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https://www.readbyqxmd.com/read/29745439/cannabinoids-and-gastrointestinal-motility-pharmacology-clinical-effects-and-potential-therapeutics-in-humans
#1
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/29729263/enhanced-endocannabinoid-tone-as-a-potential-target-of-pharmacotherapy
#2
REVIEW
Marek Toczek, Barbara Malinowska
The endocannabinoid system is up-regulated in numerous pathophysiological states such as inflammatory, neurodegenerative, gastrointestinal, metabolic and cardiovascular diseases, pain, and cancer. It has been suggested that this phenomenon primarily serves an autoprotective role in inhibiting disease progression and/or diminishing signs and symptoms. Accordingly, enhancement of endogenous endocannabinoid tone by inhibition of endocannabinoid degradation represents a promising therapeutic approach for the treatment of many diseases...
May 2, 2018: Life Sciences
https://www.readbyqxmd.com/read/29725299/octadecylpropyl-sulfamide-reduces-neurodegeneration-and-restores-the-memory-deficits-induced-by-hypoxia-ischemia-in-mice
#3
Elk Kossatz, Daniel Silva-Peña, Juan Suárez, Fernando R de Fonseca, Rafael Maldonado, Patricia Robledo
The PPAR-α agonist, oleoylethanolamide (OEA) has neuroprotective properties in stroke models. However, its rapid degradation represents a limitation for an effective therapeutic approach. In this study, we evaluated the effects of a stable OEA-modeled compound, octadecylpropyl sulfamide (SUL) on the cognitive, behavioral, cellular and molecular alterations associated with hypoxia-ischemia (HI) in mice. Mice subjected to HI were treated with the PPAR-α antagonist GW6471 (GW) (1 mg/kg) followed 15 min later by SUL (3 and 10 mg/kg)...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29695817/therapeutic-endocannabinoid-augmentation-for-mood-and-anxiety-disorders-comparative-profiling-of-faah-magl-and-dual-inhibitors
#4
Gaurav Bedse, Rebecca J Bluett, Toni A Patrick, Nicole K Romness, Andrew D Gaulden, Philip J Kingsley, Niels Plath, Lawrence J Marnett, Sachin Patel
Recent studies have demonstrated anxiolytic potential of pharmacological endocannabinoid (eCB) augmentation approaches in a variety of preclinical models. Pharmacological inhibition of endocannabinoid-degrading enzymes, such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), elicit promising anxiolytic effects in rodent models with limited adverse behavioral effects, however, the efficacy of dual FAAH/MAGL inhibition has not been investigated. In the present study, we compared the effects of FAAH (PF-3845), MAGL (JZL184) and dual FAAH/MAGL (JZL195) inhibitors on (1) anxiety-like behaviors under non-stressed and stressed conditions, (2) locomotor activity and body temperature, (3) lipid levels in the brain and (4) cognitive functions...
April 26, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29665166/silencing-synaptic-microrna-411-reduces-voluntary-alcohol-consumption-in-mice
#5
Dana Most, Nihal A Salem, Gayatri R Tiwari, Yuri A Blednov, R Dayne Mayfield, R Adron Harris
Chronic alcohol consumption alters the levels of microRNAs and mRNAs in the brain, but the specific microRNAs and processes that target mRNAs to affect cellular function and behavior are not known. We examined the in vivo manipulation of previously identified alcohol-responsive microRNAs as potential targets to reduce alcohol consumption. Silencing of miR-411 by infusing antagomiR-411 into the prefrontal cortex of female C57BL/6J mice reduced alcohol consumption and preference, without altering total fluid consumption, saccharin consumption, or anxiety-related behaviors...
April 17, 2018: Addiction Biology
https://www.readbyqxmd.com/read/29660628/transcriptional-abundance-of-type-1-endocannabinoid-receptor-cb1-and-fatty-acid-amide-hydrolase-faah-in-bull-spermatozoa-relationship-with-field-fertility
#6
Vimlesh Kumar, Arumugam Kumaresan, Pradeep Nag, Puneeth Kumar, Tirtha Kumar Datta, Rubina Kumari Baithalu, Tushar Kumar Mohanty
A highly sophisticated endogenous cannabinoid system (ECS) has been shown to play a crucial role in controlling sperm functions and fertility in men. In the present study, we report the differences in the expression level of components of ECS [type-1 endocannabinoid receptor (CB1) and fatty acid amide hydrolase (FAAH)] in spermatozoa from bulls with different field fertility ratings. Cryopreserved spermatozoa from crossbred cattle bulls (n = 40) were utilized for the study. The bulls were classified into high-, medium- and low-fertile bulls based on field conception rates...
April 8, 2018: Theriogenology
https://www.readbyqxmd.com/read/29652995/-association-of-polymorphisms-of-nape-pld-and-faah-genes-with-schizophrenia-in-chinese-han-population
#7
Peiru Si, Shulian Liu, Dongxiao Tong, Meijin Cheng, Liwen Wang, Xiaoli Cheng
OBJECTIVE: To assess the association of polymorphisms of N-acyl-phosphatidylethanolamine-phospholipase D (DAPE-PLD) and fatty acid amide hydrolase (FAAH) genes, as well as their interaction, with schizophrenia. METHODS: Polymorphisms of NAPE-PLD rs12540583 and FAAH rs324420, rs2295633, and rs6429600 were determined with PCR - restriction fragment length polymorphism assay and Sanger sequencing. The genotypes of 345 subjects of Han Chinese origin diagnosed with schizophrenia and a 403 controls were compared...
April 10, 2018: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/29627605/evaluation-of-bisphenol-a-influence-on-endocannabinoid-system-in-pregnant-women
#8
Monika Zbucka-Kretowska, Robert Zbucki, Ewa Parfieniuk, Maciej Maslyk, Urszula Lazarek, Wojciech Miltyk, Jan Czerniecki, Slawomir Wolczynski, Adam Kretowski, Michal Ciborowski
Bisphenol A (BPA) is a synthetic chemical widely used in the industry, which may potentially evoke negative effects on human health, especially on reproductive processes and fetal development. BPA has been reported to act on estrogen, estrogen-related, androgen, thyroid hormone, pregnane X, peroxisome proliferation-activated, and aryl hydrocarbon receptors. However, other potential mechanisms of BPA action on pregnancy cannot be excluded. Comprehensive evaluation of BPA effect on pregnant women can be performed by use of metabolomics...
March 30, 2018: Chemosphere
https://www.readbyqxmd.com/read/29621749/the-endocannabinoid-system-affects-myocardial-glucose-metabolism-in-the-doca-salt-model-of-hypertension
#9
Agnieszka Polak, Ewa Harasim-Symbor, Barbara Malinowska, Irena Kasacka, Alicja Lewandowska, Adrian Chabowski
BACKGROUND/AIMS: Recent interest in the use of cannabinoids as therapeutic agents has revealed the involvement of the endogenous cannabinoid system (ECS) in the regulation of the cardiovascular system in hypertension. Abnormalities in glucose metabolism and insulin action are commonly detected in hypertensive animals. Thus, potential antihypertensive drugs should be investigated with respect to modulation of glucose homeostasis. Therefore, the aim of the present study was to evaluate the effects of the ECS activation after chronic fatty acid amide hydrolase inhibitor (URB597) administration on plasma glucose and insulin concentrations as well as parameters of myocardial glucose metabolism in the deoxycorticosterone acetate (DOCA)-salt hypertensive rats, an animal model of secondary hypertension...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29615860/endocannabinoid-system-and-migraine-pain-an-update
#10
REVIEW
Rosaria Greco, Chiara Demartini, Anna M Zanaboni, Daniele Piomelli, Cristina Tassorelli
The trigeminovascular system (TS) activation and the vasoactive release from trigeminal endings, in proximity of the meningeal vessels, are considered two of the main effector mechanisms of migraine attacks. Several other structures and mediators are involved, however, both upstream and alongside the TS. Among these, the endocannabinoid system (ES) has recently attracted considerable attention. Experimental and clinical data suggest indeed a link between dysregulation of this signaling complex and migraine headache...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29593494/antiepileptogenic-effect-of-subchronic-palmitoylethanolamide-treatment-in-a-mouse-model-of-acute-epilepsy
#11
Julia M Post, Sebastian Loch, Raissa Lerner, Floortje Remmers, Ermelinda Lomazzo, Beat Lutz, Laura Bindila
Research on the antiepileptic effects of (endo-)cannabinoids has remarkably progressed in the years following the discovery of fundamental role of the endocannabinoid (eCB) system in controlling neural excitability. Moreover, an increasing number of well-documented cases of epilepsy patients exhibiting multi-drug resistance report beneficial effects of cannabis use. Pre-clinical and clinical research has increasingly focused on the antiepileptic effectiveness of exogenous administration of cannabinoids and/or pharmacologically induced increase of eCBs such as anandamide (also known as arachidonoylethanolamide [AEA])...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29575526/fatty-acid-amide-hydrolase-inhibition-by-jnj-42165279-a-multiple-ascending-dose-and-a-positron-emission-tomography-study-in-healthy-volunteers
#12
Andrey Postnov, Mark E Schmidt, Darrel J Pemberton, Jan de Hoon, Anne van Hecken, Maarten van den Boer, Peter Zannikos, Peter van der Ark, James A Palmer, Stef Rassnick, Sofie Celen, Guy Bormans, Koen van Laere
Inhibition of fatty acid amide hydrolase (FAAH) potentiates endocannabinoid activity and is hypothesized to have therapeutic potential for mood and anxiety disorders and pain. The clinical profile of JNJ-42165279, an oral selective FAAH inhibitor, was assessed by investigating the pharmacokinetics, pharmacodynamics, safety, and binding to FAAH in the brain of healthy human volunteers. Concentrations of JNJ-42165279 (plasma, cerebrospinal fluid (CSF), urine) and fatty acid amides (FAA; plasma, CSF), and FAAH activity in leukocytes was determined in a phase I multiple ascending dose study...
March 25, 2018: Clinical and Translational Science
https://www.readbyqxmd.com/read/29573455/comparative-in-vitro-and-in-vivo-effects-of-chlorpyrifos-oxon-in-the-outbred-cd-1-mouse-mus-musculus-and-great-plains-toad-anaxyrus-cognatus
#13
Tim Anderson, Jing Liu, Scott McMurry, Carey Pope
We compared biochemical, functional and behavioral responses to the organophosphorus anticholinesterase chlorpyrifos oxon (CPO) in mice (Mus musculus, CD-1) and toads (Anaxyrus cognatus, Great Plains toad). Toads were substantially less sensitive to acute lethality of CPO based on the maximum tolerated (nonlethal) dose (MTD: toads, 77 mg/kg; mice, 5.9 mg/kg). Sublethal exposures led to classical signs of toxicity (increased involuntary movements, autonomic secretions) in mice, but hypo-activity in toads...
March 24, 2018: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/29562280/the-use-of-cannabinoids-in-colitis-a-systematic-review-and-meta-analysis
#14
Daniel G Couch, Henry Maudslay, Brett Doleman, Jonathan N Lund, Saoirse E O'Sullivan
Background: Clinical trials investigating the use of cannabinoid drugs for the treatment of intestinal inflammation are anticipated secondary to preclinical literature demonstrating efficacy in reducing inflammation. Methods: We systematically reviewed publications on the benefit of drugs targeting the endo-cannabinoid system in intestinal inflammation. We collated studies examining outcomes for meta-analysis from EMBASE, MEDLINE and Pubmed until March 2017. Quality was assessed according to mSTAIR and SRYCLE score...
March 19, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29542183/endocannabinoids-as-endometrial-inflammatory-markers-in-lactating-holstein-cows
#15
R Bonsale, R Seyed Sharifi, E Dirandeh, N Hedayat, A Mojtahedin, M Ghorbanalinia, A Abolghasemi
The objective of this study was to consider endocannabinoid system as inflammatory markers in bovine endometrium to better understand the role of this system in regulating many of the functions that are related to inflammatory condition. At day 26 post-partum, fourteen cows were divided into two groups depending on the inflammatory condition: 1- subclinical endometritis (n = 7, with purulent or mucopurulent uterine discharge detectable in the vagina) and 2- healthy (n = 7, No (muco)) purulent discharge...
March 14, 2018: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/29531281/author-correction-the-faah-inhibitor-urb597-suppresses-hippocampal-maximal-dentate-afterdischarges-and-restores-seizure-induced-impairment-of-short-and-long-term-synaptic-plasticity
#16
Roberto Colangeli, Massimo Pierucci, Arcangelo Benigno, Giuseppe Campiani, Stefania Butini, Giuseppe Di Giovanni
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
March 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29528965/evaluation-of-different-drug-classes-on-transient-sciatic-nerve-injury-depressed-marble-burying-in-mice
#17
Jenny L Wilkerson, Zachary A Curry, Pamela D Kinlow, Brittany L Mason, Ku-Lung Hsu, Mario van der Stelt, Benjamin F Cravatt, Aron H Lichtman
A great need exists for the identification of new effective analgesics to treat sustained pain. However, most preclinical nociceptive assays measure behavioral responses evoked by noxious stimuli (i.e., pain-stimulated behavior), which presents a challenge to distinguish between motor impairing and antinociceptive effects of drugs. Here, we demonstrate that chronic constriction injury of the sciatic nerve (CCI) elicits common pain-stimulated responses (i.e., mechanical allodynia and thermal hyperalgesia) as well as reduces marble burying/digging behaviors that occur during the early stages of the neuropathy and resolve within one week...
March 8, 2018: Pain
https://www.readbyqxmd.com/read/29519609/chronic-treatment-with-urb597-ameliorates-post-stress-symptoms-in-a-rat-model-of-ptsd
#18
Sharon Fidelman, Tomer Mizrachi Zer-Aviv, Rachel Lange, Cecilia J Hillard, Irit Akirav
Activating the endocannabinoid system has become a major focus in the search for novel therapeutics for anxiety and deficits in fear extinction, two defining features of PTSD. We examined whether chronic treatment with the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.2, 0.3, 0.4 mg/kg, i.p.) or the CB1/2 receptor agonist WIN55,212-2 (0.25, 0.5 mg/kg, i.p.) injected for 3 weeks to rats exposed to the shock and reminders model of PTSD would attenuate post-stress symptoms and affect basolateral amygdala (BLA) and CA1 CB1 receptors...
May 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29510186/the-anxiolytic-effects-of-cannabidiol-in-chronically-stressed-mice-are-mediated-by-the-endocannabinoid-system-role-of-neurogenesis-and-dendritic-remodeling
#19
Manoela V Fogaça, Alline C Campos, Ludmila D Coelho, Ronald S Duman, Francisco S Guimarães
Repeated injections of cannabidiol (CBD), the major non-psychotomimetic compound present in the Cannabis sativa plant, attenuate the anxiogenic effects induced by Chronic Unpredictable Stress (CUS). The specific mechanisms remain to be fully understood but seem to involve adult hippocampal neurogenesis and recruitment of endocannabinoids. Here we investigated for the first time if the behavioral and pro-neurogenic effects of CBD administered concomitant the CUS procedure (14 days) are mediated by CB1 , CB2 or 5HT1A receptors, as well as CBD effects on dendritic remodeling and on intracellular/synaptic signaling (fatty acid amide hydrolase - FAAH, Akt, GSK3β and the synaptic proteins Synapsin Ia/b, mGluR1 and PSD95)...
March 3, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29501385/endocannabinoid-tone-regulates-human-sebocyte-biology
#20
Nóra Zákány, Attila Oláh, Arnold Markovics, Erika Takács, Andrea Aranyász, Simon Nicolussi, Fabiana Piscitelli, Marco Allarà, Ágnes Pór, Ilona Kovács, Christos C Zouboulis, Jürg Gertsch, Vincenzo Di Marzo, Tamás Bíró, Tamás Szabó
We have previously shown that endocannabinoids (eCBs) (e.g., anandamide) are involved in the maintenance of homeostatic sebaceous lipid production in human sebaceous glands and that eCB treatment dramatically increases sebaceous lipid production. Here, we aimed to investigate the expression of the major eCB synthesizing and degrading enzymes and to study the effects of eCB uptake inhibitors on human SZ95 sebocytes, thus exploring the role of the putative eCB membrane transporter, which has been hypothesized to facilitate the cellular uptake and subsequent degradation of eCBs...
March 6, 2018: Journal of Investigative Dermatology
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