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https://www.readbyqxmd.com/read/28527758/modulation-of-cb1-cannabinoid-receptor-by-allosteric-ligands-pharmacology-and-therapeutic-opportunities
#1
REVIEW
Leepakshi Khurana, Ken Mackie, Daniele Piomelli, Debra A Kendall
Cannabinoid pharmacology has been intensely studied because of cannabis' pervasive medicinal and non-medicinal uses as well as for the therapeutic potential of cannabinoid-based drugs for the treatment of pain, anxiety, substance abuse, obesity, cancer and neurodegenerative disorders. The identification of allosteric modulators of the cannabinoid receptor 1 (CB1) has given a new direction to the development of cannabinoid-based therapeutics due to the many advantages offered by targeting allosteric site(s)...
May 17, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28527527/small-scale-separation-of-isoxazole-structurally-related-analogues-by-chiral-supercritical-fluid-chromatography
#2
Yasmine Zehani, Lucas Lemaire, Regis Millet, Emmanuelle Lipka
Chromatographic preparative enantioseparation is now the preferred method to obtain milligram amounts of pure enantiomers in the first step of the development of a therapeutic molecule. Supercritical fluid chromatography has many advantages over liquid chromatography and was therefore chosen for the small scale enantioseparation of four original 3-carboxamido-5-aryl isoxazole molecules, ligands of the CB2 cannabinoid receptors. The preparation of about 10mg of each of the eight enantiomers was achieved successfully on a Chiralpak(®) AD-H (tris-3,5-dimethylphenylcarbamate of amylose) polysaccharide based stationary phase with various percentages of ethanol as a co-solvent, through mixed-stream injections and touching-band approach...
May 12, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28526263/n-stearoyl-l-tyrosine-inhibits-the-cell-senescence-and-apoptosis-induced-by-h2o2-in-hek293-tau-cells-via-the-cb2-receptor
#3
Yue Hu, Kai-Yi Zhou, Ze-Jian Wang, Yang Lu, Ming Yin
Although considerable energy and money have been spent trying to inhibit Aβ production and its related metabolic enzyme activities, there are still no drug treatments available to cure even slow for Alzheimer's disease. Therefore, tau protein has been focused recently as the new target for the treatment of Alzheimer's disease. The transfected human embryonic kidney 293 (HEK 293) cells with or without Tau 411 plasmid were used to evaluate the effect of tau protein on cell viability. H2O2 was added to simulate microenvironment of oxidative stress (OS) during aging...
May 16, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28525896/activation-of-cannabinoid-receptor-type-ii-by-am1241-protects-adipose-derived-mesenchymal-stem-cells-from-oxidative-damage-and-enhances-their-therapeutic-efficacy-in-myocardial-infarction-mice-via-stat3-activation
#4
Dong Han, Xiang Li, Wen-Si Fan, Jiang-Wei Chen, Tian-Tian Gou, Tao Su, Miao-Miao Fan, Meng-Qi Xu, Ya-Bin Wang, Sai Ma, Ya Qiu, Feng Cao
The poor survival of cells in ischemic sites diminishes the therapeutic efficacy of stem cell therapy. Previously we and others have reported that Cannabinoid receptor type II (CB2) is protective during heart ischemic injury for its anti-oxidative activity. However, whether CB2 activation could improve the survival and therapeutic efficacy of stem cells in ischemic myocardium and the underlying mechanisms remain elusive. Here, we showed evidence that CB2 agonist AM1241 treatment could improve the functional survival of adipose-derived mesenchymal stem cells (AD-MSCs) in vitro as well as in vivo...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28523112/development-of-highly-affine-and-selective-fluorinated-cannabinoid-type-2-receptor-ligands
#5
Rareş-Petru Moldovan, Kristin Hausmann, Winnie Deuther-Conrad, Peter Brust
Cannabinoid type 2 receptors (CB2 receptors) are involved in various pathological processes, and the visualization of their in vivo availability with positron emission tomography (PET) is of high interest. The study focuses on the introduction of fluorine into the structure of the highly affine and selective CB2 receptor ligand N-(adamantan-1-yl)-5-ethyl-2-methyl-1-phenyl-1H-imidazole-4-carboxamide (5). A novel series of compounds was developed by modifying (i) the adamantane-3-position, (ii) the imidazole-N-phenyl ring, and (iii) the imidazole-2-position, and the impact on the CB2 binding affinity and selectivity toward cannabinoid type 1 receptors (CB1) was evaluated...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28522773/severe-neurological-symptoms-following-synthetic-cannabinoid-intoxication
#6
F van Gorp, L C Wejden, N A Stienstra, E M Kuck, L E M Haas
Synthetic cannabinoids are becoming increasingly popular as substances of abuse. However, in the Netherlands synthetic cannabinoid intoxications are rare. We report a 16-year-old male who became deeply comatose and was admitted to the intensive care unit for invasive mechanical ventilation after a buse of aninitially unknown drug. Routine toxicology screening with an immunoassay only detected tetrahydrocannabinol, but additional tests with liquid chromatography mass spectrometry revealed synthetic cannabinoid use...
May 2017: Netherlands Journal of Medicine
https://www.readbyqxmd.com/read/28520937/atypical-endocannabinoid-signaling-initiates-a-new-form-of-memory-related-plasticity-at-a-cortical-input-to-hippocampus
#7
Weisheng Wang, Yousheng Jia, Danielle T Pham, Linda C Palmer, Kwang-Mook Jung, Conor D Cox, Gavin Rumbaugh, Daniele Piomelli, Christine M Gall, Gary Lynch
Endocannabinoids (ECBs) depress transmitter release at sites throughout the brain. Here, we describe another form of ECB signaling that triggers a novel form of long-term potentiation (LTP) localized to the lateral perforant path (LPP) which conveys semantic information from cortex to hippocampus. Two cannabinoid CB1 receptor (CB1R) signaling cascades were identified in hippocampus. The first is pregnenolone sensitive, targets vesicular protein Munc18-1 and depresses transmitter release; this cascade is engaged by CB1Rs in Schaffer-Commissural afferents to CA1 but not in the LPP, and it does not contribute to LTP...
May 17, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28517235/new-psychoactive-substances-purchasing-and-supply-patterns-in-australia
#8
Rachel Sutherland, Raimondo Bruno, Amy Peacock, Paul Dietze, Courtney Breen, Lucinda Burns, Monica J Barratt
OBJECTIVE: To examine the purchasing and supply patterns of new psychoactive substance (NPS) consumers in Australia. METHOD: Data were obtained from a self-selected sample of 296 past-year NPS consumers, with comparisons made across dimethyltryptamine (n = 104), 2C-x (n = 59), NBOMe (n = 27), and synthetic cannabinoid (n = 22) users. RESULTS: Most consumers (58%) nominated a friend as their main NPS source, and almost half (46%) reported that they had supplied NPS to others in the past year (predominantly "social supply")...
May 18, 2017: Human Psychopharmacology
https://www.readbyqxmd.com/read/28516479/g%C3%AE-s-signalling-of-the-cb1-receptor-and-the-influence-of-receptor-number
#9
David B Finlay, Erin E Cawston, Natasha L Grimsey, Morag R Hunter, Anisha Korde, V Kiran Vemuri, Alexandros Makriyannis, Michelle Glass
BACKGROUND AND PURPOSE: CB1 cannabinoid receptor signalling is canonically mediated through inhibitory Gαi proteins, but signalling through other G proteins occurs under some circumstances; Gαs being the most characterised secondary pathway. Determinants of this signalling switch identified to date include Gαi blockade, CB1 /D2 dopamine receptor co-stimulation, CB1 agonist class, and cell background. The aim of this study was to examine the effects of receptor number and ligand dependence on CB1 signalling...
May 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28516445/role-of-the-endocannabinoid-system-in-vertebrates-emphasis-on-the-zebrafish-model
#10
REVIEW
Francesca Oltrabella, Adam Melgoza, Brian Nguyen, Su Guo
The endocannabinoid system (eCBs), named after the plant Cannabis sativa, comprises cannabinoid receptors, endogenous ligands known as "endocannabinoids", and enzymes involved in the biosynthesis and degradation of these ligands, as well as putative transporters for these ligands. ECBs proteins and small molecules have been detected in early embryonic stages of many vertebrate models. As a result, cannabinoid receptors and endogenous as well as exogenous cannabinoids influence development and behavior in many vertebrate species...
May 17, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/28515817/systematic-review-of-the-potential-role-of-cannabinoids-as-antiproliferative-agents-for-urological-cancers
#11
REVIEW
Shreyas Gandhi, Gaurav Vasisth, Anil Kapoor
INTRODUCTION: The palliative effects of cannabis sativa (marijuana), which include appetite stimulation, attenuation of nausea and emesis, and pain relief, are well known. The active components of cannabis sativa (cannabinoids) and their derivatives have received growing interest due to their diverse pharmacological activities, such as cell growth inhibition and tumour regression. The aim of this review is to look at the current evidence on the antiproliferative effects of cannabinoids in urological malignancies, including renal, prostate, bladder, and testicular cancers...
March 2017: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28515018/plasma-levels-of-the-endocannabinoid-anandamide-related-n-acylethanolamines-and-linoleic-acid-derived-oxylipins-in-patients-with-migraine
#12
Sandra Gouveia-Figueira, Kristina Goldin, Sanaz A Hashemian, Agneta Lindberg, Monica Persson, Malin L Nording, Katarina Laurell, Christopher J Fowler
There is evidence that patients with migraine have deficient levels of the endogenous cannabinoid receptor ligand anandamide (AEA). It is not known, however, if this is a localised or generalised phenomenon. In the present study, levels of AEA, related N-acylethanolamines (NAEs) and linoleic acid-derived oxylipins have been measured in the blood of 26 healthy women and 38 women with migraine (26 with aura, 12 without aura) who were matched for age and body-mass index. Blood samples were taken on two occasions: the first sample near the start of the menstrual cycle (when present) and the second approximately fourteen days later...
May 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28506926/high-times-for-cannabis-epigenetic-imprint-and-its-legacy-on-brain-and-behavior
#13
REVIEW
Henrietta Szutorisz, Yasmin L Hurd
Extensive debates continue regarding marijuana (Cannabis spp), the most commonly used illicit substance in many countries worldwide. There has been an exponential increase of cannabis studies over the past two decades but the drug's long-term effects still lack in-depth scientific data. The epigenome is a critical molecular machinery with the capacity to maintain persistent alterations of gene expression and behaviors induced by cannabinoids that have been observed across the individual's lifespan and even into the subsequent generation...
May 12, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28506704/a-method-to-achieve-extended-cannabis-abstinence-in-cannabis-dependent-patients-with-schizophrenia-and-non-psychiatric-controls
#14
Rachel A Rabin, Karolina Kozak, Konstantine K Zakzanis, Gary Remington, Cristiana Stefan, Alan J Budney, Tony P George
BACKGROUND: Cannabis use disorders (CUD) are common in schizophrenia (~25%) compared to the general population (~3%). Tetrahydrocannabinol (THC), the principal psychoactive component in cannabis is fat-soluble, resulting in an extended period for cannabinoid elimination. While detection of cannabinoids in urine is indicative of prior cannabis exposure, time of last use is difficult to verify sustained abstinence for extended periods (e.g., 28-days) in chronic cannabis users. Therefore, we evaluated the utility of a sustained cannabis abstinence paradigm in patients with schizophrenia and non-psychiatric controls...
May 12, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28503792/synthetic-cannabinoid-use-in-an-acute-psychiatric-inpatient-unit
#15
Richard Vincent Clancy, Robert Charles Hodgson, Arvind Kendurkar, Margarett Ann Terry, Lawrence Dadd, Donna Maria Clancy, Karen Ryan, Maria Hatzistylis, Benjamin Graham Tinman
In the present study, we explored the prevalence of new psychoactive substance use by people admitted into an Australian acute public mental health facility specializing in comorbid mental health and substance use. These substances have since been banned from retail outlets, but the pattern of uptake and reasons people use them is informative in terms of motivations and the management of substance use more generally. A cross-sectional study to explore the use of synthetic cannabis by people admitted to an acute adult mental health unit was undertaken...
May 15, 2017: International Journal of Mental Health Nursing
https://www.readbyqxmd.com/read/28501518/cannabidiol-in-medical-marijuana-research-vistas-and-potential-opportunities
#16
REVIEW
Carola Rong, Yena Lee, Nicole E Carmona, Danielle S Cha, Renee-Marie Ragguett, Joshua D Rosenblat, Rodrigo B Mansur, Roger C Ho, Roger S McIntyre
The high and increasing prevalence of medical marijuana consumption in the general population invites the need for quality evidence regarding its safety and efficacy. Herein, we synthesize extant literature pertaining to the phytocannabinoid cannabidiol (CBD) and its brain effects. The principle phytocannabinoid Δ(9)-tetrahydrocannabinol (Δ(9)-THC) and CBD are the major pharmacologically active cannabinoids. The effect of CBD on brain systems as well as on phenomenological measures (e.g. cognitive function) are distinct and in many cases opposite to that of Δ(9)-THC...
May 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28499834/n-stearoyltyrosine-protects-primary-cortical-neurons-against-oxygen-glucose-deprivation-induced-apoptosis-through-inhibiting-anandamide-inactivation-system
#17
Heng-Jing Cui, Sha Liu, Rui Yang, Guo-Hui Fu, Yang Lu
N-stearoylthrosine (NST), a synthesized anandamide (AEA) analogue, plays a neuroprotective role in neurodegenerative diseases and cerebrovascular diseases. Several studies have demonstrated that the endocannabinoids systems (ECS) are involved in the neuroprotective effects against cerebral ischemic injury. Oxygen-glucose deprivation (OGD)-induced neuronal injury elevated the levels of endocannabinoids and activated ECS. This research was conducted to investigate the neuroprotective effect of NST against OGD-induced neuronal injury in cultured primary cortical neurons and the potential mechanism involved...
May 9, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28497982/neuroprotection-in-oxidative-stress-related-neurodegenerative-diseases-role-of-endocannabinoid-system-modulation
#18
Janos Paloczi, Zoltan V Varga, George Hasko, Pal Pacher
SIGNIFICANCE: Redox imbalance may lead to overproduction of reactive oxygen and nitrogen species (ROS/RNS) and subsequent oxidative tissue damage which is a critical event in the course of neurodegenerative diseases. It is still not fully elucidated, however, whether oxidative stress is the primary trigger or a consequence in process of neurodegeneration. Recent Advances: Increasing evidence suggests that oxidative stress is involved in the propagation of neuronal injury and consequent inflammatory response, which in concert promote development of pathological alterations characteristic of most common neurodegenerative diseases...
May 12, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28496039/pyrolysis-of-ur-144-a-synthetic-cannabinoid-augments-an-affinity-to-human-cb1-receptor-and-cannabimimetic-effects-in-mice
#19
Asuka Kaizaki-Mitsumoto, Kyoko Hataoka, Masahiko Funada, Yuki Odanaka, Hiroki Kumamoto, Satoshi Numazawa
Drug abusers most often smoke 'herbal incense' as a cigarette or inhale it using a smoking tool. Smoking may cause pyrolysis of the drug and produce decomposed products of which biological effect has never been investigated. The synthetic cannabinoid UR-144 is known to undergo thermal degradation, giving a ring-opened isomer, so-called UR-144 degradant. The present study demonstrates by using UR-144 as a model drug that the smoke of burned UR-144 contains the UR-144 degradant. The UR-144 degradant showed approximately four fold higher agonist activity to human CB1 receptor and augmented hypothermic and akinetic actions in mice compared to UR-144...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28495855/marijuana-smoke-induces-severe-pulmonary-hyperresponsiveness-inflammation-and-emphysema-in-a-predictive-mouse-model-not-via-cb1-receptor-activation
#20
Zsuzsanna Helyes, Ágnes Kemény, Kata Csekő, Eva Szoke, Krisztian Elekes, Miklós Mester, Katalin Sándor, Anikó Perkecz, László Kereskai, Laszlo Mark, Ágnes Bona, András Benkő, Erika Pintér, János Szolcsányi, Catherine Ledent, Beáta Sperlágh, Tamás F Molnár
Sporadic clinical reports suggested that marijuana smoking induces spontaneous pneumothorax, but no animal models were available to validate these observations and to study the underlying mechanisms. Therefore, we performed a systematic study in CD1 mice as a predictive animal model and assessed the pathophysiological alterations in response to 4-month-long whole body marijuana smoke with integrative methodologies in comparison with tobacco smoke. Bronchial responsiveness was measured with unrestrained whole body plethysmography, cell profile in the bronchoalveolar lavage fluid with flow-cytometry, myeloperoxidase activity with spectrophotometry, inflammatory cytokines with ELISA, and histopathological alterations by light microscopy...
May 11, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
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