blamed for sharp rise in mouth cancer cases”  http://www.itv.com/news/2016-11-25/bad-habits-linked-to-soaring-rates-of-mouth-cancer/

“Type of food and risk of oral cancer. To reduce the risk of oral and pharyngeal cancer, especially squamous cell carcinoma, the most common oral cancer, diet must be optimized, primarily to reduce calorie intake, monounsaturated fat, and red or processed meat. Consumption of fruits, vegetables, and cereals, which are the major source of vitamins and fiber, should be adequate in the daily diet. Optimal levels of daily allowance of micronutrients like vitamin C, E, antioxidants, zinc, beta-carotene, and folate are effective in prevention of oral cancer. Consumption of fried or broiled foods and employment of microwave cooking, because of formation of heterocyclic amines, must be avoided because of increasing risks of oral cancer including the salivary gland tumors.”  https://www.ncbi.nlm.nih.gov/pubmed/17367228

“Coffee consumption associated with reduced risk of oral cancer: a meta-analysis”  http://www.sciencedirect.com/science/article/pii/S2212440315013656

“Tobacco and alcohol use are among the strongest risk factors for oral cavity and oropharyngeal cancers.” https://www.cancer.org/cancer/oral-cavity-and-oropharyngeal-cancer/causes-risks-prevention/risk-factors.html

“Marijuana use on its own does not merit definitive oral cancer development, according to research. In fact, cannabis also contains cannabinoids, such as THC, which contain anticancer properties. Some of these anticancer properties include the slowing of the inflammatory arm of the immune system designed to slow free-radical growths. Some researchers link medicinal marijuana to these anticancer properties.” http://www.dentistryiq.com/articles/2014/04/should-marijuana-users-be-worried-that-smoking-causes-oral-cancer.html

“Marijuana has been used in herbal remedies for centuries. More recently, scientists reported that THC and other cannabinoids such as CBD slow growth and/or cause death in certain types of cancer cells.” http://www.cancer.org/treatment/treatmentsandsideeffects/physicalsideeffects/chemotherapyeffects/marijuana-and-cancer

“Cannabis has been shown to kill cancer cells in the laboratory. Cannabinoids appear to kill tumor cells but do not affect their nontransformed counterparts and may even protect them from cell death.” http://www.cancer.gov/about-cancer/treatment/cam/patient/cannabis-pdq#section/all

“Marijuana Kills Cancer Cells, Admits The U.S. National Cancer Institute” http://naturalsociety.com/marijuana-kills-cancer-cells-admits-the-u-s-national-cancer-institute/

“US government says cannabis kills cancer cells”  http://www.telegraph.co.uk/news/worldnews/northamerica/usa/11820620/US-government-says-cannabis-kills-cancer-cells.html

“US government finally admits that cannabis kills cancer cells”  http://www.mirror.co.uk/news/world-news/government-finally-admits-cannabis-kills-6303176

“Review of Various Herbal Supplements as Complementary Treatments for Oral Cancer. Diet changes, supplementation with antioxidants, high-dose vitamin C therapy, and cannabinoid use have been suggested to decrease cancer cell replication and increase chance of remission.”  https://www.ncbi.nlm.nih.gov/pubmed/26863913

“Cannabinoids Offer Some Hope for Oral Cancer Pain”  https://www.practicalpainmanagement.com/meeting-summary/cannabinoids-offer-some-hope-oral-cancer-pain

“Cannabinoids Attenuate Cancer Pain and Proliferation in a Mouse Model.  Our results suggest that systemic administration of cannabinoids decease oral cancer pain. Our findings suggest a direct role for cannabinoid mechanisms in oral cancer pain and proliferation. The systemic administration of cannabinoid receptor agonists may have important therapeutic implications wherein cannabinoid receptor agonists may reduce morbidity and mortality of oral cancer. The present findings suggest that cannabinoid treatment may be a promising alternative therapy for oral cancer pain management.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3099480/

“Cannabinoids Inhibit Cellular Respiration of Human Oral Cancer Cells. The primary cannabinoids, Δ9-tetrahydrocannabinol (Δ9-THC) and Δ8-tetrahydrocannabinol (Δ8-THC) are known to disturb the mitochondrial function and possess antitumor activities. These observations prompted us to investigate their effects on the mitochondrial O2 consumption in human oral cancer cells (Tu183). This epithelial cell line overexpresses bcl-2 and is highly resistant to anticancer drugs. A rapid decline in the rate of respiration was observed when Δ9-THC or Δ8-THC was added to the cells. These results show the cannabinoids are potent inhibitors of Tu183 cellular respiration and are toxic to this highly malignant tumor.” https://www.karger.com/Article/Abstract/312686

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“CANNABINOIDS INHIBIT ORAL CANCER CELLS”  https://pharmotech.ch/cannabinoids-inhibit-oral-cancer-cells/

“Evaluation of cannabinoid CB1 and CB2 receptors expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients’ survival. The present study provides evidence that CB1R and CB2R may play a role in the pathophysiological aspects of the mobile tongue squamous cell carcinoma (SCC) and even each molecule may constitute a potential target for the development of novel anti-cancer drugs for this type of malignancy.” https://www.ncbi.nlm.nih.gov/pubmed/26459312

“Review: cannabidiol may be beneficial for oral mucositis. The researchers found evidence that oxidative stress control could prevent and relieve oral mucositis. Cannabidiol was found to be safe to use and demonstrated antioxidant, anti-inflammatory, and analgesic properties,” https://medicalxpress.com/news/2017-02-cannabidiol-beneficial-oral-mucositis.html

“Salivary bacteria linked to oral cancers”  http://middleeast.thelancet.com/journals/lanonc/article/PIIS1470-2045(05)70266-7/abstract

“Antibacterial Cannabinoids from Cannabis sativa: A Structure−Activity Study”  http://pubs.acs.org/doi/abs/10.1021/np8002673

“Targeting Id1 reduces proliferation and invasion in aggressive human salivary gland cancer cells.  Id1 suppression could represent a novel and effective approach for the treatment of salivary gland cancer.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639030/

“Suppression of invasion and metastasis in aggressive salivary cancer cells through targeted inhibition of ID1 gene expression.”  https://www.ncbi.nlm.nih.gov/pubmed/27087608

“Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells. CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells.  Moreover, reducing Id-1 expression with cannabinoids could also provide a therapeutic strategy for the treatment of additional aggressive cancers because Id-1 expression was found to be up-regulated during the progression of almost all types”  http://mct.aacrjournals.org/content/6/11/2921.long

“Anticancer effects of anandamide on head and neck squamous cell carcinoma cells via the production of receptor-independent reactive oxygen species.”  https://www.ncbi.nlm.nih.gov/pubmed/24797795

“The endocannabinoid system and cancer: therapeutic implication. Many in vitro and in vivo studies have shown that cannabinoids are efficacious in reducing cancer progression (i.e. inhibition of tumour growth and metastases as well as induction of apoptosis and other anti-cancer properties) in breast, prostate and bone cancer. Although this review focuses on these three types of cancer, activation of the endocannabinoid signalling system produces anti-cancer effects in other types of cancer.” http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01327.x/full

“Medical marijuana use in head and neck squamous cell carcinoma patients treated with radiotherapy. The purpose of the study was to better understand why patients with history of head and neck cancer (HNC) treated with radiotherapy are using medical marijuana (MM). HNC patients report MM use to help with long-term side effects of radiotherapy.” http://www.ncbi.nlm.nih.gov/pubmed/27005465

“Head and neck cancer among marijuana users: A meta-analysis of matched case–control studies. No association between lifetime marijuana use and the development of head and neck cancer was found.”  http://www.aobjournal.com/article/S0003-9969(15)30041-8/abstract

“A Population-based Case-Control Study of Marijuana Use and Head and Neck Squamous Cell Carcinoma. Our study suggests that moderate marijuana use is associated with reduced risk of head and neck cancer (HNSCC). In fact, many of these studies reported non-significant protective estimates of effect, consistent with a possible anticarcinogenic action of cannabinoids.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2812803/

“Smoking Marijuana Regularly May Reduce Risk of Some Neck, Head Cancers” http://www.foxnews.com/story/2009/08/26/smoking-marijuana-regularly-may-reduce-risk-some-neck-head-cancers.html

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