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https://www.readbyqxmd.com/read/29773016/is-cannabidiol-a-promising-substance-for-new-drug-development-a-review-of-its-potential-therapeutic-applications
#1
Nida Noreen, Faqir Muhammad, Bushra Akhtar, Farooq Azam, Muhammad Irfan Anwar
The pharmacological importance of cannabidiol (CBD) has been in study for several years. CBD is the major nonpsychoactive constituent of plant Cannabis sativa and its administration is associated with reduced side effects. Currently, CBD is undergoing a lot of research which suggests that it has no addictive effects, good safety profile and has exhibited powerful therapeutic potential in several vital areas. It has wide spectrum of action because it acts through endocannabinoid receptors; CB1 and CB2 and it also acts on other receptors, such as GPR18, GPR55, GPR 119, 5HT1A, and TRPV2...
2018: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/29745439/cannabinoids-and-gastrointestinal-motility-pharmacology-clinical-effects-and-potential-therapeutics-in-humans
#2
REVIEW
M Camilleri
BACKGROUND: Cannabinoid agents and cannabis are frequently used for relief of diverse gastrointestinal symptoms. PURPOSE: The objective of this article is to increase the awareness of gastroenterologists to the effects of cannabinoids on gastrointestinal motility, as gastroenterologists are likely to encounter patients who are taking cannabinoids, or those with dysmotility that may be associated with cannabinoid mechanisms. The non-selective cannabinoid agonist, dronabinol, retards gastric emptying and inhibits colonic tone and phasic pressure activity...
May 10, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29694340/possible-role-of-hippocampal-gpr55-in-spatial-learning-and-memory-in-rats
#3
Bruno A Marichal-Cancino, Alfonso Fajardo-Valdez, Alejandra E Ruiz-Contreras, Mónica Méndez-Díaz, Oscar Prospéro-García
Endocannabinoids (eCBs) are involved in the hippocampal mechanisms of spatial learning and memory in rats. Although eCBs exert many of their actions on spatial learning and memory via CB1 receptors, the putative cannabinoid receptor GPR55 (expressed in the hippocampus, cortex, forebrain, cerebellum and striatum) seems to be also involved. To investigate the potential role of GPR55 in spatial learning and memory, Wistar rats received bilateral infusions of lysophosphatidylinositol (LPI, GPR55‑agonist) into the hippocampus 5‑minutes before training‑phase in the Barnes‑maze (BM)...
2018: Acta Neurobiologiae Experimentalis
https://www.readbyqxmd.com/read/29588059/lysophosphatidylinositols-from-cell-membrane-constituents-to-gpr55-ligands
#4
REVIEW
Mireille Alhouayek, Julien Masquelier, Giulio G Muccioli
Lysophosphatidylinositols (LPIs) are membrane constituents that alter the properties of said membranes. However, recent data showing that the once orphan receptor, GPR55, can act as a receptor for LPIs has sparked a renewed interest in LPIs as bioactive lipids. As evidence supporting the importance of LPIs and/or GPR55 is continuously accumulating and because LPI levels are altered in a number of pathologies such as obesity and cancer, the coming years should bring new, exciting discoveries to this field. In this review, we discuss the recent work on LPIs and on their molecular target, the GPR55 receptor...
March 24, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/29435814/alterations-in-gene-and-protein-expression-of-cannabinoid-cb-2-and-gpr55-receptors-in-the-dorsolateral-prefrontal-cortex-of-suicide-victims
#5
María S García-Gutiérrez, Francisco Navarrete, Gemma Navarro, Irene Reyes-Resina, Rafael Franco, Jose Luis Lanciego, Salvador Giner, Jorge Manzanares
Recent studies point to the cannabinoid CB2 receptors (CB2 r) and the non-cannabinoid receptor GPR55 as potential key targets involved in the response to stress, anxiety, and depression. Considering the close relationship between neuropsychiatric disorders and suicide, the purpose of this study was to evaluate the potential alterations of CB2 r and GPR55 in suicide victims. We analyzed gene and protein expression of both receptors by real-time PCR and western blot, respectively, in the dorsolateral prefrontal cortex (DLPFC) of 18 suicide victims with no clinical psychiatric history or treatment with anxiolytics or antidepressants, and 15 corresponding controls...
February 12, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29304078/the-endocannabinoid-gene-faah2a-modulates-stress-associated-behavior-in-zebrafish
#6
Randall G Krug, Han B Lee, Louis Y El Khoury, Ashley N Sigafoos, Morgan O Petersen, Karl J Clark
The ability to orchestrate appropriate physiological and behavioral responses to stress is important for survival, and is often dysfunctional in neuropsychiatric disorders that account for leading causes of global disability burden. Numerous studies have shown that the endocannabinoid neurotransmitter system is able to regulate stress responses and could serve as a therapeutic target for the management of these disorders. We used quantitative reverse transcriptase-polymerase chain reactions to show that genes encoding enzymes that synthesize (abhd4, gde1, napepld), enzymes that degrade (faah, faah2a, faah2b), and receptors that bind (cnr1, cnr2, gpr55-like) endocannabinoids are expressed in zebrafish (Danio rerio)...
2018: PloS One
https://www.readbyqxmd.com/read/29225068/lysophosphatidylcholine-and-its-phosphorothioate-analogues-potentiate-insulin-secretion-via-gpr40-ffar1-gpr55-and-gpr119-receptors-in-a-different-manner
#7
Anna Drzazga, Hjalti Kristinsson, Maciej Sałaga, Hubert Zatorski, Maria Koziołkiewicz, Edyta Gendaszewska-Darmach, Peter Bergsten
Lysophosphatidylcholine (LPC) is an endogenous ligand for GPR119 receptor, mediating glucose-stimulated insulin secretion (GSIS). We demonstrate that LPC facilitates GSIS in MIN6 pancreatic β-cell line and murine islets of Langerhans by recognizing not only GPR119 but also GPR40 (free fatty acid receptor 1) and GPR55 activated by lysophosphatidylinositol. Natural LPCs are unstable when administered in vivo limiting their therapeutic value and therefore, we present phosphorothioate LPC analogues with increased stability...
December 8, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29222090/gpr55-regulates-intraepithelial-lymphocyte-migration-dynamics-and-susceptibility-to-intestinal-damage
#8
Hayakazu Sumida, Erick Lu, Hsin Chen, Qiyun Yang, Ken Mackie, Jason G Cyster
Intraepithelial lymphocytes (IELs) of the small intestine are intimately associated with the epithelial cells. Yet, the factors controlling their migration and interaction dynamics are poorly understood. We demonstrate that GPR55, a receptor that mediates migration inhibition in response to lysophosphatidylinositol (LPI), negatively regulates T cell receptor γδ (TCRγδ) IEL accumulation in the small intestine. Intravital imaging studies show that GPR55-deficient IELs migrate faster and interact more extensively with epithelial cells...
December 8, 2017: Science Immunology
https://www.readbyqxmd.com/read/29205751/lh-21-and-abnormal-cannabidiol-improve-%C3%AE-cell-function-in-isolated-human-and-mouse-islets-through-gpr55-dependent-and-independent-signalling
#9
Inmaculada Ruz-Maldonado, Attilio Pingitore, Bo Liu, Patricio Atanes, Guo Cai Huang, David Baker, Francisco José Alonso, Francisco Javier Bermúdez-Silva, Shanta J Persaud
AIMS: To examine the effects of Abn-CBD (GPR55 agonist) and LH-21 (CB1 antagonist) on human and mouse islet function, and to determine signalling via GPR55 using islets from GPR55-/- mice. MATERIALS AND METHODS: Islets isolated from human organ donors and mice were incubated in the absence or presence of Abn-CBD or LH-21, and insulin secretion, [Ca2+ ]i, cAMP, apoptosis, β-cell proliferation and CREB and AKT phosphorylation were examined using standard techniques...
April 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29188802/the-lpi-gpr55-axis-enhances-human-breast-cancer-cell-migration-via-hbxip-and-p-mlc-signaling
#10
Xiao-Lei Zhou, Xin Guo, Yu-Pin Song, Chong-Yue Zhu, Wei Zou
The G protein-coupled receptor 55 (GPR55) is expressed in multiple tissues, and has been implicated in cancer pathogenesis, but little is known about its role in the migratory behavior of cancer cells, particularly breast cancer cells. In this study we first showed that GPR55 expression levels in 38 metastatic lymph nodes of breast cancer patients were profoundly elevated, and were positively associated in human breast cancer cells with their migratory ability. Moreover, the plasma levels of GPR55 endogenous agonist L-a-lysophosphatidylinositol (LPI) were significantly increased in breast cancer patients compared with healthy individuals...
March 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29155298/mechanisms-of-l-alpha-lysophosphatidylinositol-induced-relaxation-in-human-pulmonary-arteries
#11
Olga Karpińska, Marta Baranowska-Kuczko, Barbara Malinowska, Monika Kloza, Magdalena Kusaczuk, Agnieszka Gęgotek, Paweł Golec, Irena Kasacka, Hanna Kozłowska
AIMS: l-Alpha-lysophosphatidylinositol (LPI) is an endogenous agonist of G protein-coupled receptor 55 (GPR55) which relaxes mesenteric arteries on activation. The aim of the present study was to determine the influence and underlying mechanisms of LPI-induced relaxation in human pulmonary arteries (hPAs). MAIN METHODS: Functional studies were performed in isolated hPAs using organ bath technique. The expression of GPR55 in hPAs and bronchioles was determined by real-time qPCR, Western blot analysis, and immunohistochemistry...
January 1, 2018: Life Sciences
https://www.readbyqxmd.com/read/29098189/an-update-on-non-cb-1-non-cb-2-cannabinoid-related-g-protein-coupled-receptors
#12
REVIEW
Paula Morales, Patricia H Reggio
The endocannabinoid system (ECS) has been shown to be of great importance in the regulation of numerous physiological and pathological processes. To date, two Class A G-protein-coupled receptors (GPCRs) have been discovered and validated as the main therapeutic targets of this system: the cannabinoid receptor type 1 (CB1 ), which is the most abundant neuromodulatory receptor in the brain, and the cannabinoid receptor type 2 (CB2 ), predominantly found in the immune system among other organs and tissues. Endogenous cannabinoid receptor ligands (endocannabinoids) and the enzymes involved in their synthesis, cell uptake, and degradation have also been identified as part of the ECS...
2017: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/29098187/review-the-role-of-cannabinoids-on-esophageal-function-what-we-know-thus-far
#13
REVIEW
Jonathan Gotfried, Rahul Kataria, Ron Schey
The endocannabinoid system (ECS) primarily consists of cannabinoid receptors (CBRs), endogenous ligands, and enzymes for endocannabinoid biosynthesis and inactivation. Although the presence of CBRs, both CB1 and CB2 , as well as a third receptor (G-protein receptor 55 [GPR55]), has been established in the gastrointestinal (GI) tract, few studies have focused on the role of cannabinoids on esophageal function. To date, studies have shown their effect on GI motility, inflammation and immunity, intestinal and gastric acid secretion, nociception and emesis pathways, and appetite control...
2017: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/29082314/anti-inflammatory-activity-in-colon-models-is-derived-from-%C3%AE-9-tetrahydrocannabinolic-acid-that-interacts-with-additional-compounds-in-cannabis-extracts
#14
Rameshprabu Nallathambi, Moran Mazuz, Aurel Ion, Gopinath Selvaraj, Smadar Weininger, Marcelo Fridlender, Ahmad Nasser, Oded Sagee, Puja Kumari, Diana Nemichenizer, Maayan Mendelovitz, Nave Firstein, Orly Hanin, Fred Konikoff, Yoram Kapulnik, Timna Naftali, Hinanit Koltai
Introduction: Inflammatory bowel diseases (IBDs) include Crohn's disease, and ulcerative colitis. Cannabis sativa preparations have beneficial effects for IBD patients. However, C. sativa extracts contain hundreds of compounds. Although there is much knowledge of the activity of different cannabinoids and their receptor agonists or antagonists, the cytotoxic and anti-inflammatory activity of whole C. sativa extracts has never been characterized in detail with in vitro and ex vivo colon models. Material and Methods: The anti-inflammatory activity of C...
2017: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/28973916/cannabidiol-attenuates-seizures-and-social-deficits-in-a-mouse-model-of-dravet-syndrome
#15
Joshua S Kaplan, Nephi Stella, William A Catterall, Ruth E Westenbroek
Worldwide medicinal use of cannabis is rapidly escalating, despite limited evidence of its efficacy from preclinical and clinical studies. Here we show that cannabidiol (CBD) effectively reduced seizures and autistic-like social deficits in a well-validated mouse genetic model of Dravet syndrome (DS), a severe childhood epilepsy disorder caused by loss-of-function mutations in the brain voltage-gated sodium channel NaV 1.1. The duration and severity of thermally induced seizures and the frequency of spontaneous seizures were substantially decreased...
October 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28954820/cannabidiol-and-palmitoylethanolamide-are-anti-inflammatory-in-the-acutely-inflamed-human-colon
#16
Daniel G Couch, Chris Tasker, Elena Theophilidou, Jonathan N Lund, Saoirse E O'Sullivan
OBJECTIVE: We sought to quantify the anti-inflammatory effects of two cannabinoid drugs, cannabidiol (CBD) and palmitoylethanolamide (PEA), in cultured cell lines and compared this effect with experimentally inflamed explant human colonic tissue. These effects were explored in acutely and chronically inflamed colon, using inflammatory bowel disease and appendicitis explants. DESIGN: Caco-2 cells and human colonic explants collected from elective bowel cancer, inflammatory bowel disease (IBD) or acute appendicitis resections, and were treated with the following drug treatments: vehicle, an inflammatory protocol of interferon γ (IFNγ) and tumour necrosis factor α (TNFα; 10 ng/ml), inflammation and PEA (10 µM), inflammation and CBD (10 µM), and PEA or CBD alone, CBD or vehicle were added simultaneously with IFNγ...
November 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28875496/g-protein-coupled-receptor-gpr55-promotes-colorectal-cancer-and-has-opposing-effects-to-cannabinoid-receptor-1
#17
Carina Hasenoehrl, David Feuersinger, Eva M Sturm, Thomas Bärnthaler, Ellen Heitzer, Ricarda Graf, Magdalena Grill, Martin Pichler, Stephan Beck, Lee Butcher, Dominique Thomas, Nerea Ferreirós, Rufina Schuligoi, Caroline Schweiger, Johannes Haybaeck, Rudolf Schicho
The putative cannabinoid receptor GPR55 has been shown to play a tumor-promoting role in various cancers, and is involved in many physiological and pathological processes of the gastrointestinal (GI) tract. While the cannabinoid receptor 1 (CB1 ) has been reported to suppress intestinal tumor growth, the role of GPR55 in the development of GI cancers is unclear. We, therefore, aimed at elucidating the role of GPR55 in colorectal cancer (CRC), the third most common cancer worldwide. Using azoxymethane (AOM)- and dextran sulfate sodium (DSS)-driven CRC mouse models, we found that GPR55 plays a tumor-promoting role that involves alterations of leukocyte populations, i...
January 1, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28867485/mechanisms-of-action-of-cannabidiol-in-adoptively-transferred-experimental-autoimmune-encephalomyelitis
#18
Coral González-García, Irene Moreno Torres, Ruth García-Hernández, Lucía Campos-Ruíz, Luis Rodríguez Esparragoza, María José Coronado, Aranzazu García Grande, Antonio García-Merino, Antonio J Sánchez López
Cannabidiol (CBD) is one of the most important compounds in Cannabis sativa, lacks psychotropic effects, and possesses a high number of therapeutic properties including the amelioration of experimental autoimmune encephalomyelitis (EAE). The aim of this study was to analyse the relative efficacy of CBD in adoptively transferred EAE (at-EAE), a model that allows better delineation of the effector phase of EAE. Splenocytes and lymph nodes from mice with actively induced EAE were cultured in the presence of MOG35-55 and IL-12 and inoculated intraperitoneally in recipient female C57BL/6J mice...
December 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28861501/palmitoylethanolamide-modulates-gpr55-receptor-signaling-in-the-ventral-hippocampus-to-regulate-mesolimbic-dopamine-activity-social-interaction-and-memory-processing
#19
Cecilia Kramar, Michael Loureiro, Justine Renard, Steven R Laviolette
Introduction: The GPR55 receptor has been identified as an atypical cannabinoid receptor and is implicated in various physiological processes. However, its functional role in the central nervous system is not currently understood. The presence of GPR55 receptor in neural regions such as the ventral hippocampus (vHipp), which is critical for cognition, recognition memory, and affective processing, led us to hypothesize that intra-vHipp GPR55 transmission may modulate mesolimbic activity states and related behavioral phenomena...
2017: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/28826543/cannabinoids-and-pain-sites-and-mechanisms-of-action
#20
REVIEW
Katarzyna Starowicz, David P Finn
The endocannabinoid system, consisting of the cannabinoid1 receptor (CB1 R) and cannabinoid2 receptor (CB2 R), endogenous cannabinoid ligands (endocannabinoids), and metabolizing enzymes, is present throughout the pain pathways. Endocannabinoids, phytocannabinoids, and synthetic cannabinoid receptor agonists have antinociceptive effects in animal models of acute, inflammatory, and neuropathic pain. CB1 R and CB2 R located at peripheral, spinal, or supraspinal sites are important targets mediating these antinociceptive effects...
2017: Advances in Pharmacology
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