Potential Anxiogenic Effects of Cannabinoid CB1
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ARTICLE https://doi.org/10.1038/s41467-020-19780-z OPEN Endocannabinoid signaling regulates the reinforcing and psychostimulant effects of ketamine in mice Wei Xu1,3, Hongchun Li1,3, Liang Wang1, Jiamei Zhang1, Chunqi Liu1, Xuemei Wan1, Xiaochong Liu1, Yiming Hu1, ✉ Qiyao Fang1, Yuanyuan Xiao1, Qian Bu1, Hongbo Wang2, Jingwei Tian2, Yinglan Zhao1 & Xiaobo Cen 1 The abuse potential of ketamine limits its clinical application, but the precise mechanism remains largely unclear. Here we discovered that ketamine significantly remodels the 1234567890():,; endocannabinoid-related lipidome and activates 2-arachidonoylglycerol (2-AG) signaling in the dorsal striatum (caudate nucleus and putamen, CPu) of mice. Elevated 2-AG in the CPu is essential for the psychostimulant and reinforcing effects of ketamine, whereas blockade of the cannabinoid CB1 receptor, a predominant 2-AG receptor, attenuates ketamine-induced remodeling of neuronal dendrite structure and neurobehaviors. Ketamine represses the transcription of the monoacylglycerol lipase (MAGL) gene by promoting the expression of PRDM5, a negative transcription factor of the MAGL gene, leading to increased 2-AG pro- duction. Genetic overexpression of MAGL or silencing of PRDM5 expression in the CPu robustly reduces 2-AG production and ketamine effects. Collectively, endocannabinoid signaling plays a critical role in mediating the psychostimulant and reinforcing properties of ketamine. 1 National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, 610041 Chengdu, People’s Republic of China. 2 Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, 264005 Yantai, People’s Republic of China. -
British Journal of Nutrition (2009), 101, 457–464 Doi:10.1017/S0007114508024008 Q the Authors 2008
Downloaded from https://www.cambridge.org/core British Journal of Nutrition (2009), 101, 457–464 doi:10.1017/S0007114508024008 q The Authors 2008 Administration of a dietary supplement (N-oleyl-phosphatidylethanolamine . IP address: and epigallocatechin-3-gallate formula) enhances compliance with diet in healthy overweight subjects: a randomized controlled trial 170.106.35.93 Mariangela Rondanelli1,2*, Annalisa Opizzi1,2, Sebastiano Bruno Solerte3, Rosita Trotti4, Catherine Klersy5 6 , on and Roberta Cazzola 29 Sep 2021 at 01:44:33 1Section of Human Nutrition and Dietetics, Department of Applied Health Sciences, Faculty of Medicine, University of Pavia, Pavia, Italy 2Endocrinology and Nutrition Unit, ASP, II.AA.RR, University of Pavia, ‘Istituto Santa Margherita’, Pavia, Italy 3Department of Internal Medicine, Geriatrics and Gerontologic Clinic, University of Pavia, ‘Istituto Santa Margherita’, Pavia, Italy 4Laboratory of Biochemical Chemistry, Neurological Institute ‘C. Mondino’, IRCCS, Pavia, Italy , subject to the Cambridge Core terms of use, available at 5Service of Biometry and Clinical Epidemiology, Fondazione IRCCS ‘Policlinico San Matteo’, Pavia, Italy 6Department of Preclinical Sciences ‘LITA Vialba’, Faculty of Medicine, University of Milan, Milan, Italy (Received 21 February 2008 – Revised 29 April 2008 – Accepted 20 May 2008 – First published online 1 July 2008) Many studies have found that N-oleyl-ethanolamine (NOE), a metabolite of N-oleyl-phosphatidylethanolamine (NOPE), and epigallocatechin-3- gallate (EGCG) inhibit food intake. The main aim of this study was to evaluate the efficacy of 2 months of administration of an oily NOPE– EGCG complex (85 mg NOPE and 50 mg EGCG per capsule) and its effect on compliance with diet in healthy, overweight people. -
Bioactivation Pathways of the Cb1r Antagonist Rimonabant
DMD Fast Forward. Published on July 6, 2011 as DOI: 10.1124/dmd.111.039412 DMDThis Fast article Forward. has not been Published copyedited and on formatted. July 6, The2011 final as version doi:10.1124/dmd.111.039412 may differ from this version. DMD #39412 Bioactivation Pathways of the CB1r Antagonist Rimonabant Downloaded from Moa Andresen Bergström, Emre M. Isin, Neal Castagnoli Jr., and Claire E. Milne dmd.aspetjournals.org CVGI iMED DMPK, AstraZeneca R&D Mölndal, Sweden (M.A.B., E.M.I., C.E.M.); Department of Chemistry, Virginia Tech, and Virginia College of Osteopathic Medicine, Blacksburg, VA 24061 (N.C.) at ASPET Journals on October 1, 2021 1 Copyright 2011 by the American Society for Pharmacology and Experimental Therapeutics. DMD Fast Forward. Published on July 6, 2011 as DOI: 10.1124/dmd.111.039412 This article has not been copyedited and formatted. The final version may differ from this version. DMD #39412 Running Title: Bioactivation Pathways of the CB1r Antagonist Rimonabant Corresponding Author: Dr. Moa Andresen Bergström, CVGI iMED DMPK, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden. Tel.: +46317762551, Fax.: +46317763760, E-mail: [email protected]. Number of Text Pages: 18 Downloaded from Number of Tables: 2 Number of Figures: 6 dmd.aspetjournals.org Number of Schemes: 3 Number of References: 40 Number of Words in Abstract: 227 at ASPET Journals on October 1, 2021 Number of Words in Introduction: 604 Number of Words in Discussion: 1500 List of Nonstandard Abbreviations: ADRs, adverse drug reactions; BFC, 7-benzyloxy-4- trifluoromethylcoumarin; CYP, cytochrome P450; HFC, 7-hydroxy-4- (trifluoromethyl)coumarin; HLMs, human liver microsomes; IADRs, idiosyncratic adverse drug reactions; KCN, potassium cyanide; LC, liquid chromatography; LSC, liquid scintillation counting; MS, mass spectrometry; RAD, radiochemical detection; RLMs, rat liver microsomes; TDI, time-dependent inhibition 2 DMD Fast Forward. -
Toxicology Solutions
Toxicology Solutions Contents Biochip Array Technology Overview 04 Benefits 05 Testing Process 06 The Evidence Series 08 Evidence+ 10 Evidence 12 Evidence Investigator 14 Evidence MultiSTAT 16 Matrices 18 Test Menu 20 Customisable Test Menu 24 Catalogue Numbers 26 ELISA 28 Cross Reactivity 30 Technical Support 37 Ordering Information 38 Introduction Randox Toxicology aim to minimise laboratory workflow constraints whilst maximising the scope of quality drug detection. We are the primary manufacturer of Biochip Array Technology, ELISAs, and automated systems for forensic, clinical and workplace toxicology. Biochip Array Technology Moving away from traditional single analyte assays, Biochip Array Technology (BAT) boasts cutting-edge multiplex testing capabilities providing rapid and accurate drug detection from a single sample. Based on ELISA principles, the Biochip is a solid state device with discrete test regions onto which antibodies, specific to different drug compounds, are immobilised and stabilised. Competitive chemiluminescent immunoassays are then employed, offering a highly sensitive screen. Designed to work across a wide variety of matrices, this revolutionary multi- analyte testing platform allows toxicologists to achieve a complete immunoassay profile from the initial screening phase. Offering the most advanced screening technology on the market, Randox Toxicology has transformed the landscape of drugs of abuse (DoA) testing. Our unrivalled toxicology test menu is capable of detecting over 500 drugs and drug metabolites. 4 Benefits Simultaneous detection Multiplex testing facilitates simultaneous screening of various drugs and drug metabolites from a single sample. Accurate testing Biochip Array Technology has a proven high standard of accurate test results with CVs typically <10%. Small sample volume As little as 6μl of sample produces a complete immunoassay profile, leaving more for confirmatory testing. -
Potential Cannabis Antagonists for Marijuana Intoxication
Central Journal of Pharmacology & Clinical Toxicology Bringing Excellence in Open Access Review Article *Corresponding author Matthew Kagan, M.D., Cedars-Sinai Medical Center, 8730 Alden Drive, Los Angeles, CA 90048, USA, Tel: 310- Potential Cannabis Antagonists 423-3465; Fax: 310.423.8397; Email: Matthew.Kagan@ cshs.org Submitted: 11 October 2018 for Marijuana Intoxication Accepted: 23 October 2018 William W. Ishak, Jonathan Dang, Steven Clevenger, Shaina Published: 25 October 2018 Ganjian, Samantha Cohen, and Matthew Kagan* ISSN: 2333-7079 Cedars-Sinai Medical Center, USA Copyright © 2018 Kagan et al. Abstract OPEN ACCESS Keywords Cannabis use is on the rise leading to the need to address the medical, psychosocial, • Cannabis and economic effects of cannabis intoxication. While effective agents have not yet been • Cannabinoids implemented for the treatment of acute marijuana intoxication, a number of compounds • Antagonist continue to hold promise for treatment of cannabinoid intoxication. Potential therapeutic • Marijuana agents are reviewed with advantages and side effects. Three agents appear to merit • Intoxication further inquiry; most notably Cannabidiol with some evidence of antipsychotic activity • THC and in addition Virodhamine and Tetrahydrocannabivarin with a similar mixed receptor profile. Given the results of this research, continued development of agents acting on cannabinoid receptors with and without peripheral selectivity may lead to an effective treatment for acute cannabinoid intoxication. Much work still remains to develop strategies that will interrupt and reverse the effects of acute marijuana intoxication. ABBREVIATIONS Therapeutic uses of cannabis include chronic pain, loss of appetite, spasticity, and chemotherapy-associated nausea and CBD: Cannabidiol; CBG: Cannabigerol; THCV: vomiting [8]. Recreational cannabis use is on the rise with more Tetrahydrocannabivarin; THC: Tetrahydrocannabinol states approving its use and it is viewed as no different from INTRODUCTION recreational use of alcohol or tobacco [9]. -
NIDA - Director's Report - May 2004
NIDA - Director's Report - May 2004 Home > Publications > Director's Reports Director's Report to the National Advisory Council on Drug Abuse - May, 2004 Index Report Index Research Findings Report for February, 2004 Basic Research Report for Behavioral Research September, 2003 Treatment Research and Development Report for May, Research on AIDS and Other Medical Consequences of Drug 2003 Abuse - AIDS Research Report for February, Research on AIDS and Other Medical Consequences of Drug 2003 Abuse - Non-AIDS Medical Consequences of Drug Abuse Report for Epidemiology and Etiology Research September, 2002 Prevention Research Report for May, 2002 Services Research Report for February, Intramural Research 2002 Program Activities Report for September, 2001 Extramural Policy and Review Activities Report for May, 2001 Congressional Affairs Report for February, 2001 International Activities Report for September, 2000 Meetings and Conferences Report for May, 2000 Media and Education Activities Report for February, 2000 Planned Meetings Report for September, 1999 Publications Report for May, 1999 Staff Highlights Report for February, 1999 Grantee Honors Report for September, 1998 Report for May, 1998 Report for February, 1998 Report for September, 1997 Report for May, 1997 Report for February, 1997 https://archives.drugabuse.gov/DirReports/DirRep504/Default.html[11/17/16, 10:22:07 PM] NIDA - Director's Report - May 2004 Report from September, 1996 Report from May, 1996 Report from February, 1996 Report from September, 1995 Report from May, 1995 Report from February, 1995 NACDA Legislation Archive Home | Accessibility | Privacy | FOIA (NIH) | Current NIDA Home Page The National Institute on Drug Abuse (NIDA) is part of the National Institutes of Health (NIH) , a component of the U.S. -
Cathinone-Derived Psychostimulants Steven J
Review Cite This: ACS Chem. Neurosci. XXXX, XXX, XXX−XXX pubs.acs.org/chemneuro DARK Classics in Chemical Neuroscience: Cathinone-Derived Psychostimulants Steven J. Simmons,*,† Jonna M. Leyrer-Jackson,‡ Chicora F. Oliver,† Callum Hicks,† John W. Muschamp,† Scott M. Rawls,† and M. Foster Olive‡ † Center for Substance Abuse Research (CSAR), Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania 19140, United States ‡ Department of Psychology, Arizona State University, Tempe, Arizona 85281, United States ABSTRACT: Cathinone is a plant alkaloid found in khat leaves of perennial shrubs grown in East Africa. Similar to cocaine, cathinone elicits psychostimulant effects which are in part attributed to its amphetamine-like structure. Around 2010, home laboratories began altering the parent structure of cathinone to synthesize derivatives with mechanisms of action, potencies, and pharmacokinetics permitting high abuse potential and toxicity. These “synthetic cathinones” include 4-methylmethcathinone (mephedrone), 3,4-methylenedioxypyrovalerone (MDPV), and the empathogenic agent 3,4-methylenedioxymethcathinone (methylone) which collectively gained international popularity following aggressive online marketing as well as availability in various retail outlets. Case reports made clear the health risks associated with these agents and, in 2012, the Drug Enforcement Agency of the United States placed a series of synthetic cathinones on Schedule I under emergency order. Mechanistically, cathinone and synthetic derivatives work by augmenting monoamine transmission through release facilitation and/or presynaptic transport inhibition. Animal studies confirm the rewarding and reinforcing properties of synthetic cathinones by utilizing self-administration, place conditioning, and intracranial self-stimulation assays and additionally show persistent neuropathological features which demonstrate a clear need to better understand this class of drugs. -
Antiobesity and Anti-Inflammation Effects of Hakka Stir-Fried Tea Of
food & nutrition research ORIGINAL ARTICLE Antiobesity and anti-inflammation effects of Hakka stir-fried tea of different storage years on high-fat diet-induced obese mice model via activating the AMPK/ACC/CPT1 pathway Qiuhua Li1, Xingfei Lai1, Lingli Sun1, Junxi Cao1, Caijin Ling1, Wenji Zhang1, Limin Xiang1, Ruohong Chen1, Dongli Li2* and Shili Sun1* 1Tea Research Institute, Guangdong Academy of Agricultural Sciences/Guangdong Provincial Key Laboratory of Tea Plant Resources Innovation & Utilization, Guangzhou, China; 2School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China Popular scientific summary • We confirmed that HT treatment significantly reduced body weight and fat accumulation in major organs in high-fat diet-induced obese mice. • The effects of HT appear to be mediated by the activation of AMPK/ACC/CPT-1 pathway and further inhibiting lipogenesis. • Our findings suggest that HT may be used as a potential dietary strategy for preventing obesity and related metabolic disorder diseases. Abstract Background: As a typical representative of metabolic syndrome, obesity is also one of the extremely danger- ous factors of cardiovascular diseases. Thus, the prevention and treatment of obesity has gradually become a global campaign. There have been many reports that green tea is effective in preventing obesity, but as a kind of green tea with regional characteristics, there have been no reports that Hakka stir-fried tea (HT) of different storage years has a weight loss effect. Aims: The aim was to investigate the effect of HT in diet-induced obese mice. Methods: The mice were divided into five groups as follows: the control group received normal diet; the obese model group received high-fat diet; and HT2003, HT2008, and HT2015 groups, after the induction of obesity via a high-fat diet, received HT of different storage years treatment for 6 weeks, respectively. -
Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanismss
Supplemental Material can be found at: /content/suppl/2020/12/18/73.1.202.DC1.html 1521-0081/73/1/202–277$35.00 https://doi.org/10.1124/pharmrev.120.000056 PHARMACOLOGICAL REVIEWS Pharmacol Rev 73:202–277, January 2021 Copyright © 2020 by The Author(s) This is an open access article distributed under the CC BY-NC Attribution 4.0 International license. ASSOCIATE EDITOR: MICHAEL NADER Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanismss Antonio Inserra, Danilo De Gregorio, and Gabriella Gobbi Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec, Canada Abstract ...................................................................................205 Significance Statement. ..................................................................205 I. Introduction . ..............................................................................205 A. Review Outline ........................................................................205 B. Psychiatric Disorders and the Need for Novel Pharmacotherapies .......................206 C. Psychedelic Compounds as Novel Therapeutics in Psychiatry: Overview and Comparison with Current Available Treatments . .....................................206 D. Classical or Serotonergic Psychedelics versus Nonclassical Psychedelics: Definition ......208 Downloaded from E. Dissociative Anesthetics................................................................209 F. Empathogens-Entactogens . ............................................................209 -
Anxiolytic-Like Activity of SB-205384 in the Elevated Plus Maze Test in Mice
Psicothema 2006. Vol. 18, nº 1, pp. 100-104 ISSN 0214 - 9915 CODEN PSOTEG www.psicothema.com Copyright © 2006 Psicothema Anxiolytic-like activity of SB-205384 in the elevated plus maze test in mice José Francisco Navarro, Estrella Burón and Mercedes Martín-López Universidad de Málaga Recent studies point to a major role for α2-containing GABA-A receptors in modulating anxiety. Ho- wever, the possible implication of GABA-A receptors containing the α3 subunit on anxiety is less known. The aim of this study was to examine the effects of SB-205384 (0.5-4 mg/kg, ip), an α3 su- bunit positive modulator of GABA-A receptor, on anxiety tested in the elevated plus-maze in male mi- ce, using classical and ethological parameters. Mice treated with SB-205384 showed an increase in the frequency of entries and the time spent in open arms, as well as a reduction in the time spent in closed arms, as compared with the control group. A notable increase of «head-dipping» unprotected and a re- duction of «stretched-attend posture» protected was also evident. These findings indicate that SB- 205384 exhibits an anxiolytic-like profile in the elevated plus-maze test, suggesting that GABA-A re- ceptors which contain the α3 subunit might be involved in regulation anxiety. Actividad ansiolítica del SB-205384 en el laberinto elevado en cruz en ratones. Recientes investiga- ciones indican que los receptores GABA-A que contienen subunidades α2 desempeñan un importan- te papel en la modulación de la ansiedad. Sin embargo, la posible implicación de los receptores GA- BA-A que contienen la subunidad α3 es menos conocida. -
The Endocannabinoid System and Psychiatric Disorders
Experimental Neurology 224 (2010) 3–14 Contents lists available at ScienceDirect Experimental Neurology journal homepage: www.elsevier.com/locate/yexnr Review The endocannabinoid system and psychiatric disorders Daniela Parolaro a,b,⁎, Natalia Realini a, Daniela Vigano a,b, Cinzia Guidali a, Tiziana Rubino a a DBSF and Neuroscience Center, University of Insubria, Via A. da Giussano 10, 21052 Busto Arsizio (Varese), Italy b Zardi-Gori Foundation, via P.Cossa 1, Milan, Italy article info abstract Available online 29 March 2010 The present review summarizes the latest information on the role and the pharmacological modulation of the endocannabinoid system in mood disorders and its potential implication in psychotic disorders such as Keywords: schizophrenia. Endocannabinoid system Reduced functionality might be considered a predisposing factor for major depression, so boosting Depression endocannabinoid tone might be a useful alternative therapeutic approach for depressive disorders. The Anxiety picture regarding endocannabinoids and anxiety is more complicated since either too much or too little Schizophrenia anandamide can lead to anxiety states. However, a small rise in its level in specific brain areas might be beneficial for the response to a stressful situation and therefore to tone down anxiety. This effect might be achieved with low doses of cannabinoid indirect agonists, such as blockers of the degradative pathway (i.e. FAAH) or re-uptake inhibitors. Moreover several lines of experimental and clinical evidence point to a dysregulation of the endocanna- binoid system in schizophrenia. The high anandamide levels found in schizophrenic patients, negatively correlated with psychotic symptoms, point to a protective role, whereas the role of 2-arachidonoyl glycerol is still unclear. -
The Use of Cannabinoids in Animals and Therapeutic Implications for Veterinary Medicine: a Review
Veterinarni Medicina, 61, 2016 (3): 111–122 Review Article doi: 10.17221/8762-VETMED The use of cannabinoids in animals and therapeutic implications for veterinary medicine: a review L. Landa1, A. Sulcova2, P. Gbelec3 1Faculty of Medicine, Masaryk University, Brno, Czech Republic 2Central European Institute of Technology, Masaryk University, Brno, Czech Republic 3Veterinary Hospital and Ambulance AA Vet, Prague, Czech Republic ABSTRACT: Cannabinoids/medical marijuana and their possible therapeutic use have received increased atten- tion in human medicine during the last years. This increased attention is also an issue for veterinarians because particularly companion animal owners now show an increased interest in the use of these compounds in veteri- nary medicine. This review sets out to comprehensively summarise well known facts concerning properties of cannabinoids, their mechanisms of action, role of cannabinoid receptors and their classification. It outlines the main pharmacological effects of cannabinoids in laboratory rodents and it also discusses examples of possible beneficial use in other animal species (ferrets, cats, dogs, monkeys) that have been reported in the scientific lit- erature. Finally, the article deals with the prospective use of cannabinoids in veterinary medicine. We have not intended to review the topic of cannabinoids in an exhaustive manner; rather, our aim was to provide both the scientific community and clinical veterinarians with a brief, concise and understandable overview of the use of cannabinoids in veterinary