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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
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
Kari A Johnson, David M Lovinger
In this issue of Neuron, Younts et al. (2016) demonstrate that activation of presynaptic CB1 receptors by retrograde endocannabinoid signaling stimulates protein synthesis in axon terminals to induce long-term depression of hippocampal inhibitory transmission.
October 19, 2016: Neuron
Gabriella Juhasz, Eva Csepany, Mate Magyar, Andrea Edit Edes, Nora Eszlari, Gabor Hullam, Peter Antal, Gyongyi Kokonyei, Ian Muir Anderson, John Francis William Deakin, Gyorgy Bagdy
One of the main effects of the endocannabinoid system in the brain is stress adaptation with presynaptic endocannabinoid receptor 1 (CB1 receptors) playing a major role. In the present study, we investigated whether the effect of the CB1 receptor coding CNR1 gene on migraine and its symptoms is conditional on life stress. In a cross-sectional European population (n = 2426), recruited from Manchester and Budapest, we used the ID-Migraine questionnaire for migraine screening, the Life Threatening Experiences questionnaire to measure recent negative life events (RLE), and covered the CNR1 gene with 11 SNPs...
October 19, 2016: Genes, Brain, and Behavior
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
Aziz Homayouni Rad, Farnaz Sahhaf, Tohid Hassanalilou, Hanieh-Sadat Ejtahed, Negar Motayagheni, Ahmad-Reza Soroush, Mina Javadi, Amir Mohammad Mortazavian, Leila Khalili
BACKGROUND: Diabetes mellitus, a condition of multifactorial origin, is related to the intestinal microbiota by numerous molecular mechanisms. Controlling the vast increase in the prevalence of diabetes needs a natural and safe solution. Probiotics, known as live microorganisms that exert health benefits to the host, have anti-diabetic property. OBJECTIVE: This review will highlight the current evidences in probiotic effectiveness and future prospects for exploring probiotic therapy in the prevention and control of diabetes...
October 14, 2016: Current Diabetes Reviews
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
Giorgia Macedonio, Azzurra Stefanucci, Cristina Maccallini, Sako Mirzaie, Ettore Novellino, Adriano Mollica
The endocannabinoid system is activated by the binding of natural arachidonic acid derivatives (endogenous cannabinoids or endocannabinoids) as lipophilic messengers to cannabinoid receptors CB1 and CB2. The endocannabinoid system comprises also many hydrolytic enzymes responsible for the endocannabinoids cleavage, such as FAAH and MAGL. These two enzymes are possible therapeutic targets for the development of new drugs as indirect cannabinoid agonists. Recently a new family of endocannabinoid modulators was discovered; the lead of this family is the nonapeptide hemopressin produced from enzymatic cleavage of the α-chain of hemoglobin and acting as negative allosteric modulator of CB1...
October 7, 2016: Protein and Peptide Letters
Stephen Sidney
Marijuana is used by millions of people, with use likely to increase in the USA because of the trend towards increased decriminalization and legalization. Obesity and diabetes mellitus (DM) rates have increased dramatically in the USA over the past 30 years, with a recent estimate of 29 million individuals with DM. Because there is a plausible link between marijuana use and diabetes due to the known effects of cannabinoids on adipose tissue and glucose/insulin metabolism, it is important to study and understand how marijuana use is related to obesity and diabetes...
November 2016: Current Diabetes Reports
Eric Murillo-Rodríguez, Sergio Machado, Nuno Barbosa Rocha, Henning Budde, Ti-Fei Yuan, Oscar Arias-Carrión
The endocannabinoid system comprises receptors (CB1 and CB2 cannabinoid receptors), enzymes (Fatty Acid Amide Hydrolase [FAAH], which synthesizes the endocannabinoid anandamide), as well as the anandamide membrane transporter (AMT). Importantly, previous experiments have demonstrated that the endocannabinoid system modulates multiple neurobiological functions, including sleep. For instance, SR141716A (the CB1 cannabinoid receptor antagonist) as well as URB597 (the FAAH inhibitor) increase waking in rats whereas VDM-11 (the blocker of the AMT) enhances sleep in rodents...
October 13, 2016: Neuroscience
Luara A Batista, Andrea S Haibara, Luiz C Schenberg, Fabricio A Moreira
Selective stimulation of carotid chemoreceptors by intravenous infusion of low doses of potassium cyanide (KCN) produces short-lasting escape responses that have been proposed as a model of panic attack. In turn, preclinical studies suggest that facilitation of the endocannabinoid system attenuate panic-like responses. Here, we compared the effects of cannabinoid-related compounds to those of alprazolam, a clinically effective panicolytic, on the duration of the escape reaction induced by intravenous infusion of KCN (80μg) in rats...
October 11, 2016: Behavioural Brain Research
Ermelinda Lomazzo, Florian König, Leila Abassi, Ruth Jelinek, Beat Lutz
Persistent stress triggers a variety of mechanisms, which may ultimately lead to the occurrence of anxiety- and depression-related disorders. Epigenetic modifications represent a mechanism by which chronic stress mediates long-term effects. Here, we analyzed brain tissue from mice exposed to chronic unpredictable stress (CUS), which induced impaired emotional and nociceptive behaviors. As endocannabinoid (eCB) and neuropeptide-Y (Npy) systems modulate emotional processes, we hypothesized that CUS may affect these systems through epigenetic mechanisms...
October 10, 2016: Neuropharmacology
Simonnet A, Zamberletti E, Cador M, Rubino T, Caillé S
The role of the endocannabinoid system in nicotine addiction is being increasingly acknowledged. Acute inhibition of anandamide (AEA) degradation efficiently reduces nicotine withdrawal-induced affective symptoms in rats and fatty acid amide hydrolase (FAAH), the degradation enzyme of AEA, has been proposed as a possible treatment against nicotine addiction. However, it is unclear whether chronic inhibition of AEA during nicotine abstinence will have beneficial or deleterious affective side-effects. Using a rat model of nicotine addiction, we found that, during abstinence, rats injected daily with a FAAH inhibitor (URB597) developed a depressive-like phenotype...
October 10, 2016: Neuropharmacology
Rocio Saravia, África Flores, Ainhoa Plaza-Zabala, Arnau Busquets-Garcia, Antoni Pastor, Rafael de la Torre, Vincenzo Di Marzo, Giovanni Marsicano, Andrés Ozaita, Rafael Maldonado, Fernando Berrendero
BACKGROUND: Tobacco withdrawal is associated with deficits in cognitive function, including attention, working memory, and episodic memory. Understanding the neurobiological mechanisms involved in these effects is crucial because cognitive deficits during nicotine withdrawal may predict relapse in humans. METHODS: We investigated in mice the role of CB1 cannabinoid receptors (CB1Rs) in memory impairment and spine density changes induced by nicotine withdrawal precipitated by the nicotinic antagonist mecamylamine...
July 16, 2016: Biological Psychiatry
Mikuláš Pura, Peter Vaňuga
Recent studies suggest an important role for the skeletal endocannabinoid system in the regulation of bone mass in both physiological and pathological conditions. Both major endocannabinoids (anandamid and 2-arachidonoylglycerol), endocannabinoid receptors - CB1-receptor (CB1R) a CB2-receptor (CB2R) and the endocannabinoid metabolizing enzymes are present or expressed in osteoblasts and osteoclasts. Previous studies identified multiple risk and protective variants of CNR2 gene dealing with the relationship to bone density and/or osteoporosis...
2016: Vnitr̆ní Lékar̆ství
Manuel Luis Wolfson, Julieta Aisemberg, Fernando Correa, Ana María Franchi
BACKGROUND AND PURPOSE: Maternal infections with Gram-negative bacteria are associated with miscarriage and are one of the most common complications during pregnancy. Previous studies from our group have shown that lipopolysaccharide (LPS)-activated infiltrating peripheral blood mononuclear cells (PBMC) into decidual tissue play an important role on the establishment of a local inflammatory process that result in embryo cytotoxicity and early embryo resorption. Moreover, we have also shown that an increased endocannabinoid tone mediates LPS-induced deleterious effects during early pregnancy loss...
October 12, 2016: Journal of Cellular Physiology
E Carlino, A Piedimonte, F Benedetti
Placebos have long been considered a nuisance in clinical research, for they have always been used as comparators for the validation of new treatments. By contrast, today they represent an active field of research, and, due to the involvement of many mechanisms, the study of the placebo effect can actually be viewed as a melting pot of concepts and ideas for neuroscience. There is not a single placebo effect, but many, with different mechanisms across different medical conditions and therapeutic interventions...
2017: Handbook of Clinical Neurology
Katalin Solymosi, Attila Köfalvi
Cannabis is one of the earliest cultivated plants. Cannabis of industrial utility and culinary value is generally termed as hemp. Conversely, cannabis that is bred for medical, spiritual and recreational purposes is called marijuana. The female marijuana plant produces a significant quantity of bio- and psychoactive phytocannabinoids, which regained the spotlight with the discovery of the endocannabinoid system of the animals in the early 90's. Nevertheless, marijuana is surrounded by controversies, debates and misconceptions related to its taxonomic classification, forensic identification, medical potential, legalization and its long-term health consequences...
October 4, 2016: Mini Reviews in Medicinal Chemistry
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