Spontaneous involution of pediatric low-grade gliomas: high expression of cannabinoid receptor 1 (CNR1) at the time of diagnosis may indicate involvement of the endocannabinoid system.

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“Pediatric low-grade gliomas (P-LGG) consist of a mixed group of brain tumors that correspond to the majority of CNS tumors in children.

Notably, they may exhibit spontaneous involution after subtotal surgical removal (STR). In this study, we investigated molecular indicators of spontaneous involution in P-LGG.

CONCLUSIONS:

The P-LGG, which remained stable or that presented spontaneous involution after STR, showed significantly higher CNR1 expression at the time of diagnosis.

We hypothesize that high expression levels of CNR1 provide tumor susceptibility to the antitumor effects of circulating endocannabinoids like anandamide, resulting in tumor involution.

This corroborates with reports suggesting that CNR1 agonists and activators of the endocannabinoid system may represent therapeutic opportunities for children with LGG.

We also suggest that CNR1 may be a prognostic marker for P-LGG.

This is the first time spontaneous involution of P-LGG has been suggested to be induced by endocannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/27613640

[Progress in study on endocannabinoids and cannabinoid receptors in the treatment for neuropathic pain].

 

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“Endocannabinoids and cannabinoid receptors are expressed in various central pain modulation regions. They maintain in dynamic changes in the expression level and distribution under different pathological and physiological conditions. These changes possess advantage as well as disadvantage. Exogenous administration of endocannabinoids exerts analgesic effect in different pain models, which is mainly mediated by the cannabinoid CB1 and CB2 receptors. Inhibition of enzymes for degrading endocannabinoids in different pain models also shows analgesic effect due to the increased local levels of endocannabinoids.”

Interaction between Cannabinoid System and Toll-Like Receptors Controls Inflammation.

 

 

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“Since the discovery of the endocannabinoid system consisting of cannabinoid receptors, endogenous ligands, and biosynthetic and metabolizing enzymes, interest has been renewed in investigating the promise of cannabinoids as therapeutic agents.

Abundant evidence indicates that cannabinoids modulate immune responses.

An inflammatory response is triggered when innate immune cells receive a danger signal provided by pathogen- or damage-associated molecular patterns engaging pattern-recognition receptors.

Toll-like receptor family members are prominent pattern-recognition receptors expressed on innate immune cells.

Cannabinoids suppress Toll-like receptor-mediated inflammatory responses.

Innate immune cells express cannabinoid receptors and produce endogenous cannabinoids.

Hence, innate immune cells may play a role in regulating endocannabinoid homeostasis, and, in turn, the endocannabinoid system modulates local inflammatory responses.

Studies designed to probe the interaction between the innate immune system and the endocannabinoid system may identify new potential molecular targets in developing therapeutic strategies for chronic inflammatory diseases.

This review discusses the endocannabinoid system and Toll-like receptor family and evaluates the interaction between them.”

http://www.ncbi.nlm.nih.gov/pubmed/27597805

2-Arachidonylglycerol, an endogenous cannabinoid, inhibits tumor necrosis factor-alpha production in murine macrophages, and in mice.

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“2-Arachidonylglycerol (2-AG) inhibits the production in vitro of tumor necrosis factor-alpha (TNF-alpha) by mouse macrophages, as well as in mice. It has no effect on the production of nitric oxide (NO). The effect on TNF-alpha is enhanced when 2-AG is administered together with 2-linoleylglycerol (2-Lino-G) and 2-palmitylglycerol (2-PalmG), an ‘entourage effect’ previously noted in several behavioral and binding assays. 2-AG also suppresses the formation of radical oxygen intermediates.”

Characterization of peripheral cannabinoid receptor expression and clinical correlates in schizophrenia.

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“The relationship between cannabinoid receptor signaling and psychosis vulnerability requires further exploration.

The endocannabinoid signaling system is extensive, with receptors exerting regulatory functions in both immune and central nervous systems.

In the brain, cannabinoid receptors (CBR) directly modulate neurotransmitter systems.

In the peripheral lymphocyte, CBRs mediate cytokine release, with dysregulated cytokine levels demonstrated in schizophrenia.

These results continue to support dysregulation of particular aspects of the endocannabinoid signaling system in participants with schizophrenia selected for the self-reported absence of marijuana abuse/dependence.”

http://www.ncbi.nlm.nih.gov/pubmed/27591408

Dual-Acting Compounds Targeting Endocannabinoid and Endovanilloid Systems-A Novel Treatment Option for Chronic Pain Management.

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“Compared with acute pain that arises suddenly in response to a specific injury and is usually treatable, chronic pain persists over time, and is often resistant to medical treatment.

Because of the heterogeneity of chronic pain origins, satisfactory therapies for its treatment are lacking, leading to an urgent need for the development of new treatments.

The leading approach in drug design is selective compounds, though they are often less effective and require chronic dosing with many side effects.

Herein, we review novel approaches to drug design for the treatment of chronic pain represented by dual-acting compounds, which operate at more than one biological target.

A number of studies suggest the involvement of the cannabinoid and vanilloid receptors in pain.

Interestingly cannabinoid system is in interrelation with other systems that comprise lipid mediators: prostaglandins, produced by COX enzyme.

Therefore, in the present review, we summarize the role of dual-acting molecules (FAAH/TRPV1 and FAAH/COX-2 inhibitors) that interact with endocannabinoid and endovanillinoid systems and act as analgesics by elevating the endogenously produced endocannabinoids and dampening the production of pro-inflammatory prostaglandins.

The plasticity of the endocannabinoid system (ECS) and the ability of a single chemical entity to exert an activity on two receptor systems has been developed and extensively investigated.

Here, we review up-to-date pharmacological studies on compounds interacting with FAAH enzyme together with TRPV1 receptor or COX-2 enzyme respectively.

Multi-target pharmacological intervention for treating pain may lead to the development of original and efficient treatments.”

http://www.ncbi.nlm.nih.gov/pubmed/27582708

Peltatoside Isolated from Annona crassiflora Induces Peripheral Antinociception by Activation of the Cannabinoid System.

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“Peltatoside is a natural compound isolated from leaves of Annona crassiflora Mart., a plant widely used in folk medicine.

This substance is an analogue of quercetin, a flavonoid extensively studied because of its diverse biological activities, including analgesic effects. Besides, a previous study suggested, by computer structure analyses, a possible quercetin-CB1 cannabinoid receptor interaction.

Thus, the aim of this work was to assess the antinociceptive effect of peltatoside and analyze the cannabinoid system involvement in this action.

Our results suggest that this natural substance is capable of inducing analgesia through the activation of peripheral CB1 receptors, involving endocannabinoids in this process.”

http://www.ncbi.nlm.nih.gov/pubmed/27574895

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Endocannabinoid mechanism for orofacial antinociception induced by electroacupuncture in acupoint St36 in rats.

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“This study was conducted with the aim of evaluating whether electroacupuncture (EA) at acupoint St36 could produce antinociception through the activation of an endocannabinoid mechanism.

CONCLUSION:

This study demonstrated for the first time that the CB1 cannabinoid receptor participates in the antinociceptive effect induced by EA.”

http://www.ncbi.nlm.nih.gov/pubmed/27573715

Endocannabinoids inhibit neurogenic inflammation in murine joints by a non-canonical cannabinoid receptor mechanism.

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“Neurogenic inflammation is a local inflammatory response that is driven by the peripheral release of neuropeptides from small diameter afferents which occurs in many organs including joints.

The knee joint has a rich endocannabinoid system which has been shown to decrease acute synovitis.

The aim of this study was to investigate the influence of joint afferents on leukocyte-endothelial interactions within the synovial microcirculation of mice and determine the role of endocannabinoids on this inflammatory response.

These results provide evidence that antidromic stimulation of the mouse saphenous nerve promotes leukocyte rolling within the synovial microcirculation, and that endocannabinoids can attenuate this neurogenic inflammatory response.”

http://www.ncbi.nlm.nih.gov/pubmed/27567396

The gastrointestinal tract – a central organ of cannabinoid signaling in health and disease.

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“In ancient medicine, extracts of the marijuana plant Cannabis sativa were used against diseases of the gastrointestinal (GI) tract.

Today, our knowledge of the ingredients of the Cannabis plant has remarkably advanced enabling us to use a variety of herbal and synthetic cannabinoid (CB) compounds to study the endocannabinoid system (ECS), a physiologic entity that controls tissue homeostasis with the help of endogenously produced CBs and their receptors.

After many anecdotal reports suggested beneficial effects of Cannabis in GI disorders, it was not surprising to discover that the GI tract accommodates and expresses all the components of the ECS.

Cannabinoid receptors and their endogenous ligands, the endocannabinoids, participate in the regulation of GI motility, secretion, and the maintenance of the epithelial barrier integrity.

In addition, other receptors, such as the transient receptor potential cation channel subfamily V member 1 (TRPV1), the peroxisome proliferator-activated receptor alpha (PPARα) and the G-protein coupled receptor 55 (GPR55), are important participants in the actions of CBs in the gut and critically determine the course of bowel inflammation and colon cancer.

PURPOSE:

The following review summarizes important and recent findings on the role of CB receptors and their ligands in the GI tract with emphasis on GI disorders, such as irritable bowel syndrome, inflammatory bowel disease, and colon cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/27561826