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  • 2-AG, Anandamide, cannabidiol, cannabinoid receptor 1, cannabinoid receptor-2, Cannabis, CB(2), CB1, CBC, CBD, CBG, endocannabinoid system, G-coupled protein receptor, GPR55, Ht1a, PPARS a, tetrahydrocannabinol, THC, trpv1
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The Endocannabinoid System of Animals

Our understanding of the Endocannabinoid System of animals, and its ubiquitous presence in nearly all members of Animalia, has opened the door to novel approaches targeting pain management, cancer therapeutics, modulation of neurologic disorders, stress reduction, anxiety management, and inflammatory diseases. Both endogenous and exogenous endocannabinoid-related molecules are able to function as direct ligands or, otherwise, influence the EndoCannabinoid System (ECS). This review article introduces the reader to the ECS in animals, and documents its potential as a source for emerging therapeutics.
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Cannabinoids and bone: endocannabinoids modulate human osteoclast function in vitro

BACKGROUND AND PURPOSE Both CB1 and CB2 cannabinoid receptors have been shown to play a role in bone metabolism. Crucially, previous studies have focussed on the effects of cannabinoid ligands in murine bone cells. This study aimed to investigate the effects of cannabinoids on human bone cells in vitro. EXPERIMENTAL APPROACH Quantitative RT-PCR was used to determine expression of cannabinoid receptors and liquid chromatography-electrospray ionization tandem mass spectrometry was used to determine the presence of endocannabinoids in human bone cells. The effect of cannabinoids on human osteoclast formation, polarization and resorption was determined by assessing the number of cells expressing avb3 or with F-actin...
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Endocannabinoid Binding to the Cannabinoid Receptors: What Is Known and What Remains Unknown

The cannabinoid CB1 and CB2 receptors are Class A G protein-coupled receptors (GPCRs). While many Class A GPCRs have endogenous ligands that are hydrophilic cations (e.g., the serotonin and dopamine receptors), the cannabinoid receptors have neutral, highly lipophilic ligands derived from the fatty acid, arachidonic acid. The most well-studied of these are Narachidonoylethanolamine (anandamide, AEA) and sn-2-arachidonoylglycerol (2-AG). This review focuses on the experimental and computational studies that have been used to probe the nature of endocannabinoid interaction with the cannabinoid receptors. These studies include mutation, SAR and NMR studies, as well as, QSAR, docking and molecular dynamics simulations. Gaps in our knowledge are...
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Estrogen Receptor Beta and 2-arachidonoylglycerol Mediate the Suppressive Effects of Estradiol on Frequency of Postsynaptic Currents in Gonadotropin-Releasing Hormone Neurons of Metestrous Mice: An Acute Slice Electrophysiological Study

Gonadotropin-releasing hormone (GnRH) neurons are controlled by 17β-estradiol (E2) contributing to the steroid feedback regulation of the reproductive axis. In rodents, E2 exerts a negative feedback effect upon GnRH neurons throughout the estrus-diestrus phase of the ovarian cycle. The present study was undertaken to reveal the role of estrogen receptor subtypes in the mediation of the E2 signal and elucidate the downstream molecular machinery of suppression. The effect of E2 administration at low physiological concentration (10 pM) on GnRH neurons in acute brain slices obtained from metestrous GnRH-green fluorescent protein (GFP) mice was studied under paradigms of blocking or activating estrogen receptor subtypes and...
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Mitochondria: a possible nexus for the regulation of energy homeostasis by the endocannabinoid system?

Mitochondria: a possible nexus for the regulation of energy homeostasis by the endocannabinoid system?. Am J Physiol Endocrinol Metab 307: E1–E13, 2014. First published May 6, 2014; doi:10.1152/ajpendo.00100.2014.—The endocannabinoid system (ECS) regulates numerous cellular and physiological processes through the activation of receptors targeted by endogenously produced ligands called endocannabinoids. Importantly, this signaling system is known to play an important role in modulating energy balance and glucose homeostasis. For example, current evidence indicates that the ECS becomes overactive during obesity whereby its central and peripheral stimulation drives metabolic processes that mimic the metabolic syndrome. Herein, we examine the role of the ECS in modulating the...
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The neuroprotective role of endocannabinoids against chemical-induced injury and other adverse effects

Considerable progress has been made, recently, in understanding the role of the endocannabinoid system in regard to neuroprotection. Endogenous cannabinoids have received increasing attention as potential protective agents in several cases of neuronal injury. The endocannabinoid system is comprised of cannabinoid receptors (CB1 and CB2), their endogenous ligands (endocannabinoids) and proteins responsible for their metabolism. Endocannabinoids serve as retrograde signalling messengers in GABAergic and glutamatergic synapses, as well as modulators of post-synaptic transmission, interacting with other neurotransmitters, including norepinephrine and dopamine. Furthermore, endocannabinoids modulate neuronal, glial and endothelial cell function and exert neuromodulatory, anti-excitotoxic, anti-inflammatory and vasodilatory effects. Physiological stimuli and pathological conditions lead...
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The potential relevance of the endocannabinoid, 2- arachidonoylglycerol, in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma is an aggressive, genetically heterogenerous disease and the most common type of non-Hodgkin lymphoma among adults. To gain further insights into the etiology of DLBCL and to discover potential diseaserelated factors, we performed a serum lipid analysis on a subset of individuals from a population-based NHL case-control study. An untargeted mass-spectrometry-based metabolomics platform was used to analyze serum samples from 100 DLBCL patients and 100 healthy matched controls. Significantly elevated levels of the endocannabinoid, 2-arachidonoylglycerol (2-AG), were detected in the serum of DLBCL patients (121%, P<0.05). In the male controls, elevated 2-AG levels were observed in those who were overweight...
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The Role of Endocannabinoid Signaling in the Molecular Mechanisms of Neurodegeneration in Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common form of progressive neurodegenerative disease characterized by cognitive impairment and mental disorders. The actual cause and cascade of events in the progression of this pathology is not fully determined. AD is multifaceted in nature and is linked to different multiple mechanisms in the brain. This aspect is related to the lack of efficacious therapies that could slow down or hinder the disease onset/progression. The ideal treatment for AD should be able to modulate the disease through multiple mechanisms rather than targeting a single dysregulated pathway. Recently, the endocannabinoid system emerged as novel potential therapeutic target to treat...
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