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https://www.readbyqxmd.com/read/28445587/cb1-receptors-downregulate-a-camp-epac2-plc-pathway-to-silence-the-nerve-terminals-of-cerebellar-granule-cells
#1
Beatris Alonso, David Bartolomé-Martín, José Javier Ferrero, Jorge Ramírez-Franco, Magdalena Torres, José Sánchez-Prieto
Cannabinoid receptors mediate short-term retrograde inhibition of neurotransmitter release, as well as long-term depression of synaptic transmission at excitatory synapses. The responses of individual nerve terminals in VGLUT1-pHluorin transfected cerebellar granule cells to cannabinoids have shown that prolonged activation of cannabinoid type 1 receptors (CB1Rs) silences a subpopulation of previously active synaptic boutons. Adopting a combined pharmacological and genetic approach to study the molecular mechanisms of CB1R-induced silencing, we found that adenylyl cyclase inhibition decreases cAMP levels while it increases the number of silent synaptic boutons and occludes the induction of further silencing by the cannabinoid agonist HU-210...
April 26, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28445405/significant-tic-reduction-in-an-otherwise-treatment-resistant-patient-with-gilles-de-la-tourette-syndrome-following-treatment-with-nabiximols
#2
Ahmad Seif Kanaan, Ewgeni Jakubovski, Kirsten Müller-Vahl
Early anecdotal reports and preliminary studies suggested that cannabinoid-based medicines such as delta-9-tetrahydrocannabinol (THC) are effective in the treatment of Gilles de la Tourette syndrome (TS). We report a single case study of a patient with otherwise treatment-resistant TS successfully treated with nabiximols. Our patient was a 22-year-old male suffering from severe and complex TS. Treatment with nabiximols was commenced at a dose of 1 puff/day (= 100 μL containing 2.7 mg THC and 2.5 mg cannabidiol (CBD)) and slowly increased up to a dosage of 3 × 3 puffs/day (= 24...
April 26, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28444659/new-psychoactive-substances-nps-a-challenge-for-the-addiction-treatment-services
#3
Norbert Scherbaum, F Schifano, Udo Bonnet
Over the last few years, hundreds of new psychoactive substances (NPS) have been identified in Europe. Apart from some herbal compounds, NPS mainly include synthetic cannabinoids and a range of new synthetic stimulants (e. g., cathinones). Synthetic NPS are often developed whilst modifying the basic chemical (e. g., phenethylamine or tryptamine) structure. Although the pharmacology and toxicology of most NPS are hardly known, they are being offered, especially online, as "bath salts," as "incense mixtures," or under other misleading labels...
April 25, 2017: Pharmacopsychiatry
https://www.readbyqxmd.com/read/28442584/apparent-cb1-receptor-rimonabant-affinity-estimates-combination-with-thc-and-synthetic-cannabinoids-in-the-mouse-in-vivo-triad-model
#4
Travis W Grim, Anthony J Morales, Brian F Thomas, Jenny L Wiley, Gregory W Endres, Sidney S Negus, Aron H Lichtman
Synthetic cannabinoids (SCs) represent an emerging class of abused drugs associated with psychiatric complications and other substantial health risks. These ligands are largely sold over the internet for human consumption presumably because of their high cannabinoid 1 receptor (CB1R) affinity and potency in eliciting similar pharmacological effects as Δ9-tetrahydrocannabinol (THC), while circumventing laws illegalizing this plant. Factors potentially contributing to the increased prevalence of SC abuse and related hospitalizations, such as increased CB1R efficacy and non-CB1R targets, highlight the need for quantitative pharmacological analyses to determine receptor mediation of the pharmacological effects of cannabinoids...
April 25, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28442324/the-interactive-role-of-cb1-receptors-and-l-type-calcium-channels-in-hippocampal-long-term-potentiation-in-rats
#5
Hamidreza Komaki, Fargol Saadat, Siamak Shahidi, Abdolrahman Sarihi, Parisa Hasanein, Alireza Komaki
'Long-term potentiation (LTP) of synaptic responses is a widely researched model of synaptic plasticity that occurs during learning and memory. The cannabinoid system is an endogenous system that modulate this kind of synaptic plasticity. In addition, voltage dependent calcium channels is essential for induction of LTP at some synapses in the hippocampus. However, there is currently debate over the interaction between L-type calcium channels and cannabinoid system on the synaptic plasticity. In this study, we examined the effects of an acute administration of the cannabinoid antagonist AM251 following a chronic administration of the Ca(2+) channel blocker verapamil on LTP induction in the hippocampal dentate gyrus(DG) of rats...
April 22, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28441341/a-long-term-treatment-with-arachidonyl-2-chloroethylamide-combined-with-valproate-increases-neurogenesis-in-a-mouse-pilocarpine-model-of-epilepsy
#6
Marta Andres-Mach, Mirosław Zagaja, Agnieszka Haratym-Maj, Radosław Rola, Maciej Maj, Joanna Haratym, Monika Dudra-Jastrzębska, Jarogniew J Łuszczki
Rational polytherapy in the treatment of refractory epilepsy has been the main therapeutic modality for several years. In treatment with two or more antiepileptic drugs (AEDs), it is of particular importance that AEDs be selected based on their high anticonvulsant properties, minimal side effects, and impact on the formation of new neurons. The aim of the study was to conduct an in vivo evaluation of the relationship between treatments with synthetic cannabinoid arachidonyl-2'-chloroethylamide (ACEA) alone or in combination with valproic acid (VPA) and hippocampal neurogenesis in a mouse pilocarpine model of epilepsy...
April 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28441106/jwh-122-consumption-adverse-effects-a-case-of-hallucinogen-persisting-perception-disorder-five-year-follow-up
#7
Maurizio Coppola, Raffaella Mondola
Synthetic cannabinoid receptor agonists are a heterogeneous group of psychotropic drugs functionally related to Δ9-tetrahydrocannabinol. These substances, marketed as cannabis substitutes, have been associated with numerous cases of severe intoxication and death across the world. In our article, we describe a case of hallucinogen persisting perception disorder developing in a natural cannabis user after consumption of JWH-122, a naphthoylindole largely used since 2010. Clinical symptomatology persisted for about four years and was alleviated through treatment with clonazepam...
April 25, 2017: Journal of Psychoactive Drugs
https://www.readbyqxmd.com/read/28440729/2-arachidonoylglycerol-endocannabinoid-signaling-coupled-to-metabotropic-glutamate-receptor-type-5-modulates-anxiety-like-behavior-in-the-rat-ventromedial-prefrontal-cortex
#8
Ana F Almeida-Santos, Fabricio A Moreira, Francisco S Guimaraes, Daniele C Aguiar
2-Arachidonoylglycerol and anandamide are the main endocannabinoids, which act through cannabinoid type-1 and type-2 receptors. Among its many functions, anandamide modulates anxiety-like behaviors in the ventromedial prefrontal cortex. The role of 2-arachidonoylglycerol in this region, however, has remained unclear. Here, we verified whether intra- ventromedial prefrontal cortex injection of 2-arachidonoylglycerol or URB602, a monoacylglycerol lipase inhibitor (responsible for 2-arachidonoylglycerol hydrolysis), induce anxiolytic-like effects in Wistar rats...
April 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28440188/trp-channels-as-novel-targets-for-endogenous-ligands-focus-on-endocannabinoids-and-nociceptive-signalling
#9
Maksim V Storozhuk, Alexander V Zholos
The endocannabinoid system is gaining steadily increasing research interest as its important role in the regulation of many fundamental physiological processes becomes more and more evident. One area which received particularly significant attention concerns targeting the endocannabinoid system as a useful strategy in pain control, especially in refractory, difficult to treat cases of chronic pain. Apart from the classical targets of cannabinoids, the CB1 and CB2 receptors, several members of the large TRP family of Ca2+-permeable cation channels have been designated as "ionotropic cannabinoid receptors" to highlight their role in cannabinoid signalling...
April 24, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28439004/endocannabinoid-system-acts-as-a-regulator-of-immune-homeostasis-in-the-gut
#10
Nandini Acharya, Sasi Penukonda, Tatiana Shcheglova, Adam T Hagymasi, Sreyashi Basu, Pramod K Srivastava
Endogenous cannabinoids (endocannabinoids) are small molecules biosynthesized from membrane glycerophospholipid. Anandamide (AEA) is an endogenous intestinal cannabinoid that controls appetite and energy balance by engagement of the enteric nervous system through cannabinoid receptors. Here, we uncover a role for AEA and its receptor, cannabinoid receptor 2 (CB2), in the regulation of immune tolerance in the gut and the pancreas. This work demonstrates a major immunological role for an endocannabinoid. The pungent molecule capsaicin (CP) has a similar effect as AEA; however, CP acts by engagement of the vanilloid receptor TRPV1, causing local production of AEA, which acts through CB2...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438833/g-protein-gi1-exhibits-basal-coupling-but-not-preassembly-with-g-protein-coupled-receptors
#11
Alexey Bondar, Josef Lazar
The Gi/o protein family transduces signals from a diverse group of G protein-coupled receptors (GPCRs). The observed specificity of Gi/o-GPCR coupling and high rate of Gi/o signal transduction have been hypothesized to be enabled by existence of stable associates between Gi/o proteins and their cognate GPCRs in the inactive state (Gi/o-GPCR preassembly). To test this hypothesis, we applied the recently developed technique of two-photon polarization microscopy (2PPM) to Gαi1 subunits labeled with fluorescent proteins and four GPCRs (the α2A-adrenergic receptor (α2A-AR), γ-aminobutyric acid receptor B (GABAB), cannabinoid receptor type 1 (CB1R) and dopamine receptor type 2 (D2R))...
April 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28438413/functional-redundancy-between-canonical-endocannabinoid-signaling-systems-in-the-modulation-of-anxiety
#12
Gaurav Bedse, Nolan D Hartley, Emily Neale, Andrew D Gaulden, Toni A Patrick, Philip J Kingsley, Md Jashim Uddin, Niels Plath, Lawrence J Marnett, Sachin Patel
BACKGROUND: Increasing the available repertoire of effective treatments for mood and anxiety disorders represents a critical unmet need. Pharmacological augmentation of endogenous cannabinoid (eCB) signaling has been suggested to represent a novel approach to the treatment of anxiety disorders; however, the functional interactions between two canonical eCB pathways mediated via anandamide (N-arachidonylethanolamine [AEA]) and 2-arachidonoylglycerol (2-AG) in the regulation of anxiety are not well understood...
March 15, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28437860/chronic-inhibition-of-fatty-acid-amide-hydrolase-by-urb597-produces-differential-effects-on-cardiac-performance-in-normotensive-and-hypertensive-rats
#13
Anna Pedzinska-Betiuk, Jolanta Weresa, Marek Toczek, Marta Baranowska-Kuczko, Irena Kasacka, Ewa Harasim-Symbor, Barbara Malinowska
BACKGROUND AND PURPOSE: Fatty acid amide hydrolase (FAAH) inhibitors are postulated to possess anti-hypertensive potential, because their acute injection decreases blood pressure (BP) in spontaneously hypertensive rats (SHR) partially through normalization of cardiac contractile function. Here, we examined whether the potential hypotensive effect of chronic FAAH inhibition by URB597 in hypertensive rats correlates with changes in cardiac performance. EXPERIMENTAL APPROACH: Experiments were performed using perfused hearts and left atria isolated from 8-10 week old SHR, age-matched deoxycorticosterone acetate (DOCA-salt) rats and normotensive controls chronically treated with URB597 (1 mg kg(-1) ) or vehicle...
April 24, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28434588/the-endocannabinoid-system-as-a-target-for-novel-anxiolytic-drugs
#14
REVIEW
Sachin Patel, Mathew N Hill, Joseph F Cheer, Carsten T Wotjak, Andrew Holmes
The endocannabinoid (eCB) system has attracted attention for its role in various behavioral and brain functions, and as a therapeutic target in neuropsychiatric disease states, including anxiety disorders and other conditions resulting from dysfunctional responses to stress. In this mini-review, we highlight components of the eCB system that offer potential 'druggable' targets for new anxiolytic medications, emphasizing some of the less well-discussed options. We discuss how selectively amplifying eCBs recruitment by interfering with eCB-degradation, via fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), has been linked to reductions in anxiety-like behaviors in rodents and variation in human anxiety symptoms...
May 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28434182/recent-trends-in-alcohol-and-other-drug-use-among-police-detainees-in-new-zealand-2010-2015
#15
Chris Wilkins, Jitesh Prasad, Karl Parker, Marta Rychert, Helen Moewaka Barnes
BACKGROUND: New Zealand has unusual patterns of recreational substance use by international standards including low levels of cocaine and heroin use, and high methamphetamine use. AIMS: This paper examines recent trends in alcohol and other drug use among police detainees in New Zealand over the past six years. METHOD: The paper utilises data from the New Zealand Arrestee Drug Use Monitoring (NZ-ADUM) study. NZ-ADUM interviewed approximately 800 police detainees each year at four central city police watch houses (i...
April 23, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28433979/lethal-high-acute-disseminated-encephalomyelitis-adem-triggered-by-toxic-effect-of-synthetic-cannabinoid-black-mamba
#16
Kiran Samra, Ian S Boon, Gregory Packer, Saiju Jacob
A previously well 25-year-old man presented with agitation, double incontinence and left-sided incoordination. His symptoms started after smoking a synthetic cannabinoid (black mamba) 5 days earlier. Over 48 hours, he developed aphasia, generalised hypertonia, hyper-reflexia and dense left hemiparesis. This progressed to profuse diaphoresis, fever, tachycardia, hypertension and a possible seizure necessitating admission to the intensive care unit. CT head and cerebrospinal fluid analysis were unremarkable...
April 22, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28433118/the-role-of-public-health-in-combatting-synthetic-cannabinoid-use-in-adolescents
#17
Katherine E Warren, Shirli Tay, Leana S Wen
As the country struggles to address an epidemic of alcohol and drug overdose, a wide-ranging category of chemical substances known as synthetic drugs have provoked a new sense of public urgency over the past decade. Synthetic cannabinoids, a heterogeneous and evolving set of synthetic compounds that act on endogenous cannabinoid receptors, have become particularly popular among adolescents due to their relative ease of access and reputation as a "legal high." The Baltimore City Health Department has worked to combat the recent surge in synthetic drug use through a major public awareness campaign, legislative reform, and retailer engagement and compliance initiative...
May 2017: Journal of Adolescent Health: Official Publication of the Society for Adolescent Medicine
https://www.readbyqxmd.com/read/28431968/cannabinoid-cb1-and-cb2-receptors-differentially-modulate-l-and-t-type-ca-2-channels-in-rat-retinal-ganglion-cells
#18
Wen-Jing Qian, Ning Yin, Feng Gao, Yanying Miao, Qian Li, Fang Li, Xing-Huai Sun, Xiong-Li Yang, Zhongfeng Wang
Endocannabinoid signaling system is involved in regulating multiple neuronal functions in the central nervous system by activating G-protein coupled cannabinoid CB1 and CB2 receptors (CB1Rs and CB2Rs). Growing evidence has shown that CB1Rs and CB2Rs are extensively expressed in retinal ganglion cells (RGCs). Here, modulation of L- and T-types Ca(2+) channels by activating CB1Rs and CB2Rs in RGCs was investigated. Triple immunofluorescent staining showed that L-type subunit CaV1.2 was co-localized with T-type subunits (CaV3...
April 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28428743/editorial-the-cb2-cannabinoid-system-a-new-strategy-in-neurodegenerative-disorder-and-neuroinflammation
#19
EDITORIAL
Marialessandra Contino, Elena Capparelli, Nicola A Colabufo, Ashley I Bush
No abstract text is available yet for this article.
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28428628/inflammatory-and-neuropathic-nociception-is-preserved-in-gpr55-knockout-mice
#20
Lawrence M Carey, Tannia Gutierrez, Liting Deng, Wan-Hung Lee, Ken Mackie, Andrea G Hohmann
The G-protein coupled receptor GPR55 has been postulated to serve as a novel cannabinoid receptor. A previous report indicated that GPR55 knockout mice fail to develop mechanical hyperalgesia, suggesting a pro-nociceptive role for GPR55 in the control of nociceptive responding. However, GPR55 knockout mice remain incompletely characterized in models of pathological pain. Here we provide a comprehensive assessment of responses of GPR55 knockout and wild-type mice to mechanical and thermal (heat, cold) stimulation in multiple, mechanistically distinct models of inflammatory and neuropathic pain...
April 20, 2017: Scientific Reports
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