Tag Archives: endocannabinoid system

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

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.”

 http://www.ncbi.nlm.nih.gov/pubmed/11011050

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

Interaction between interleukin-1β and type-1 cannabinoid receptor is involved in anxiety-like behavior in experimental autoimmune encephalomyelitis.

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“Mood disorders, including anxiety and depression, are frequently diagnosed in multiple sclerosis (MS) patients, even independently of the disabling symptoms associated with the disease.

Anatomical, biochemical, and pharmacological evidence indicates that type-1 cannabinoid receptor (CB1R) is implicated in the control of emotional behavior and is modulated during inflammatory neurodegenerative diseases such as MS and experimental autoimmune encephalomyelitis (EAE).

We investigated whether CB1R could exert a role in anxiety-like behavior in mice with EAE. We performed behavioral, pharmacological, and electrophysiological experiments to explore the link between central inflammation, mood, and CB1R function in EAE.

Overall, results of the present investigation indicate that synaptic dysfunction linked to CB1R is involved in EAE-related anxiety and motivation-based behavior and contribute to clarify the complex neurobiological mechanisms underlying mood disorders associated to MS.

Collectively, our data contribute to clarify the synaptic and, at least in part, molecular basis of mood disturbances in EAE and, possibly, MS. Understanding the neurobiological underpinning of anxiety-like behavior in EAE mice is of crucial importance to optimize the treatment of mood disturbance in MS and, possibly, other neuroinflammatory diseases.

In this direction, targeting the endocannabinoid system may be a valid therapeutic tool for the treatment of both psychiatric and motor symptoms in MS patients.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009553/

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

The Influence of the CB1 Receptor Ligands on the Schizophrenia-Like Effects in Mice Induced by MK-801.

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“A growing body of psychiatric research has emerged, focusing on the role of endocannabinoid system in psychiatric disorders.

For example, the endocannabinoid system, via cannabinoid CB (CB1 and CB2) receptors, is able to control the function of many receptors, such as N-methyl-D-aspartate (NMDA) receptors connected strictly with psychosis or other schizophrenia-associated symptoms.

The aim of the present research was to investigate the impact of the CB1 receptor ligands on the symptoms typical for schizophrenia.

The present findings confirm that endocannabinoid system is able to modify a variety of schizophrenia-like responses, including the cognitive disturbances and hyperlocomotion in mice.

Antipsychotic-like effects induced by CB1 receptor antagonist, obtained in our research, confirm the potential effect of CB1 receptor blockade and could have important therapeutic implications on clinical settings, in the future.”

http://www.ncbi.nlm.nih.gov/pubmed/27577742

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

Cannabinoid 2 receptor is a novel anti-inflammatory target in experimental proliferative vitreoretinopathy.

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“Proliferative vitreoretinopathy (PVR) can develop after ocular trauma or inflammation and is a common complication of surgery to correct retinal detachment.

Currently, there are no pharmacological treatments for PVR.

Cannabinoids acting at cannabinoid 2 receptor (CB2R) can decrease inflammation and fibrosis.

The objective of this study was to examine the anti-inflammatory actions of CB2R as a candidate novel therapeutic target in experimental PVR.

In conclusion, our results indicate that intervention at early stage PVR with CB2R agonists reduces ocular inflammation and disease severity.

CB2R may represent a therapeutic target to prevent PVR progression and vision loss.”

http://www.ncbi.nlm.nih.gov/pubmed/27569993