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Endocannabinoid

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https://www.readbyqxmd.com/read/28102227/singular-location-and-signaling-profile-of-adenosine-a2a-cannabinoid-cb1-receptor-heteromers-in-the-dorsal-striatum
#1
Estefanía Moreno, Anna Chiarlone, Mireia Medrano, Mar Puigdellívol, Lucka Bibic, Lesley A Howell, Eva Resel, Nagore Puente, María J Casarejos, Juan Perucho, Joaquín Botta, Nuria Suelves, Francisco Ciruela, Silvia Ginés, Ismael Galve-Roperh, Vicent Casadó, Pedro Grandes, Beat Lutz, Krisztina Monory, Enric I Canela, Carmen Lluís, Peter J McCormick, Manuel Guzmán
The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A2A receptor (A2AR) and cannabinoid CB1 receptor (CB1R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A2AR and CB1R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A2AR-CB1R heteromeric complexes...
January 19, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28100841/cannabinoids-a-new-weapon-against-cancer
#2
Małgorzata Pokrywka, Joanna Góralska, Bogdan Solnica
Cannabis has been cultivated by man since Neolithic times. It was used, among others for fiber and rope production, recreational purposes and as an excellent therapeutic agent. The isolation and characterization of the structure of one of the main active ingredients of cannabis - Δ9 - tetrahydrocannabinol as well the discovery of its cannabinoid binding receptors CB1 and CB2, has been a milestone in the study of the possibilities of the uses of Cannabis sativa and related products in modern medicine. Many scientific studies indicate the potential use of cannabinoids in the fight against cancer...
December 29, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28100744/compensatory-activation-of-cannabinoid-cb2-receptor-inhibition-of-gaba-release-in-the-rostral-ventromedial-medulla-in-inflammatory-pain
#3
Ming-Hua Li, Katherine L Suchland, Susan L Ingram
: The rostral ventromedial medulla (RVM) is a relay in the descending pain modulatory system and an important site of endocannabinoid modulation of pain. Endocannabinoids inhibit GABA release in the RVM, but it is not known whether this effect persists in chronic pain states. In the present studies, persistent inflammation induced by complete Freund's adjuvant (CFA) increased GABAergic miniature IPSCs (mIPSCs). Endocannabinoid activation of cannabinoid (CB1) receptors known to inhibit presynaptic GABA release was significantly reduced in the RVM of CFA-treated rats compared with naive rats...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28099629/the-role-of-the-cnr1-gene-in-schizophrenia-a-systematic-review-including-unpublished-data
#4
Eduardo S Gouvêa, Airton F Santos, Vanessa K Ota, Vinicius Mrad, Ary Gadelha, Rodrigo A Bressan, Quirino Cordeiro, Sintia I Belangero
Objective: Schizophrenia is a multifactorial disorder. It is known that a combination of extensive multiple common alleles may be involved in its etiology, each contributing with a small to moderate effect, and, possibly, some rare alleles with a much larger effect size. We aimed to perform a systematic review of association studies between schizophrenia (and its subphenotypes) and polymorphisms in the CNR1 gene, which encodes cannabinoid receptors classically implicated in schizophrenia pathophysiology, as well as to present unpublished results of an association study in a Brazilian population...
January 12, 2017: Revista Brasileira de Psiquiatria
https://www.readbyqxmd.com/read/28098721/the-endocannabinoid-system-and-its-role-in-eczematous-dermatoses
#5
Alexandra R Trusler, Ashley K Clark, Raja K Sivamani, Vivian Y Shi
The skin serves as the foremost barrier between the internal body and the external world, providing crucial protection against pathogens and chemical, mechanical, and ultraviolet damages. The skin is a central player in the intricate network of immune, neurologic, and endocrine systems. The endocannabinoid system (ECS) includes an extensive network of bioactive lipid mediators and their receptors, functions to modulate appetite, pain, mood, and memory, and has recently been implicated in skin homeostasis. Disruption of ECS homeostasis is implicated in the pathogenesis of several prevalent skin conditions...
January 2017: Dermatitis
https://www.readbyqxmd.com/read/28093016/acute-and-residual-effects-in-adolescent-rats-resulting-from-exposure-to-the-novel-synthetic-cannabinoids-ab-pinaca-and-ab-fubinaca
#6
Richard C Kevin, Katie E Wood, Jordyn Stuart, Andrew J Mitchell, Michael Moir, Samuel D Banister, Michael Kassiou, Iain S McGregor
Synthetic cannabinoids (SCs) have rapidly proliferated as recreational drugs, and may present a substantial health risk to vulnerable populations. However, information on possible effects of long-term use is sparse. This study compared acute and residual effects of the popular indazole carboxamide SC compounds AB-PINACA and AB-FUBINACA in adolescent rats with ∆(9)-tetrahydrocannabinol (THC) and control treatments. Albino Wistar rats were injected (i.p.) with AB-PINACA or AB-FUBINACA every second day (beginning post-natal day (PND) 31), first at a low dose (0...
January 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28092019/urb597-and-the-cannabinoid-win55-212-2-reduce-behavioral-and-neurochemical-deficits-induced-by-mptp-in-mice-possible-role-of-redox-modulation-and-nmda-receptors
#7
Angel Escamilla-Ramírez, Esperanza García, Guadalupe Palencia-Hernández, Ana Laura Colín-González, Sonia Galván-Arzate, Isaac Túnez, Julio Sotelo, Abel Santamaría
Several physiological events in the brain are regulated by the endocannabinoid system (ECS). While synthetic cannabinoid receptor (CBr) agonists such as WIN55,212-2 act directly on CBr, agents like URB597, a fatty acid amide hydrolase (FAAH) inhibitor, induce a more "physiological" activation of CBr by increasing the endogenous levels of the endocannabinoid anandamide (AEA). Herein, we compared the pre- and post-treatment efficacy of URB597 and WIN55,212-2 on different endpoints evaluated in the toxic model produced by the mitochondrial toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice...
January 14, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28088576/lid-domain-plasticity-and-lipid-flexibility-modulate-enzyme-specificity-in-human-monoacylglycerol-lipase
#8
Laura Riccardi, Jose M Arencibia, Luca Bono, Andrea Armirotti, Stefania Girotto, Marco De Vivo
Human monoacylglycerol lipase (MAGL) is a membrane-interacting enzyme that generates pro-inflammatory signaling molecules. For this reason, MAGL inhibition is a promising strategy to treat pain, cancer, and neuroinflammatory diseases. MAGL can hydrolyze monoacylglycerols bearing an acyl chain of different lengths and degrees of unsaturation, cleaving primarily the endocannabinoid 2-arachidonoylglycerol. Importantly, the enzymatic binding site of MAGL is confined by a 75-amino-acid-long, flexible cap domain, named 'lid domain', which is structurally similar to that found in several other lipases...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28087250/pharmacology-of-cannabinoids-in-the-treatment-of-epilepsy
#9
REVIEW
Tyler E Gaston, Daniel Friedman
The use of cannabis products in the treatment of epilepsy has long been of interest to researchers and clinicians alike; however, until recently very little published data were available to support its use. This article summarizes the available scientific data of pharmacology from human and animal studies on the major cannabinoids which have been of interest in the treatment of epilepsy, including ∆9-tetrahydrocannabinol (∆9-THC), cannabidiol (CBD), ∆9-tetrahydrocannabivarin (∆9-THCV), cannabidivarin (CBDV), and ∆9-tetrahydrocannabinolic acid (Δ9-THCA)...
January 10, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28086912/wwl70-attenuates-pge2-production-derived-from-2-arachidonoylglycerol-in-microglia-by-abhd6-independent-mechanism
#10
Mikiei Tanaka, Sean Moran, Jie Wen, Kwame Affram, Tinghua Chen, Aviva J Symes, Yumin Zhang
BACKGROUND: α/β-Hydrolase domain 6 (ABHD6) is one of the major enzymes for endocannabinoid 2-arachidonoylglycerol (2-AG) hydrolysis in microglia cells. Our recent studies have shown that a selective ABHD6 inhibitor WWL70 has anti-inflammatory and neuroprotective effects in animal models of traumatic brain injury and multiple sclerosis. However, the role of ABHD6 in the neuroinflammatory response and the mechanisms by which WWL70 suppresses inflammation has not yet been elucidated in reactive microglia...
January 10, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28079617/manipulation-of-the-endocannabinoid-system-in-colitis-a-comprehensive-review
#11
Kristina L Leinwand, Mark E Gerich, Edward J Hoffenberg, Colm B Collins
BACKGROUND: Inflammatory bowel disease (IBD) is a lifelong disease of the gastrointestinal tract whose annual incidence and prevalence is on the rise. Current immunosuppressive therapies available for treatment of IBD offer limited benefits and lose effectiveness, exposing a significant need for the development of novel therapies. In the clinical setting, cannabis has been shown to provide patients with IBD symptomatic relief, although the underlying mechanisms of their anti-inflammatory effects remain unclear...
January 10, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28078867/plasma-endocannabinoid-behaviour-in-total-knee-and-hip-arthroplasty
#12
R Ottria, L Cappelletti, A Ravelli, M Mariotti, F Gigli, S Romagnoli, P Ciuffreda, G Banfi, L Drago
Endocannabinoids are a class of lipid mediators involved in a wide range of physiological pathways including pain perception, and immunological defences. In particular, the involvement of endocannabinoids in bone metabolism and bone resorption has recently been studied. Moreover, one study on total knee arthroplasty describes the probable role of endocannabinoids in pain perception after surgery. The aim of the present study was to evaluate variations of endocannabinoid concentrations in patients undergoing total hip or total knee arthroplasty before and after surgery...
October 2016: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28069688/up-regulation-of-cb2-receptors-in-reactive-astrocytes-in-canine-degenerative-myelopathy-a-disease-model-of-amyotrophic-lateral-sclerosis
#13
María Fernández-Trapero, Francisco Espejo-Porras, Carmen Rodríguez-Cueto, Joan R Coates, Carmen Pérez-Díaz, Eva de Lago, Javier Fernández-Ruiz
Targeting the CB2 receptor afforded neuroprotection in SOD1(G93A) mutant mice, a model of amyotrophic lateral sclerosis (ALS). The neuroprotective effects of CB2 receptors were facilitated by their up-regulation in the spinal cord in SOD1(G93A) mutant mice. Herein, we have investigated whether a similar CB2 receptor up-regulation, as well as parallel changes in other endocannabinoid elements, are evident in the spinal cord of dogs with degenerative myelopathy (DM), caused from mutations in the superoxide dismutase 1 gene (SOD1)...
January 9, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28065722/peripheral-endocannabinoid-signaling-controls-hyperphagia-in-western-diet-induced-obesity
#14
Donovan A Argueta, Nicholas V DiPatrizio
The endocannabinoid system in the brain and periphery plays a major role in controlling food intake and energy balance. We reported that tasting dietary fats was met with increased levels of the endocannabinoids, 2-arachidonoyl-sn-glycerol (2-AG) and anandamide, in the rat upper small intestine, and pharmacological inhibition of this local signaling event dose-dependently blocked sham feeding of fats. We now investigated the contribution of peripheral endocannabinoid signaling in hyperphagia associated with chronic consumption of a western-style diet in mice ([WD] i...
January 5, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28063756/-synthetic-cannabinoids-a-new-addiction-matrix
#15
Amandine Scocard, Amine Benyamina, Sarah Coscas, Laurent Karila
Synthetic cannabinoids (SC) belong to the emergent market of new psychoactive substances, sold on the Internet or specialized shops. Since the 1970s, more than 160 new SC have invaded the drug market. These substances imitate the psychoactive effects of cannabis. Underestimated for too long, SC's market growth and consequences are no longer to be ignored, first of all in terms of public health. SC were first synthesized during researches on the endocannabinoid system. Though they are agonists of the cannabinoid receptors 1 and 2, as Δ9-tetrahydrocannabinol in cannabis, they can also have a really high affinity with these receptors, rising up their potency...
January 4, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/28062195/development-of-new-inhibitors-for-n-acylethanolamine-hydrolyzing-acid-amidase-as-promising-tool-against-bladder-cancer
#16
Riccardo Vago, Arianna Bettiga, Andrea Salonia, Pierangela Ciuffreda, Roberta Ottria
The endocannabinoid system is a signaling system involved in a wide range of biological effects. Literature strongly suggests the endocannabinoid system role in the pathogenesis of cancer and that its pharmacological activation produces therapeutic benefits. Last research promotes the endocannabinoid system modulation by inhibition of endocannabinoids hydrolytic enzymes instead of direct activation of endocannabinoid receptors to avoid detrimental effects on cognition and motor control. Here we report the identification of N-acylethanolamine-hydrolyzing acid amidase (NAAA) inhibitors able to reduce cell proliferation and migration and cause cell death on different bladder cancer cell lines...
December 27, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28061971/the-endocannabinoid-system-and-anxiety
#17
S F Lisboa, F V Gomes, A L B Terzian, D C Aguiar, F A Moreira, L B M Resstel, F S Guimarães
The medical properties of Cannabis sativa is known for centuries. Since the discovery and characterization of the endogenous cannabinoid system, several studies have evaluated how cannabinoid compounds and, particularly, how the modulation of the endocannabinoid (eCB) system influences a wide range of functions, from metabolic to mental disorders. Cannabinoids and eCB system often exert opposite effects on several functions, such as anxiety. Although the mechanisms are not completely understood, evidence points to different factors influencing those effects...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28061690/organophosphorus-xenobiotic-toxicology
#18
John E Casida
Originally, organophosphorus (OP) toxicology consisted of acetylcholinesterase inhibition by insecticides and chemical threat agents acting as phosphorylating agents for serine in the catalytic triad, but this is no longer the case. Other serine hydrolases can be secondary OP targets, depending on the OP structure, and include neuropathy target esterase, lipases, and endocannabinoid hydrolases. The major OP herbicides are glyphosate and glufosinate, which act in plants but not animals to block aromatic amino acid and glutamine biosynthesis, respectively, with safety for crops conferred by their expression of herbicide-tolerant targets and detoxifying enzymes from bacteria...
January 6, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28060830/association-between-use-of-cannabis-in-adolescence-and-weight-change-into-midlife
#19
Lexie Zhiyan Jin, Anna Rangan, Jesper Mehlsen, Lars Bo Andersen, Sofus C Larsen, Berit L Heitmann
Cannabis use has been found to stimulate appetite and potentially promote weight gain via activation of the endocannabinoid system. Despite the fact that the onset of cannabis use is typically during adolescence, the association between adolescence cannabis use and long-term change in body weight is generally unknown. This study aims to examine the association between adolescence cannabis use and weight change to midlife, while accounting for the use of other substances. The study applied 20 to 22 years of follow-up data on 712 Danish adolescents aged between 15 and 19 years at baseline...
2017: PloS One
https://www.readbyqxmd.com/read/28046144/endocannabinoids-concentrations-in-plasma-associated-with-feed-efficiency-and-carcass-composition-of-beef-steers
#20
V M Artegoitia, A P Foote, R M Lewis, D A King, S D Shackelford, T L Wheeler, H C Freetly
Endocannabinoids, including anandamide (AEA) and 2-arachidonoylglycerol (2-AG), are a class of endogenous lipid mediators that activate cannabinoids receptors and may be involved in the control of feed intake and energy metabolism. The objective of this study was to quantify AEA and 2-AG in plasma and identify possible associations with production traits and carcass composition in finishing beef steers. Individual DMI and BW gain were measured on 140 Angus-sired steers for 105 d on a finishing ration. Blood samples were collected on d 84 of the experiment, which was 40 d before slaughter...
December 2016: Journal of Animal Science
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