Read by QxMD icon Read


Annelies Cannaert, Jolien Storme, Florian Franz, Volker Auwärter, Christophe P Stove
Synthetic cannabinoids (SCs) are the largest group of compounds currently monitored in Europe by the EU Early Warning System on new psychoactive substances. Emerging recreational use of these products has led to multiple cases of adverse health effects and even death. In contrast to marijuana, where Δ9-tetrahydrocannabinol (Δ9THC) is metabolized to only one major active metabolite, it has been reported that several major phase I metabolites of SCs remain biologically active, exerting cannabinoid (CB) receptor affinity, potency and efficacy greater than Δ9THC...
October 25, 2016: Analytical Chemistry
Xiaojie Liu, Yao Chen, Casey R Vickstrom, Yan Li, Andreu Viader, Benjamin F Cravatt, Qing-Song Liu
The endocannabinoid 2-arachidonoylglycerol (2-AG) mediates retrograde synaptic depression including depolarization-induced suppression of excitation (DSE) and inhibition (DSI). 2-AG is degraded primarily by monoacylglycerol lipase (MAGL), which is expressed in neurons and astrocytes. Using knockout mice in which MAGL is deleted globally or selectively in neurons or astrocytes, we investigated the relative contribution of neuronal and astrocytic MAGL to the termination of DSE and DSI in Purkinje cells (PCs) in cerebellar slices...
October 24, 2016: Scientific Reports
Liting Deng, Wan-Hung Lee, Zhili Xu, Alexandros Makriyannis, Andrea G Hohmann
Neuropathic pain impacts approximately 3-4.5% of the global population and remains an unresolved health problem. The management of neuropathic pain has two distinct goals-prevention of development and control of established neuropathic pain. We examined the impact of both prophylactic and therapeutic treatments with the tricyclic antidepressant desipramine on the development and maintenance of toxic neuropathic pain induced by the chemotherapeutic agent paclitaxel. We also investigated the involvement of endogenous analgesic (i...
October 20, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
A G Sartim, F A Moreira, S R L Joca
CB1 and TRPV1 receptors may have opposite roles in modulating neural activity and, consequently, in regulating the stress response. These receptors are widely expressed in several brain structures, including the ventral medial pre-frontal cortex (vmPFC). The functional consequences of the interaction between CB1 and TRPV1, however, have scarcely been explored. Therefore, we investigated if CB1 and TRPV1 receptors located in the vmPFC would be involved in the behavioral changes induced by the stress of the forced swim test (FST)...
October 19, 2016: Neuroscience
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
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
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
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
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
Xiaolie He, Yanjing Zhu, Mei Wang, Guoxin Jing, Rongrong Zhu, Shilong Wang
Major depression is a complex neuropsychiatric disorder with few treatment approaches. The use of nontargeted antidepressants induced many side effects with their low efficacy. A more precise targeting strategy is to develop nanotechnology-based drug delivery systems; hence, we employed solid lipid nanoparticles (SLNs) to encapsulate HU-211 and curcumin (Cur). The antidepressant effects of the dual-drug nanoparticles (Cur/SLNs-HU-211) for major depression treatment were investigated in corticosterone-induced cellular and animal models of major depression...
2016: International Journal of Nanomedicine
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
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
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
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
Lumír Ondřej Hanuš, Stefan Martin Meyer, Eduardo Muñoz, Orazio Taglialatela-Scafati, Giovanni Appendino
Covering up to January 2016Cannabis sativa L. is a prolific, but not exclusive, producer of a diverse group of isoprenylated resorcinyl polyketides collectively known as phytocannabinoids. The modular nature of the pathways that merge into the phytocannabinoid chemotype translates in differences in the nature of the resorcinyl side-chain and the degree of oligomerization of the isoprenyl residue, making the definition of phytocannabinoid elusive from a structural standpoint. A biogenetic definition is therefore proposed, splitting the phytocannabinoid chemotype into an alkyl- and a β-aralklyl version, and discussing the relationships between phytocannabinoids from different sources (higher plants, liverworts, fungi)...
October 10, 2016: Natural Product Reports
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"