Category Archives: Endocannabinoid System

WIN 55,212-2, Agonist of Cannabinoid Receptors, Prevents Amyloid β1-42 Effects on Astrocytes in Primary Culture.

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“Alzheimer´s disease (AD), a neurodegenerative illness involving synaptic dysfunction with extracellular accumulation of Aβ1-42 toxic peptide, glial activation, inflammatory response and oxidative stress, can lead to neuronal death.

Endogenous cannabinoid system is implicated in physiological and physiopathological events in central nervous system (CNS), and changes in this system are related to many human diseases, including AD…

In conclusion cannabinoid WIN 55,212-2 increases cell viability and anti-inflammatory response in cultured astrocytes. Moreover, WIN 55,212-2 increases expression of anti-oxidant Cu/Zn SOD and is able to prevent inflammation induced by Aβ1-42 in cultured astrocytes.

Further studies would be needed to assess the possible beneficial effects of cannabinoids in Alzheimer’s disease patients.”

http://www.ncbi.nlm.nih.gov/pubmed/25874692

http://www.thctotalhealthcare.com/category/alzheimers-disease-ad/

A role for GPR55 in human placental venous endothelial cells.

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“Endocannabinoids and their G protein-coupled receptors have been suggested to play a key role in human pregnancy, by regulating important aspects such as implantation, decidualization, placentation and labor.

G protein-coupled receptor 55 (GPR55) was previously postulated to be another cannabinoid receptor, since specific cannabinoids were shown to act independently of the classical cannabinoid receptors CB1 or CB2.

Current knowledge about GPR55 expression and function in human placenta is very limited and motivated us to evaluate human placental GPR55 expression in relation to other human peripheral tissues and to analyze spatiotemporal GPR55 expression in human placenta.

Gene expression analysis revealed low GPR55 levels in human placenta, when compared to spleen and lung, the organs showing highest GPR55 expression.

Moreover, expression analysis showed 5.8 fold increased placental GPR55 expression at term compared to first trimester. Immunohistochemistry located GPR55 solely at the fetal endothelium of first trimester and term placentas. qPCR and immunocytochemistry consistently confirmed GPR55 expression in isolated primary placental arterial and venous endothelial cells. Incubation with L-α-lysophosphatidylinositol (LPI), the specific and functional ligand for GPR55, at a concentration of 1 µM, significantly enhanced migration of venous, but not arterial endothelial cells.

LPI-enhanced migration was inhibited by the GPR55 antagonist O-1918, suggesting a role of the LPI-GPR55 axis in placental venous endothelium function.”

Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context.

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“Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis.

The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study…

Main results indicated that FAAH inhibitor URB597 decreased neural proliferation, glia and apoptosis in a brain region-dependent manner, which were coupled to local changes in Faah and/or Cnr1 expression and a negative energy context.”

http://www.ncbi.nlm.nih.gov/pubmed/25870539

The effect of FAAH, MAGL, and Dual FAAH/MAGL inhibition on inflammatory and colorectal distension-induced visceral pain models in Rodents.

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“Recent studies showed that the pharmacological inhibition of endocannabinoid degrading enzymes such as fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) elicit promising analgesic effects in a variety of nociceptive models without serious side effects…

The selective FAAH inhibitor and dual FAAH/MAGL inhibitors were effective in both inflammatory and mechanically evoked visceral pain, while the MAGL inhibitor elicited an analgesic effect in inflammatory, but not in distension-induced, visceral pain.”

http://www.ncbi.nlm.nih.gov/pubmed/25869205

Negative Regulation of Leptin-induced ROS Formation by CB1 Receptor Activation in Hypothalamic Neurons.

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“The adipocyte-derived, anorectic hormone, leptin, was recently shown to owe part of its regulatory effects on appetite-regulating hypothalamic neuropeptides to the elevation of ROS levels in arcuate nucleus (ARC) neurons.

Leptin is also known to exert a negative regulation on hypothalamic endocannabinoid levels and hence on cannabinoid CB1 receptor activity.

Here we investigated the possibility of a negative regulation by CB1 receptor of leptin-mediated ROS formation in the ARC…

We conclude that CB1 activation reverses leptin-induced ROS formation, and hence possibly some of the ROS-mediated effects of the hormone, by preventing PPAR-γ inhibition by leptin, with subsequent increase of catalase activity.

This mechanism might underlie in part CB1 orexigenic actions under physiopathological conditions accompanied by elevated hypothalamic endocannabinoid levels.”

Minireview: From the Bench, Toward the Clinic: Therapeutic Opportunities for Cannabinoid Receptor Modulation.

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The effects of cannabinoids have been known for centuries and over the past several decades two G-protein coupled receptors, CB1 and CB2, have been identified that are responsible for their activity.

Endogenous lipid-derived cannabinergic agents have been found, biosynthetic and catabolic machinery characterized, and synthetic agents have been designed to modulate these receptors.

Selective agents including agonists, antagonists, inverse agonists and novel allosteric modulators targeting either CB1 or CB2 have been developed to inhibit or augment their basal tone.

As a result, the role these receptors play in human physiology and their potential therapeutic applications in disease states are being elucidated.

The CB1 receptor while ubiquitous is densely expressed in the brain and CB2 is largely found on cells of immune origin.

This minireview highlights the role of CB1 in excitotoxic assaults in the brain and its potential to limit addiction liability.

In addition, it will examine the relationship between receptor activity and stimulation of insulin release from pancreatic β-cells, insulin resistance and feeding behavior leading toward obesity.

The role of CB2 in the neuropathology of amyotrophic lateral sclerosis and in the central manifestations of chronic HIV infection potentially converges at inflammatory cell activation thereby providing an opportunity for intervention.

Lastly, CB2 modulation is discussed in the context of an experimental model of post-menopausal osteoporosis.

Achieving exquisite receptor selectivity and elucidating the mechanisms underlying receptor inhibition and activation will be essential for the development of the next generation of cannabinergic-based therapeutic agents.”

CB1 receptors modulate affective behaviour induced by neuropathic pain.

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“Patients suffering from chronic pain are often also diagnosed with a psychiatric condition, in particular generalized anxiety and major depression. The underlying pathomechanisms contributing to this comorbidity, however, are not entirely clear.

In this manuscript we have focussed on the potential role of the cannabinoid receptor CB1, because it is known to modulate neuronal circuits contributing to chronic pain states and affective behaviours.

For this purpose we analysed the consequences of a partial sciatic nerve ligation on anxiety- and depression related behaviours in mice lacking CB1 receptors.

Our results show that the development of mechanical hypersensitivity was similar in CB1 deficient mice and wild type controls. However, CB1 knockouts showed much more pronounced behavioural manifestations of anxiety-related behaviors in the light-dark and zero-maze tests, sucrose anhedonia, and disturbed home-cage activity.

These results indicate that the endocannabinoid system affects chronic pain-induced mood changes through CB1 receptors.”

Simultaneous determination of endocannabinoids in murine plasma and brain substructures by surrogate-based LC-MS/MS: Application in tumor-bearing mice.

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“The endocannabinoids (eCBs), N-arachidonoylethanolamine (anandamide, AEA) and 2-ararchidonylglycerol (2-AG) have been identified as main endogenous ligands for cannabinoid receptors.

Developing a sensitive and robust method to determine AEA and 2-AG has been shown to be essential to understand their effects in stress regulation and the pathogenesis of affective disorders.

Detection was performed in multiple reaction monitoring (MRM) mode with an electrospray ionization source operated in positive ion mode. The method was applied to assess plasma and brain eCBs in tumor-bearing mice.”

http://www.ncbi.nlm.nih.gov/pubmed/25863017

Role of the endogenous cannabinoid system in nicotine addiction: novel insights.

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“Several lines of evidence have shown that the endogenous cannabinoids are implicated in several neuropsychiatric diseases. Notably, preclinical and human clinical studies have shown a pivotal role of the cannabinoid system in nicotine addiction.

The CB1 receptor inverse agonist/antagonist rimonabant (also known as SR141716) was effective to decrease nicotine-taking and nicotine-seeking in rodents, as well as the elevation of dopamine induced by nicotine in brain reward area. Rimonabant has been shown to improve the ability of smokers to quit smoking in randomized clinical trials. However, rimonabant was removed from the market due to increased risk of psychiatric side-effects observed in humans.

Recently, other components of the endogenous cannabinoid system have been explored. Here, we present the recent advances on the understanding of the role of the different components of the cannabinoid system on nicotine’s effects.

Those recent findings suggest possible alternative ways of modulating the cannabinoid system that could have implication for nicotine dependence treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/25859226

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

Cannabinoids receptor type 2, CB2, expression correlates with human colon cancer progression and predicts patient survival.

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“Many studies have demonstrated that the endocannabinoid system (ECS) is altered in different tumor types, including colon cancer.

However, little is known about the role of the ECS in tumor progression.

Here we report the correlation between CB 2 expression and pathological data in a series of 175 colorectal cancer patients, as well as the response of the HT29 colon cancer-derived cell line upon CB 2 activation…

These results raise the question whether the activation of CB 2 should be considered as anti-tumoral therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/25859556

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