Cannabinoid receptor 2 augments eosinophil responsiveness and aggravates allergen-induced pulmonary inflammation in mice.

Posted on February 8, 2016 by David

“Accumulation of activated eosinophils in tissue is a hallmark of allergic inflammation.

The endocannabinoid 2-arachidonoylglycerol (2-AG) has been proposed to elicit eosinophil migration in a CB₂ receptor/G_i/o -dependent manner.

Here we explored the direct contribution of specific CB₂ receptor activation to human and mouse eosinophil effector function in vitro and in vivo.

Our data indicate that CB₂ may directly contribute to the pathogenesis of eosinophil-driven diseases. Moreover, we provide new insights into the molecular mechanisms underlying the CB₂ -mediated priming of eosinophils. Hence, antagonism of CB₂ receptors may represent a novel pharmacological approach for the treatment of allergic inflammation and other eosinophilic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26850094

Expression and Function of the Endocannabinoid System in the Retina and the Visual Brain.

Posted on February 4, 2016 by David

“Endocannabinoids are important retrograde modulators of synaptic transmission throughout the nervous system.

Cannabinoid receptors are seven transmembrane G-protein coupled receptors favoring Gi/o protein. They are known to play an important role in various processes, including metabolic regulation, craving, pain, anxiety, and immune function.

In the last decade, there has been a growing interest for endocannabinoids in the retina and their role in visual processing.

The purpose of this review is to characterize the expression and physiological functions of the endocannabinoid system in the visual system, from the retina to the primary visual cortex, with a main interest regarding the retina, which is the best-described area in this system so far.

It will show that the endocannabinoid system is widely present in the retina, mostly in the through pathway where it can modulate neurotransmitter release and ion channel activity, although some evidence also indicates possible mechanisms via amacrine, horizontal, and Müller cells.

The presence of multiple endocannabinoid ligands, synthesizing and catabolizing enzymes, and receptors highlights various pharmacological targets for novel therapeutic application to retinal diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/26839718

Regulation of Stem Cells by the Endocannabinoid System

Posted on January 30, 2016 by David

“The endocannabinoids, endogenous lipid mediators of related chemical structure to the prototype exogenous cannabinoid Δ⁹-THC found in marijuana, have emerged as important mediators that regulate central and peripheral neural functions as well as immune responses.

Endogenous and exogenous cannabinoid ligands bind to cannabinoid receptors: the predominant central cannabinoid receptor type 1 (CB₁) and the peripheral cannabinoid receptor type 2 (CB₂). CB₁ and CB₂ are members of the G-protein coupled receptor family.

Cannabinoids were shown to modulate the immune system and to affect the migration of blood cells, such as T-cells, monocytes and myeloid leukemia cells, through CB receptors.

Recent data indicate the potential role of cannabinoid ligands and receptors in the regulation of hematopoiesis and hematopoietic stem cell (HSC) migration and trafficking.

These studies may lead to clinical applications of cannabinoid-based compounds as new HSC-mobilizer agents for therapeutic intervention in bone marrow failure.”

http://link.springer.com/chapter/10.1007/978-94-007-2993-3_30

Cannabinoid receptor 2 and its agonists mediate hematopoiesis and hematopoietic stem and progenitor cell mobilization.

Posted on January 30, 2016 by David

“Endocannabinoids are arachidonic acid derivatives and part of a novel bioactive lipid signaling system, along with their G-coupled cannabinoid receptors (CB₁ and CB₂) and the enzymes involved in their biosynthesis and degradation.

However, their roles in hematopoiesis and hematopoietic stem and progenitor cell (HSPC) functions are not well characterized. Here, we show that bone marrow stromal cells express endocannabinoids (anandamide and 2-arachidonylglycerol), whereas CB₂ receptors are expressed in human and murine HSPCs.

On ligand stimulation with CB₂ agonists, CB₂ receptors induced chemotaxis, migration, and enhanced colony formation of bone marrow cells, which were mediated via ERK, PI3-kinase, and Gαi-Rac1 pathways.

Taken together, these results demonstrate that the endocannabinoid system is involved in hematopoiesis and that CB₂/CB₂ agonist axis mediates repopulation of hematopoiesis and mobilization of HSPCs.

Thus, CB₂ agonists may be therapeutically applied in clinical conditions, such as bone marrow transplantation.”

http://www.ncbi.nlm.nih.gov/pubmed/21063029

Social defeat leads to changes in the endocannabinoid system; an overexpression of calreticulin and motor impairment in mice.

Posted on January 29, 2016 by David

“Social defeat leads to changes in the endocannabinoid system; an overexpression of calreticulin and motor impairment in mice… the aim of this study was to investigate the long-lasting effects of chronic psychosocial stress on motor coordination and motor learning, CB1 receptor expression, endogenous cannabinoid ligands and gene expression in the cerebellum. After chronic psychosocial stress, motor coordination and motor learning were impaired… The present study provides evidence that chronic stress activates calreticulin and might be one of the pathological mechanisms underlying the motor coordination and motor learning dysfunctions seen in social defeat mice.” http://www.ncbi.nlm.nih.gov/pubmed/26815100

Antidepressant-like effect of cannabidiol injection into the ventral medial prefrontal cortex – possible involvement of 5-HT1A and CB1 receptors.

Posted on January 25, 2016 by David

“Systemic administration of Cannabidiol (CBD), the main non-psychotomimetic constituent of Cannabis sativa, induces antidepressant-like effects.

The mechanism of action of CBD is thought to involve the activation of 5-HT1A receptors and the modulation of endocannabinoid levels with subsequent CB1 activation…

Administration of CBD into the vmPFC induces antidepressant-like effects possibly through indirect activation of CB1 and 5-HT1A receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/26801828

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

Rescue of Impaired mGluR5-Driven Endocannabinoid Signaling Restores Prefrontal Cortical Output to Inhibit Pain in Arthritic Rats.

Posted on January 23, 2016 by David

“Rescue of Impaired metabotropic glutamate receptor 5 (mGluR5)-Driven Endocannabinoid Signaling Restores Prefrontal Cortical Output to Inhibit Pain in Arthritic Rats…

Restoring endocannabinoid signaling allows mGluR5 activation to increase infralimbic output hence inhibit pain behaviors and mitigate pain-related cognitive deficits.”

http://www.ncbi.nlm.nih.gov/pubmed/26791214

http://www.thctotalhealthcare.com/category/arthritis/

Chronic alcohol exposure disrupts CB1 regulation of GABAergic transmission in the rat basolateral amygdala.

Posted on January 21, 2016 by David

“The basolateral nucleus of the amygdala (BLA) is critical to the pathophysiology of anxiety-driven alcohol drinking and relapse.

The endogenouscannabinoid/type 1 cannabinoid receptor (eCB/CB1 ) system curbs BLA-driven anxiety and stress responses via a retrograde negative feedback system that inhibits neurotransmitter release, and BLA CB1 activation reduces GABA release and drives anxiogenesis.

Additionally, decreased amygdala CB1 is observed in abstinent alcoholic patients and ethanol withdrawn rats.

Here, we investigated the potential disruption of eCB/CB1signaling on GABAergic transmission in BLA pyramidal neurons of rats exposed to 2-3 weeks intermittent ethanol.

In the naïve rat BLA, the CB1agonist WIN 55,212-2 (WIN) decreased GABA release, and this effect was prevented by the CB1 antagonist AM251. AM251 alone increased GABA release via a mechanism requiring postsynaptic calcium-dependent activity.

This retrograde tonic eCB/CB1 signaling was diminished in chronic ethanol exposed rats, suggesting a functional impairment of the eCB/CB1 system.

In contrast, acute ethanol increased GABAergic transmission similarly in naïve and chronic ethanol exposed rats, via both presynaptic and postsynaptic mechanisms.

Notably, CB1 activation impaired ethanol’s facilitation of GABAergic transmission across both groups, but the AM251-induced and ethanol-induced facilitation of GABA release was additive, suggesting independent presynaptic sites of action.

Collectively, the present findings highlight a critical CB1 influence on BLA GABAergic transmission that is dysregulated by chronic ethanol exposure and, thus, may contribute to the alcohol-dependent state.”

http://www.ncbi.nlm.nih.gov/pubmed/26786379

Ligands for cannabinoid receptors, promising anticancer agents.

Posted on January 15, 2016 by David

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“Cannabinoid compounds are unique to cannabis and provide some interesting biological properties.

These compounds along with endocannabinoids, a group of neuromodulator compounds in the body especially in brain, express their effects by activation of G-protein-coupled cannabinoid receptors, CB1 and CB2.

There are several physiological properties attributed to the endocannabinoids including pain relief, enhancement of appetite, blood pressure lowering during shock, embryonic development, and blocking of working memory.

On the other hand, activation of endocannabinoid system may be suppresses evolution and progression of several types of cancer.

According to the results of recent studies, CB receptors are over-expressed in cancer cell lines and application of multiple cannabinoid or cannabis-derived compounds reduce tumor size through decrease of cell proliferation or induction of cell cycle arrest and apoptosis along with desirable effect on decrease of tumor-evoked pain.

Therefore, modulation of endocannabinoid system by inhibition of fatty acid amide hydrolase (FAAH), the enzyme, which metabolized endocannabinoids, or application of multiple cannabinoid or cannabis-derived compounds, may be appropriate for the treatment of several cancer subtypes. This review focuses on how cannabinoid affect different types of cancers.”

http://www.ncbi.nlm.nih.gov/pubmed/26764235

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

An Introduction to the Endogenous Cannabinoid System.

Posted on December 25, 2015 by David

“The endocannabinoid system (ECS) is a widespread neuromodulatory system that plays important roles in central nervous system development, synaptic plasticity, and the response to endogenous and environmental insults.

The ECS comprises cannabinoid receptors, endogenouscannabinoids (endocannabinoids), and the enzymes responsible for the synthesis and degradation of the endocannabinoids.

The most abundant cannabinoid receptors are the CB1 cannabinoid receptors; however, CB2 cannabinoid receptors, transient receptor potential channels, and peroxisome proliferator activated receptors are also engaged by some cannabinoids.

Exogenous cannabinoids, such as tetrahydrocannabinol, produce their biological effects through their interactions with cannabinoid receptors.

The best-studied endogenous cannabinoids are 2-arachidonoyl glycerol and arachidonoyl ethanolamide (anandamide). Despite similarities in chemical structure, 2-arachidonoyl glycerol and anandamide are synthesized and degraded by distinct enzymatic pathways, which impart fundamentally different physiologic and pathophysiologic roles to these two endocannabinoids.

As a result of the pervasive social use of cannabis and the involvement of endocannabinoids in a multitude of biological processes, much has been learned about the physiologic and pathophysiologic roles of the ECS.

This review provides an introduction to the ECS with an emphasis on its role in synaptic plasticity and how the ECS is perturbed in schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/26698193