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Akiko Asada, Takahiro Doi, Takaomi Tagami, Akihiro Takeda, Yoshiyuki Sawabe
N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (APINACA) and N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide (APICA) are carboxamide-type synthetic cannabinoids comprising indazole/indole-3-carboxylic acid and adamantan-1-amine moieties. However, in the case of compounds like APINACA or APICA, adamantyl positional isomers exist, wherein either adamantan-1-amine or adamantan-2-amine is present. These adamantyl positional isomers have not been reported in previous studies, and no analytical data are available yet...
October 21, 2016: Drug Testing and Analysis
Qiang Tan, Qianwei Chen, Zhou Feng, Xia Shi, Jun Tang, Yihao Tao, Bing Jiang, Liang Tan, Hua Feng, Gang Zhu, Yunfeng Yang, Zhi Chen
Fibrosis in ventricular system has a role in hydrocephalus following intraventricular hemorrhage (IVH). The cannabinoid receptor 2 (CB2) has been reported to participate in alleviating the fibrosis process of many diseases. However, its role in fibrosis after IVH was unclear so far, and we hypothesized that CB2 activation has potential to attenuate hydrocephalus after IVH via restricting fibrosis. So the present study was designed to investigate this hypothesis in a modified rat IVH model. Autologous non-anticoagulative blood injection model was induced to mimic ventricular extension of hemorrhage in adult Sprague-Dawley rats...
October 18, 2016: Brain Research
Richard J Hamilton, Vadim Keyfes, Sahil S Banka
BACKGROUND: Synthetic cannabinoids (SC) are recreational designer drugs intended to mimic delta-9-tetrahydrocannabinol while surreptitiously circumventing classification by the Drug Enforcement Administration. CASE REPORT: A 50-year-old black male arrived in the Emergency Department transported by Emergency Medical Services (EMS) for altered mental status after complaining of chest pain associated with smoking SCs. EMS found the patient with an empty foil pack labeled "Scooby Snax Limited Edition Blueberry Potpourri...
October 19, 2016: Journal of Emergency Medicine
Massimo Nabissi, Maria Beatrice Morelli, Massimo Offidani, Consuelo Amantini, Silvia Gentili, Alessandra Soriani, Claudio Cardinali, Pietro Leoni, Giorgio Santoni
Several studies showed a potential anti-tumor role for cannabinoids, by modulating cell signaling pathways involved in cancer cell proliferation, chemo-resistance and migration. Cannabidiol (CBD) was previously noted in multiple myeloma (MM), both alone and in synergy with the proteasome inhibitor bortezomib, to induce cell death. In other type of human cancers, the combination of CBD with Δ9-tetrahydrocannabinol (THC) was found to act synergistically with other chemotherapeutic drugs suggesting their use in combination therapy...
October 18, 2016: Oncotarget
Tian Hua, Kiran Vemuri, Mengchen Pu, Lu Qu, Gye Won Han, Yiran Wu, Suwen Zhao, Wenqing Shui, Shanshan Li, Anisha Korde, Robert B Laprairie, Edward L Stahl, Jo-Hao Ho, Nikolai Zvonok, Han Zhou, Irina Kufareva, Beili Wu, Qiang Zhao, Michael A Hanson, Laura M Bohn, Alexandros Makriyannis, Raymond C Stevens, Zhi-Jie Liu
Cannabinoid receptor 1 (CB1) is the principal target of Δ(9)-tetrahydrocannabinol (THC), a psychoactive chemical from Cannabis sativa with a wide range of therapeutic applications and a long history of recreational use. CB1 is activated by endocannabinoids and is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. Here, we present the 2.8 Å crystal structure of human CB1 in complex with AM6538, a stabilizing antagonist, synthesized and characterized for this structural study...
October 20, 2016: Cell
Wei Tuo, Natascha Leleu-Chavain, John Spencer, Supojjanee Sansook, Regis Millet, Philippe Chavatte
Fatty acid ethanolamides (FAEs) and endocannabinoids (ECs) have been shown to alleviate pain and inflammation, regulate motility and appetite, and produce anti-cancer, anxiolytic, and neuroprotective efficacies via cannabinoid receptor type 1 (CB1) or type 2 (CB2), or via peroxisome proliferator-activated receptor α (PPAR-α) stimulation. FAEs and ECs are synthesized by a series of endogenous enzymes, including N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD), diacylglycerol lipase (DAGL), or phospholipase C (PLC), and their metabolism is mediated by several metabolic enzymes, including fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), N-acylethanolamine acid amidase (NAAA), or cyclooxygenase-2 (COX-2)...
October 21, 2016: Journal of Medicinal Chemistry
Wei Bu, Huiling Ren, Yunping Deng, Nobel Del Mar, Natalie M Guley, Bob M Moore, Marcia G Honig, Anton Reiner
We have previously reported that mild TBI created by focal left-side cranial blast in mice produces widespread axonal injury, microglial activation, and a variety of functional deficits. We have also shown that these functional deficits are reduced by targeting microglia through their cannabinoid type-2 (CB2) receptors using 2-week daily administration of the CB2 inverse agonist SMM-189. CB2 inverse agonists stabilize the G-protein coupled CB2 receptor in an inactive conformation, leading to increased phosphorylation and nuclear translocation of the cAMP response element binding protein (CREB), and thus bias activated microglia from a pro-inflammatory M1 to a pro-healing M2 state...
2016: Frontiers in Neuroscience
Thomas J Younts, Hannah R Monday, Barna Dudok, Matthew E Klein, Bryen A Jordan, István Katona, Pablo E Castillo
Long-term changes of neurotransmitter release are critical for proper brain function. However, the molecular mechanisms underlying these changes are poorly understood. While protein synthesis is crucial for the consolidation of postsynaptic plasticity, whether and how protein synthesis regulates presynaptic plasticity in the mature mammalian brain remain unclear. Here, using paired whole-cell recordings in rodent hippocampal slices, we report that presynaptic protein synthesis is required for long-term, but not short-term, plasticity of GABA release from type 1 cannabinoid receptor (CB1)-expressing axons...
October 19, 2016: Neuron
Sivakumar Sanjeev, Deepti Zutshi, Navid Seraji-Bozorgzad, Aashit Shah
Marijuana-based treatment for refractory epilepsy shows promise in surveys, case series and clinical trials. However, literature on their electroencephalography (EEG) effects is sparse. Our objective is to analyze the effect of marijuana on EEG in a 24-year-old patient with idiopathic generalized epilepsy (IGE) treated with cannabis. We blindly reviewed three long-term EEGs-a 24-hour study while only on antiepileptic drugs (AEDs), a 72-hour EEG with Cannabis indica smoked on days one and three in addition to AEDs and a 48-hour EEG with combination C...
October 18, 2016: Journal of Clinical Neurophysiology: Official Publication of the American Electroencephalographic Society
Ning Xia, Huige Li
Under physiological conditions, perivascular adipose tissue (PVAT) attenuates agonist-induced vasoconstriction by releasing vasoactive molecules including hydrogen peroxide, angiotensin 1-7, adiponectin, methyl palmitate, hydrogen sulfide, nitric oxide (NO) and leptin. This anticontractile function of PVAT is lost under conditions of obesity. The central mechanism underlying PVAT dysfunction in obesity is likely to be an "obesity triad" (consisting of PVAT hypoxia, inflammation and oxidative stress) that leads to dysregulation of PVAT-derived vasoregulators...
October 20, 2016: British Journal of Pharmacology
Min Wu, Jinyan Huang, Jianming Zhang, Cyril Benes, Bo Jiao, Ruibao Ren
RAS oncogenic mutations are common in human cancers, but RAS proteins have been difficult to target. We sought to identify pharmacological agents to block the RAS oncogenic signaling by a distinct mechanism. Since the biological activity of RAS proteins rely upon lipid modifications and RAS regulates lipid metabolisms in cancer cells, we screened a bioactive lipid library using a RAS specific cell viability assay. We report the discovery of a new class of inhibitors for RAS transformation. Compounds in the class represented by endocannabinoid N-arachidonoyl dopamine (NADA) can induce cell oncosis, independent of its ability to engage cannabinoid receptors...
October 19, 2016: Molecular Cancer Therapeutics
(no author information available yet)
No abstract text is available yet for this article.
November 2016: Nursing
Mark Haden, John R H Archer, Paul I Dargan, David M Wood
BACKGROUND: MDMB-CHMICA (methyl 2-[[1-(cyclohexylmethyl)indole-3-carbonyl]amino]-3,3-dimethylbutanoate) is a synthetic cannabinoid receptor agonist that has been detected in several recreational drug products in Europe since August 2014. OBJECTIVES: This article aims to describe the prevalence of use, availability, and desired and adverse effects of MDMB-CHMICA. METHODS: Data were collated from published scientific literature, and systematic searches were conducted of publically available Internet sources (the "gray literature"), including websites offering to sell MDMB-CHMICA and Internet discussion forums featuring user reports...
October 19, 2016: Substance Use & Misuse
Rosario Gajardo-Gómez, Valeria C Labra, Carola J Maturana, Kenji F Shoji, Cristian A Santibañez, Juan C Sáez, Christian Giaume, Juan A Orellana
The mechanisms involved in Alzheimer's disease are not completely understood and how astrocytes and their gliotransmission contribute to this neurodegenerative disease remains to be fully elucidated. Previous studies have shown that amyloid-β peptide (Aβ) induces neuronal death by a mechanism that involves the excitotoxic release of ATP and glutamate associated to astroglial hemichannel opening. We have demonstrated that synthetic and endogenous cannabinoids (CBs) reduce the opening of astrocyte Cx43 hemichannels evoked by activated microglia or inflammatory mediators...
October 19, 2016: Glia
Jianfeng Wang, Yunze Xu, Yun Zou, Liangsong Zhu, Baijun Dong, Jiwei Huang, Yonghui Chen, Wei Xue, Yiran Huang, Wen Kong, Jin Zhang
Renal cell carcinoma (RCC) is a common urologic tumor with a poor prognosis. Cannabinoid receptor 1 (CB1), which is a G protein-coupled receptor, has recently been reported to participate in the genesis and development of various cancers. However, the exact role of CB1 in RCC is unknown. The aim of this study was to determine the role of CB1 in RCC cell lines and RCC prognosis, thus underlying its potential as a therapeutic target. Immunohistochemistry and western blots were performed to investigate the expression of CB1 in RCC tissues and to determine its clinicopathological significance in RCC patients...
October 18, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Sanjay Bhandari, Thangam Venkatesan
Cyclic vomiting syndrome (CVS) is a chronic functional gastrointestinal disorder that is characterized by episodic nausea and vomiting. Initially thought to only affect children, CVS in adults was often misdiagnosed with significant delays in therapy. Over the last decade, there has been a considerable increase in recognition of CVS in adults but there continues to be a lack of knowledge about management of this disorder. This paper seeks to provide best practices in the treatment of CVS and also highlight some novel therapies that have the potential in better treating this disorder in the future...
October 18, 2016: Current Treatment Options in Gastroenterology
Oscar Prospéro-García, Octavio Amancio-Belmont, Alline L Becerril Meléndez, Alejandra E Ruiz-Contreras, Mónica Méndez-Díaz
Sleep is regulated by several brain structures, neurotransmitters and neuromodulators. Endocannabinoids (eCBs) are a group of lipids with modulatory activity in the brain and bind mainly to cannabinoid receptors CB1R and CB2R, thereby modulating several brain functions, (memory, mood, food intake, pain perception). Oleoylethanolamide and palmitoylethanolamide belong to the N-acylethanolamides (NAEs) family, another type of active endogenous lipids. They bind to the peroxisome proliferator-activated receptor α but not to CB1R, thereby modulating food satiety, inflammation and pain...
October 15, 2016: Neuroscience and Biobehavioral Reviews
Jenny L Wiley, Julie A Marusich, Brian F Thomas
Originally developed as research tools for use in structure-activity relationship studies, synthetic cannabinoids contributed to significant scientific advances in the cannabinoid field. Unfortunately, a subset of these compounds was diverted for recreational use beginning in the early 2000s. As these compounds were banned, they were replaced with additional synthetic cannabinoids with increasingly diverse chemical structures. This chapter focuses on integration of recent results with those covered in previous reviews...
October 18, 2016: Current Topics in Behavioral Neurosciences
Torbjörn U C Järbe, Jimit Girish Raghav
The phenomenon of consuming synthetic cannabinoids ("Spice") for recreational purposes is a fairly recent trend. However, consumption of cannabis dates back millennia, with numerous accounts written on the experience of its consumption, and thousands of scientific reports published on the effects of its constituents in laboratory animals and humans. Here, we focus on consolidating the scientific literature on the effects of "Spice" compounds in various behavioral assays, including assessing abuse liability, tolerance, dependence, withdrawal, and potential toxicity...
October 18, 2016: Current Topics in Behavioral Neurosciences
Yun Ling, Zhuang-Li Hu, Qing-Li Meng, Peng Fang, Hai-Xia Liu
Our previous study found that some trigeminal ganglion (TG) nerve endings in the inner walls of rat anterior chambers were mechanosensitive, and transient receptor potential ankyrin 1 (TRPA1) was an essential mechanosensitive channel in the membrane. To address the effect of cannabinoids on the mechanosensitive TG nerve endings in the inner walls of anterior chambers of rat eye, we investigated the effect of the (R)-(+)-WIN55, 212-2 mesylate salt (WIN), a synthetic cannabinoid on their cell bodies in vitro...
October 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
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