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https://www.readbyqxmd.com/read/29458190/cannabinoids-prevent-depressive-like-symptoms-and-alterations-in-bdnf-expression-in-a-rat-model-of-ptsd
#1
Or Burstein, Noa Shoshan, Ravid Doron, Irit Akirav
Posttraumatic stress disorder (PTSD) is a debilitating condition highly comorbid with depression. The endocannabinoid (eCB) system and brain-derived neurotrophic factor (BDNF) are suggestively involved in both disorders. We examined whether cannabinoids can prevent the long-term depressive-like symptoms induced by exposure to the shock and situational reminders (SRs) model of PTSD. The CB1/2 receptor agonist WIN55,212-2 (0.5 mg/kg; i.p.), the fatty acid hydrolase (FAAH) inhibitor URB597 (0.3 mg/kg, i.p.) or vehicle were administered 2 h after severe shock...
February 16, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29457829/species-specific-susceptibility-to-cannabis-induced-convulsions
#2
Benjamin J Whalley, Hong Lin, Lynne Bell, Thomas Hill, Amesha Patel, Roy A Gray, C Elizabeth Roberts, Orrin Devinsky, Michael Bazelot, Claire M Williams, Gary J Stephens
BACKGROUND AND PURPOSE: Numerous claims are made for cannabis' therapeutic utility upon human seizures, but concerns persist about risks. A potential confounder is the presence of both Δ9 -tetrahydrocannabinol (Δ9 -THC), variously reported to be pro- and anti-convulsant, and cannabidiol (CBD), widely confirmed as anticonvulsant. Therefore, we investigated effects of prolonged exposure to different Δ9 -THC/CBD cannabis extracts on seizure activity and associated measures of endocannabinoid (eCB) system signalling...
February 19, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29456490/limited-access-to-a-high-fat-diet-alters-endocannabinoid-tone-in-female-rats
#3
Valentina Satta, Maria Scherma, Fabiana Piscitelli, Paolo Usai, M Paola Castelli, Tiziana Bisogno, Walter Fratta, Paola Fadda
Emerging evidence suggest an impaired endocannabinoid activity in the pathophysiology of binge eating disorder (BED). Herein, we investigated whether endocannabinoid tone could be modified as a consequence of dietary-induced binge eating in female rats. For this purpose, brain levels of the endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), as well as two endocannabinoid-like lipids, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), were assessed in different brain areas involved in the hedonic feeding (i...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29441900/role-of-the-endocannabinoid-system-in-the-formation-and-development-of-depression
#4
Dan Zhou, Yue Li, Tian Tian, Wei Quan, Lei Wang, Qing Shao, Lian-Qiang Fu, Xiao-Hong Zhang, Xiao-Ye Wang, Hui Zhang, Yan-Min Ma
Two types of cannabinoid (CB) receptors have been described in the human body: CB1 and CB2 receptors. CB1 receptor distribution may be related to the cannabinoid functions of memory and cognition regulation as well as motor control. In addition, the endocannabinoid system (ECS) related to CB1 receptors may be involved in human emotion regulation, especially depression occurrence. Indeed, CB1 receptors are all distributed in depression associated neuroanatomical structures and neural circuits. Both animal experiments and clinical studies have demonstrated that impairment of the ECS pathway is present in depression models and patients, and application of both CB1 receptor agonists and anandamide (cannabinoid-like substance) degradation inhibitors produce similar biochemical and behavioral effects as antidepressants...
August 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29432698/long-term-depression-induced-by-endogenous-cannabinoids-produces-neuroprotection-via-astroglial-cb1r-after-stroke-in-rodents
#5
Feng Wang, Jing Han, Haruki Higashimori, Jingyi Wang, Jingjing Liu, Li Tong, Yongjie Yang, Hailong Dong, Xia Zhang, Lize Xiong
Ischemia not only activates cell death pathways but also triggers endogenous protective mechanisms. However, it is largely unknown what is the essence of the endogenous neuroprotective mechanisms induced by preconditioning. In this study we demonstrated that systemic injection of JZL195, a selective inhibitor of eCB clearance enzymes, induces in vivo long-term depression at CA3-CA1 synapses and at PrL-NAc synapses produces neuroprotection. JZL195-elicited long-term depression is blocked by AM281, the antagonist of cannabinoid 1 receptor (CB1R) and is abolished in mice lacking cannabinoid CB1 receptor (CB1R) in astroglial cells, but is conserved in mice lacking CB1R in glutamatergic or GABAergic neurons...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29425797/antinociceptive-effects-of-the-endogenous-cannabinoid-peptide-agonist-vd-hemopressin-%C3%AE-in-mice
#6
Pei Wang, Ting Zheng, Mengna Zhang, Biao Xu, Run Zhang, Ting Zhang, Weidong Zhao, Xuerui Shi, Qinqin Zhang, Quan Fang
Cannabinoids (CBs) play important roles in pain modulation. Recently, VD-hemopressin(β) [VD-Hpβ], a 12-residue β-hemoglobin-derived peptide, was reported to activate both CB1 and CB2 receptors in vitro. To further characterize in vivo actions of VD-Hpβ, its antinociceptive activity and site(s) were evaluated in the mouse tail-flick test, and supraspinal antinociception of VD-Hpβ was further assessed in the writhing test. Our results demonstrated that supraspinal, intrathecal, subcutaneous and intraperitoneal administrations of VD-Hpβ produced analgesia in the tail-flick test...
February 6, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29424035/involvement-of-spinal-cannabinoid-receptors-in-the-antipruritic-effects-of-win-55-212-2-a-cannabinoid-receptor-agonist
#7
K A Bilir, G Anli, E Ozkan, O Gunduz, A Ulugol
BACKGROUND: Cannabinoids have been used for their analgesic and euphoric effects for millennia, but recently the antipruritic effects of cannabis have been discovered. Considering the similarities between pain and itch sensations, we hypothesized that cannabinoid receptors may play a role in the antipruritic effects of cannabinoids. AIM: To analyse the role of the spinal cannabinoid receptors, CB1 and CB2, in the antipruritic effects of the cannabinoid agonist WIN 55,212-2...
February 9, 2018: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/29419319/synthesis-and-biological-evaluation-of-ferrocene-based-cannabinoid-receptor-2-ligands
#8
Supojjanee Sansook, Wei Tuo, Mélanie Bollier, Amélie Barczyk, Xavier Dezitter, Fredérique Klupsch, Natascha Leleu-Chavain, Amaury Farce, Graham J Tizzard, Simon J Coles, John Spencer, Régis Millet
Ferrocene analogs of known fatty acid amide hydrolase inhibitors and CB2 ligands have been synthesized and characterized spectroscopically and crystallographically. The resulting bio-organometallic isoxazoles were assayed for their effects on CB1 and CB2 receptors as well as on fatty acid amide hydrolase. None had any fatty acid amide hydrolase activity but compound 3, 5-(2-(pentyloxy)phenyl)-N-ferrocenylisoxazole-3-carboxamide, was found to be a potent CB2 ligand (Ki = 32.5 nM).
February 8, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29417597/acute-ethanol-inhibition-of-adult-hippocampal-neurogenesis-involves-cb1-cannabinoid-receptor-signaling
#9
Dal Khatri, Genevieve Laroche, Marion L Grant, Victoria M Jones, Ryan P Vetreno, Fulton T Crews, Somnath Mukhopadhyay
BACKGROUND: Chronic ethanol exposure has been found to inhibit adult hippocampal neurogenesis in multiple models of alcohol addiction. However, acute ethanol inhibition of adult neurogenesis is not well studied. Although many abused drugs have been found to inhibit adult neurogenesis, few have studied cannabinoids or cannabinoids with ethanol, although human use of both together is becoming more common. We used an acute binge alcohol drinking model in combination with select cannabinoid receptor agonists and antagonists to investigate the actions of each alone and together on hippocampal neurogenesis...
February 8, 2018: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29413441/feasibility-evaluation-of-myocardial-cannabinoid-type-1-receptor-imaging%C3%A2-in%C3%A2-obesity-a-translational-approach
#10
Ines Valenta, Zoltan V Varga, Heather Valentine, Resat Cinar, Andrew Horti, William B Mathews, Robert F Dannals, Kimberley Steele, George Kunos, Richard L Wahl, Martin G Pomper, Dean F Wong, Pal Pacher, Thomas H Schindler
OBJECTIVES: The aim of this study was to evaluate the feasibility of targeted imaging of myocardial cannabinoid type 1 receptor (CB1-R) and its potential up-regulation in obese mice with translation to humans using [11C]-OMAR and positron emission tomography (PET)/computed tomography (CT). BACKGROUND: Activation of myocardial CB1-R by endocannabinoids has been implicated in cardiac dysfunction in diabetic mice. Obesity may lead to an up-regulation of myocardial CB1-R, potentially providing a mechanistic link between obesity and the initiation and/or progression of cardiomyopathy...
February 2018: JACC. Cardiovascular Imaging
https://www.readbyqxmd.com/read/29412125/the-endocannabinoid-system-and-heart-disease-the-role-of-cannabinoid-receptor-type-2
#11
Morad Hebi, Douglas P Thewke
Decades of research has provided evidence for the role of the endocannabinoid system in human health and disease. This versatile system, consisting of two receptors (CB1 and CB2), their endogenous ligands (endocannabinoids), and metabolic enzymes has been implicated in a wide variety of disease states, ranging from neurological disorders to cancer. CB2 has gained much interest for its beneficial immunomodulatory role that can be obtained without eliciting psychotropic effects through CB1. Recent studies have shed light on a protective role of CB2 in cardiovascular disease, an ailment which currently takes more lives each year in Western countries than any other disease or injury...
February 6, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/29410032/the-synthetic-cannabinoid-xlr-11-induces-in-vitro-nephrotoxicity-by-impairment-of-endocannabinoid-mediated-regulation-of-mitochondrial-function-homeostasis-and-triggering-of-apoptosis
#12
João P Silva, Helena Carmo, Félix Carvalho
Synthetic cannabinoids (SCBs)-related intoxications and deaths have been increasingly reported, turning its widespread recreational use into a major public health concern. Specifically, a direct link between SCBs and acute kidney injury (AKI) has been established. XLR-11 is an SCB commonly found in the toxicological analysis of patients with SCB-associated AKI. However, the pathophysiology of AKI among SCB consumers remains unknown. This work thus represents the first in vitro assessment of SCB nephrotoxicity, as a first approach to identify its cellular targets...
February 3, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29408093/analysis-of-the-pharmacological-properties-of-jwh-122-isomers-and-thj-2201-rcs-4-and-ab-chminaca-in-hek293t-cells-and-hippocampal-neurons
#13
Willard J Costain, Ingrid Rasquinha, Tanya Comas, Melissa Hewitt, Amy Aylsworth, Yanouchka Rouleau, Vincent Marleau, Evelyn C Soo, Joseph S Tauskela
Synthetic cannabinoids are marketed as legal alternatives to Δ9-THC, and are a growing worldwide concern as these drugs are associated with severe adverse effects. Unfortunately, insufficient information regarding the physiological and pharmacological effects of emerging synthetic cannabinoids (ESCs) makes their regulation by government authorities difficult. One strategy used to evade regulation is to distribute isomers of regulated synthetic cannabinoids. This study characterized the pharmacological properties of a panel of ESCs in comparison to Δ9-THC, as well as six JWH-122 isomers relative to its parent compound (JWH-122-4)...
February 2, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29407967/optimization-of-the-metabolic-stability-of-a-fluorinated-cannabinoid-receptor-subtype-2-cb2-ligand-designed-for-pet-studies
#14
Dominik Heimann, Frederik Börgel, Henk de Vries, Marius Patberg, Eliot Jan-Smith, Bastian Frehland, Dirk Schepmann, Laura H Heitman, Bernhard Wünsch
The central CB2 receptor represents a promising target for the treatment of neuroinflammatory diseases as CB2 activation mediates anti-inflammatory effects. Recently, the F-18 labeled PET radiotracer [18F]7a was reported, which shows high CB2 affinity and high selectivity over the CB1 subtype but low metabolic stability due to hydrolysis of the amide group. Based on these findings twelve bioisosteres of 7a were synthesized containing a non-hydrolysable functional group instead of the amide group. The secondary amine 23a (Ki = 7...
January 30, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29407764/rimonabant-a-potent-cb1-cannabinoid-receptor-antagonist-is-a-g%C3%AE-i-o-protein-inhibitor
#15
Alessandra Porcu, Miriam Melis, Rostislav Turecek, Celine Ullrich, Ignazia Mocci, Bernhard Bettler, Gian Luigi Gessa, M Paola Castelli
Rimonabant is a potent and selective cannabinoid CB1 receptor antagonist widely used in animal and clinical studies. Besides its antagonistic properties, numerous studies have shown that, at micromolar concentrations rimonabant behaves as an inverse agonist at CB1 receptors. The mechanism underpinning this activity is unclear. Here we show that micromolar concentrations of rimonabant inhibited Gαi/o-type G proteins, resulting in a receptor-independent block of G protein signaling. Accordingly, rimonabant decreased basal and agonist stimulated [35S]GTPγS binding to cortical membranes of CB1- and GABAB-receptor KO mice and Chinese Hamster Ovary (CHO) cell membranes stably transfected with GABAB or D2 dopamine receptors...
January 27, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29406831/contribution-of-spinal-5-ht5a-receptors-to-the-antinociceptive-effects-of-systemically-administered-cannabinoid-agonist-win-55-212-2-and-morphine
#16
Ahmet Goktan Aksu, Ozgur Gunduz, Ahmet Ulugol
The antinociceptive effects of cannabinoids and opioids have been known for centuries. Serotonin and its receptors are also known to play important roles in nociception. However, the contribution of spinal 5-HT5A receptors in antinociceptive effects of cannabinoids and opioids has not been studied. We conducted this study to clarify spinal mechanisms of the actions of the antinociceptive effects of cannabinoids and opioids. Hot-plate and tail-flick tests were used to assess the antinociceptive activity in Balb/c mice...
February 6, 2018: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29404698/novel-derivatives-of-1-2-3-triazole-cannabinoid-1-receptor-ligands-modulate-gastrointestinal-motility-in-mice
#17
Agata Szymaszkiewicz, Marta Zielinska, Kun Li, Mani Ramanathan, Safiul Alam, Duen-Ren Hou, Jakub Fichna, Martin Storr
Cannabinoid-1 (CB1) receptors are broadly distributed in the central and peripheral nervous systems; among others, they are located in the enteric nervous system. In the gastrointestinal (GI) system, they participate in regulation of intestinal motility or ion transport. The aim of our study was to assess the effect of 1,2,3-triazole derivatives (compound 1: 2-[4,5-bis(2,4-dichlorophenyl)-2H-1,2,3-triazol-2-yl]-N-(2-fluorobenzyl)acetamide, compound 2: 2-[4,5-bis(2,4-dichlorophenyl)-2H-1,2,3-triazol-2-yl]-N-(4-fluorobenzyl)acetamide, compound 3: N-benzyl-2-[4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2H-1,2,3-triazol-2-yl]acetamide]), characterized in vitro as CB1 antagonists with high CB1 over CB2 selectivity, in the mouse GI tract...
February 5, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29399584/evaluation-of-two-different-enzyme-linked-immunosorbent-assay-for-severe-fever-with-thrombocytopenia-syndrome-virus-diagnosis
#18
Min-Ah Yu, Hye Won Jeong, Su-Jin Park, Young-Il Kim, Hyeok-Il Kwon, Eun-Ha Kim, Young-Jae Si, Kwang Min Yu, Norbert John Robles, Hae Jung Han, Young Ki Choi
To develop the large scale serological assay for severe fever with thrombocytopenia syndrome virus (SFTSV) infection, we evaluated two different enzyme-linked immunosorbent assay (ELISA) methods using nucleocapsid protein (NP) and Gn proteins of CB1 (genotype B) SFTSV strains. The NP-based ELISA tests showed more sensitive with broad cross-reactivity between two different genotype A and B strains compared with those of Gn-based ELISA tests. However, Gn-based ELISA showed more genotype specificity and specificity...
January 2018: Clinical and Experimental Vaccine Research
https://www.readbyqxmd.com/read/29390896/targeting-the-endocannabinoid-system-as-a-potential-anticancer-approach
#19
Rico Schwarz, Robert Ramer, Burkhard Hinz
The endocannabinoid system is currently under intense investigation due to the therapeutic potential of cannabinoid-based drugs as treatment options for a broad variety of diseases including cancer. Besides the canonical endocannabinoid system that includes the cannabinoid receptors CB1 and CB2 and the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol, recent investigations suggest that other fatty acid derivatives, receptors, enzymes, and lipid transporters likewise orchestrate this system as components of the endocannabinoid system when defined as an extended signaling network...
February 1, 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29388323/effects-of-repeated-long-term-psychosocial-stress-and-acute-cannabinoid-exposure-on-mouse-corticostriatal-circuitries-implications-for-neuropsychiatric-disorders
#20
Jordi Tomas-Roig, Fabiana Piscitelli, Vanesa Gil, Ester Quintana, Lluís L Ramió-Torrentà, Jose Antonio Del Río, Timothy Patrick Moore, Hope Agbemenyah, Gabriela Salinas, Claudia Pommerenke, Stephan Lorenzen, Tim Beißbarth, Sigrid Hoyer-Fender, Vincenzo Di Marzo, Ursula Havemann-Reinecke
INTRODUCTION: Vulnerability to psychiatric manifestations is achieved by the influence of genetic and environment including stress and cannabis consumption. Here, we used a psychosocial stress model based on resident-intruder confrontations to study the brain corticostriatal-function, since deregulation of corticostriatal circuitries has been reported in many psychiatric disorders. CB1 receptors are widely expressed in the central nervous system and particularly, in both cortex and striatum brain structures...
January 31, 2018: CNS Neuroscience & Therapeutics
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