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https://www.readbyqxmd.com/read/27858284/role-of-cannabinoid-receptor-1-in-human-adipose-tissue-for-lipolysis-regulation-and-insulin-resistance
#1
Cherno O Sidibeh, Maria J Pereira, Joey Lau Börjesson, Prasad G Kamble, Stanko Skrtic, Petros Katsogiannos, Magnus Sundbom, Maria K Svensson, Jan W Eriksson
We recently showed that the peripheral cannabinoid receptor type 1 (CNR1) gene is upregulated by the synthetic glucocorticoid dexamethasone. CNR1 is highly expressed in the central nervous system and has been a drug target for the treatment of obesity. Here we explore the role of peripheral CNR1 in states of insulin resistance in human adipose tissue. Subcutaneous adipose tissue was obtained from well-controlled type 2 diabetes subjects and controls. Subcutaneous adipose tissue gene expression levels of CNR1 and endocannabinoid synthesizing and degrading enzymes were assessed...
November 17, 2016: Endocrine
https://www.readbyqxmd.com/read/27762084/variants-in-the-cnr1-gene-predispose-to-headache-with-nausea-in-the-presence-of-life-stress
#2
Gabriella Juhasz, Eva Csepany, Mate Magyar, Andrea Edit Edes, Nora Eszlari, Gabor Hullam, Peter Antal, Gyongyi Kokonyei, Ian Muir Anderson, John Francis William Deakin, Gyorgy Bagdy
One of the main effects of the endocannabinoid system in the brain is stress adaptation with presynaptic endocannabinoid receptor 1 (CB1 receptors) playing a major role. In the present study, we investigated whether the effect of the CB1 receptor coding CNR1 gene on migraine and its symptoms is conditional on life stress. In a cross-sectional European population (n = 2426), recruited from Manchester and Budapest, we used the ID-Migraine questionnaire for migraine screening, the Life Threatening Experiences questionnaire to measure recent negative life events (RLE), and covered the CNR1 gene with 11 SNPs...
October 19, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27613640/spontaneous-involution-of-pediatric-low-grade-gliomas-high-expression-of-cannabinoid-receptor-1-cnr1-at-the-time-of-diagnosis-may-indicate-involvement-of-the-endocannabinoid-system
#3
Simone Treiger Sredni, Chiang-Ching Huang, Mario Suzuki, Tatiana Pundy, Pauline Chou, Tadanori Tomita
BACKGROUND: Pediatric low-grade gliomas (P-LGG) consist of a mixed group of brain tumors that correspond to the majority of CNS tumors in children. Notably, they may exhibit spontaneous involution after subtotal surgical removal (STR). In this study, we investigated molecular indicators of spontaneous involution in P-LGG. METHODS: We performed an integrated molecular analysis including high throughput gene expression (GE), microRNA (miRNA) expression data of primary, untreated tumors from patients with P-LGG who underwent STR at our institution, with at least 10 years follow-up...
September 9, 2016: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/27525312/hybrid-inhibitor-of-peripheral-cannabinoid-1-receptors-and-inducible-nitric-oxide-synthase-mitigates-liver-fibrosis
#4
Resat Cinar, Malliga R Iyer, Ziyi Liu, Zongxian Cao, Tony Jourdan, Katalin Erdelyi, Grzegorz Godlewski, Gergő Szanda, Jie Liu, Joshua K Park, Bani Mukhopadhyay, Avi Z Rosenberg, Jeih-San Liow, Robin G Lorenz, Pal Pacher, Robert B Innis, George Kunos
Liver fibrosis, a consequence of chronic liver injury and a way station to cirrhosis and hepatocellular carcinoma, lacks effective treatment. Endocannabinoids acting via cannabinoid-1 receptors (CB1R) induce profibrotic gene expression and promote pathologies that predispose to liver fibrosis. CB1R antagonists produce opposite effects, but their therapeutic development was halted due to neuropsychiatric side effects. Inducible nitric oxide synthase (iNOS) also promotes liver fibrosis and its underlying pathologies, but iNOS inhibitors tested to date showed limited therapeutic efficacy in inflammatory diseases...
July 21, 2016: JCI Insight
https://www.readbyqxmd.com/read/27500453/lifetime-use-of-cannabis-from-longitudinal-assessments-cannabinoid-receptor-cnr1-variation-and-reduced-volume-of-the-right-anterior-cingulate
#5
Shirley Y Hill, Vinod Sharma, Bobby L Jones
Lifetime measures of cannabis use and co-occurring exposures were obtained from a longitudinal cohort followed an average of 13 years at the time they received a structural MRI scan. MRI scans were analyzed for 88 participants (mean age=25.9 years), 34 of whom were regular users of cannabis. Whole brain voxel based morphometry analyses (SPM8) were conducted using 50 voxel clusters at p=0.005. Controlling for age, familial risk, and gender, we found reduced volume in Regular Users compared to Non-Users, in the lingual gyrus, anterior cingulum (right and left), and the rolandic operculum (right)...
September 30, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/27469238/pharmacogenetics-of-tardive-dyskinesia-an-updated-review-of-the-literature
#6
Rachel K Lanning, Clement C Zai, Daniel J Müller
Tardive dyskinesia (TD) is a serious and potentially irreversible side effect of long-term exposure to antipsychotic medication characterized by involuntary trunk, limb and orofacial muscle movements. Various mechanisms have been proposed for the etiopathophysiology of antipsychotic-induced TD in schizophrenia patients with genetic factors playing a prominent role. Earlier association studies have focused on polymorphisms in CYP2D6, dopamine-, serotonin-, GABA- and glutamate genes. This review highlights recent advances in the genetic investigation of TD...
August 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27453054/cannabinoid-receptor-1-cnr1-gene-variant-moderates-neural-index-of-cognitive-disruption-during-nicotine-withdrawal
#7
D E Evans, S K Sutton, K G Jentink, H-Y Lin, J Y Park, D J Drobes
Nicotine withdrawal-related disruption of cognitive control may contribute to the reinforcement of tobacco use. Identification of gene variants that predict this withdrawal phenotype may lead to tailored pharmacotherapy for smoking cessation. Variation on the cannabinoid receptor 1 gene (CNR1) has been related to nicotine dependence, and CNR1 antagonists may increase attention and memory functioning. We targeted CNR1 variants as moderators of a validated neural marker of nicotine withdrawal-related cognitive disruption...
September 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27401043/mechanical-and-material-properties-of-cortical-and-trabecular-bone-from-cannabinoid-receptor-1-null-cnr1-mice
#8
Aysha B Khalid, Simon R Goodyear, Ruth A Ross, Richard M Aspden
The endocannabinoid system is known for its regulatory effects on bone metabolism through the cannabinoid receptors, Cnr1 and Cnr2. In this study we analysed the mechanical and material properties of long bones from Cnr1(-/-) mice on a C57BL/6 background. Tibiae and femora from 5- and 12-week-old mice were subjected to three-point bending to measure bending stiffness and yield strength. Elastic modulus, density and mineral content were measured in the diaphysis. Second moment of area (MOA2), inner and outer perimeters of the cortical shaft and trabecular fractional bone volume (BV/TV) were measured using micro-CT...
October 2016: Medical Engineering & Physics
https://www.readbyqxmd.com/read/27394933/genetic-variation-in-faah-is-associated-with-cannabis-use-disorders-in-a-young-adult-sample-of-mexican-americans
#9
Whitney E Melroy-Greif, Kirk C Wilhelmsen, Cindy L Ehlers
BACKGROUND: Cannabis is a commonly used drug and studies have shown that a significant portion of the variation in cannabis use disorders (CUDs) is heritable. Five genes known to play a role in the endocannabinoid system and CUDs were examined in a community sample of young adult Mexican Americans (MAs): CNR1, MGLL, FAAH, DAGLA, and DAGLB. METHODS: Gene-based tests were run to test for association between each gene and two DSM-5 cannabis phenotypes. Subsequent linear regressions were run in PLINK using an additive model to determine which single nucleotide polymorphisms (SNPs) were driving the association...
September 1, 2016: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/27346075/genetic-variation-in-the-endocannabinoid-system-and-response-to-cognitive-behavior-therapy-for-child-anxiety-disorders
#10
Kathryn J Lester, Jonathan R I Coleman, Susanna Roberts, Robert Keers, Gerome Breen, Susan Bögels, Cathy Creswell, Jennifer L Hudson, Anna McKinnon, Maaike Nauta, Ronald M Rapee, Silvia Schneider, Wendy K Silverman, Mikael Thastum, Polly Waite, Gro Janne H Wergeland, Thalia C Eley
Extinction learning is an important mechanism in the successful psychological treatment of anxiety. Individual differences in response and relapse following Cognitive Behavior Therapy may in part be explained by variability in the ease with which fears are extinguished or the vulnerability of these fears to re-emerge. Given the role of the endocannabinoid system in fear extinction, this study investigates whether genetic variation in the endocannabinoid system explains individual differences in response to CBT...
June 27, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/27327781/the-endocannabinoid-system-in-the-baboon-papio-spp-as-a-complex-framework-for-developmental-pharmacology
#11
Iram P Rodriguez-Sanchez, Josee Guindon, Marco Ruiz, Maria E Tejero, Gene Hubbard, Laura E Martinez-de-Villarreal, Hugo A Barrera-Saldaña, Edward J Dick, Anthony G Commuzzie, Natalia E Schlabritz-Loutsevitch
INTRODUCTION: The consumption of marijuana (exogenous cannabinoid) almost doubled in adults during last decade. Consumption of exogenous cannabinoids interferes with the endogenous cannabinoid (or "endocannabinoid" (eCB)) system (ECS), which comprises N-arachidonylethanolamide (anandamide, AEA), 2-arachidonoyl glycerol (2-AG), endocannabinoid receptors (cannabinoid receptors 1 and 2 (CB1R and CB2R), encoded by CNR1 and CNR2, respectively), and synthesizing/degrading enzymes (FAAH, fatty-acid amide hydrolase; MAGL, monoacylglycerol lipase; DAGL-α, diacylglycerol lipase-alpha)...
June 17, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27305347/autophagy-activation-by-novel-inducers-prevents-becn2-mediated-drug-tolerance-to-cannabinoids
#12
Kenta Kuramoto, Nan Wang, Yuying Fan, Weiran Zhang, Frank J Schoenen, Kevin J Frankowski, Juan Marugan, Yifa Zhou, Sui Huang, Congcong He
Cannabinoids and related drugs generate profound behavioral effects (such as analgesic effects) through activating CNR1 (cannabinoid receptor 1 [brain]). However, repeated cannabinoid administration triggers lysosomal degradation of the receptor and rapid development of drug tolerance, limiting the medical use of marijuana in chronic diseases. The pathogenic mechanisms of cannabinoid tolerance are not fully understood, and little is known about its prevention. Here we show that a protein involved in macroautophagy/autophagy (a conserved lysosomal degradation pathway), BECN2 (beclin 2), mediates cannabinoid tolerance by preventing CNR1 recycling and resensitization after prolonged agonist exposure, and deletion of Becn2 rescues CNR1 activity in mouse brain and conveys resistance to analgesic tolerance to chronic cannabinoids...
September 2016: Autophagy
https://www.readbyqxmd.com/read/27261878/prefrontal-activity-during-working-memory-is-modulated-by-the-interaction-of-variation-in-cb1-and-cox2-coding-genes-and-correlates-with-frequency-of-cannabis-use
#13
Paolo Taurisano, Linda A Antonucci, Leonardo Fazio, Antonio Rampino, Raffaella Romano, Annamaria Porcelli, Rita Masellis, Marco Colizzi, Tiziana Quarto, Silvia Torretta, Annabella Di Giorgio, Giulio Pergola, Alessandro Bertolino, Giuseppe Blasi
The CB1 cannabinoid receptor is targeted in the brain by endocannabinoids under physiological conditions as well as by delta9-tetrahydrocannabinol under cannabis use. Furthermore, its signaling appears to affect brain cognitive processing. Recent findings highlight a crucial role of cyclooxygenase-2 (COX-2) in the mechanism of intraneuronal CB1 signaling transduction, while others indicate that two single nucleotide polymorphisms (SNPs) (rs1406977 and rs20417) modulate expression of CB1 (CNR1) and COX-2 (PTGS2) coding genes, respectively...
August 2016: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
https://www.readbyqxmd.com/read/27260125/pharmacological-characterization-of-emerging-synthetic-cannabinoids-in-hek293t-cells-and-hippocampal-neurons
#14
Willard J Costain, Joseph S Tauskela, Ingrid Rasquinha, Tanya Comas, Melissa Hewitt, Vincent Marleau, Evelyn C Soo
There has been a worldwide proliferation of synthetic cannabinoids that have become marketed as legal alternatives to cannabis (marijuana). Unfortunately, there is a dearth of information about the pharmacological effects of many of these emerging synthetic cannabinoids (ESCs), which presents a challenge for regulatory authorities that need to take such scientific evidence into consideration in order to regulate ECSs as controlled substances. We aimed to characterize the pharmacological properties of ten ESCs using two cell based assays that enabled the determination of potency and efficacy relative to a panel of well-characterized cannabinoids...
September 5, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27248492/cannabinoid-receptors-are-overexpressed-in-cll-but-of-limited-potential-for-therapeutic-exploitation
#15
Patricia Freund, Edit A Porpaczy, Trang Le, Michaela Gruber, Clemens Pausz, Philipp Staber, Ulrich Jäger, Katrina Vanura
The cannabinoid receptors 1 and 2 (CNR1&2) are overexpressed in a variety of malignant diseases and cannabinoids can have noteworthy impact on tumor cell viability and tumor growth. Patients diagnosed with chronic lymphocytic leukemia (CLL) present with very heterogeneous disease characteristics translating into highly differential risk properties. To meet the urgent need for refinement in risk stratification at diagnosis and the search for novel therapies we studied CNR expression and response to cannabinoid treatment in CLL...
2016: PloS One
https://www.readbyqxmd.com/read/27133395/the-role-of-the-endocannabinoid-system-in-the-brain-gut-axis
#16
REVIEW
Keith A Sharkey, John W Wiley
The actions of cannabis are mediated by receptors that are part of an endogenous cannabinoid system. The endocannabinoid system (ECS) consists of the naturally occurring ligands N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG), their biosynthetic and degradative enzymes, and the cannabinoid (CB) receptors CB1 and CB2. The ECS is a widely distributed transmitter system that controls gut functions peripherally and centrally. It is an important physiologic regulator of gastrointestinal motility...
August 2016: Gastroenterology
https://www.readbyqxmd.com/read/27108777/because-difficulty-is-not-the-same-for-everyone-the-impact-of-complexity-in-working-memory-is-associated-with-cannabinoid-1-receptor-genetic-variation-in-young-adults
#17
Alejandra E Ruiz-Contreras, Talía V Román-López, Ulises Caballero-Sánchez, Cintia B Rosas-Escobar, E Ivett Ortega-Mora, Miguel A Barrera-Tlapa, Sandra Romero-Hidalgo, Karol Carrillo-Sánchez, Salvador Hernández-Morales, Felipe Vadillo-Ortega, Juan Antonio González-Barrios, Mónica Méndez-Díaz, Oscar Prospéro-García
Individual differences in working memory ability are mainly revealed when a demanding challenge is imposed. Here, we have associated cannabinoid 1 (CB1) receptor genetic variation rs2180619 (AA, AG, GG), which is located in a potential CNR1 regulatory sequence, with performance in working memory. Two-hundred and nine Mexican-mestizo healthy young participants (89 women, 120 men, mean age: 23.26 years, SD = 2.85) were challenged to solve a medium (2-back) vs. a high (3-back) difficulty N-back tasks. All subjects responded as expected, performance was better with the medium than the high demand task version, but no differences were found among genotypes while performing each working memory (WM) task...
April 25, 2016: Memory
https://www.readbyqxmd.com/read/27074158/dose-dependent-cannabis-use-depressive-symptoms-and-faah-genotype-predict-sleep-quality-in-emerging-adults-a-pilot-study
#18
Kristin E Maple, Kymberly A McDaniel, Skyler G Shollenbarger, Krista M Lisdahl
BACKGROUND: Cannabis has been shown to affect sleep in humans. Findings from animal studies indicate that higher endocannabinoid levels promote sleep, suggesting that chronic use of cannabis, which downregulates endocannabinoid activity, may disrupt sleep. OBJECTIVES: This study sought to determine if past-year cannabis use and genes that regulate endocannabinoid signaling, FAAH rs324420 and CNR1 rs2180619, predicted sleep quality. As depression has been previously associated with both cannabis and sleep, the secondary aim was to determine if depressive symptoms moderated or mediated these relationships...
July 2016: American Journal of Drug and Alcohol Abuse
https://www.readbyqxmd.com/read/27034934/uremic-pruritus-is-not-associated-with-endocannabinoid-receptor-1-gene-polymorphisms
#19
Monika Heisig, Łukasz Łaczmański, Adam Reich, Felicja Lwow, Jacek C Szepietowski
Uremic pruritus (UP) is a frequent and bothersome symptom in hemodialysis patients. Its etiology is not fully understood and that is why there is no specific treatment. The endocannabinoid system plays a role in many pathological conditions. There is reliable evidence on the association between cannabinoid system and pruritus. In our study, we aimed to evaluate whether genetic variations in the endocannabinoid receptor 1 (CNR1) gene can affect UP. The rs12720071, rs806368, rs1049353, rs806381, rs10485170, rs6454674, and rs2023239 polymorphisms of the CNR1 gene were genotyped in 159 hemodialysis patients and 150 healthy controls using two multiplex polymerase chain reactions and the minisequencing technique...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27014939/bisphenol-a-induces-fatty-liver-by-an-endocannabinoid-mediated-positive-feedback-loop
#20
Andrea Martella, Cristoforo Silvestri, Francesca Maradonna, Giorgia Gioacchini, Marco Allarà, Giuseppe Radaelli, Darryl R Overby, Vincenzo Di Marzo, Oliana Carnevali
The xenoestrogen bisphenol A (BPA) is a widespread plasticizer detectable within several ecosystems. BPA is considered a metabolic disruptor, affecting different organs; however, little is known about its mechanism of action in the liver, in which it triggers triglyceride accumulation. Adult zebrafish (Danio rerio) exposed to BPA developed hepatosteatosis, which was associated with an increase in the liver levels of the obesogenic endocannabinoids 2-arachidonoylglycerol and anandamide and a concomitant decrease in palmitoylethanolamide...
May 2016: Endocrinology
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