Cannabinoids for the Control of Experimental Multiple Sclerosis Pryce, Gareth
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Targeting the Endocannabinoid System to Reduce Nociception
Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2011 Targeting the endocannabinoid system to reduce nociception Lamont Booker Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Medical Pharmacology Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/2419 This Dissertation is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. Targeting the Endocannabinoid System to Reduce Nociception A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. By Lamont Booker Bachelor’s of Science, Fayetteville State University 2003 Master’s of Toxicology, North Carolina State University 2005 Director: Dr. Aron H. Lichtman, Professor, Pharmacology & Toxicology Virginia Commonwealth University Richmond, Virginia April 2011 Acknowledgements The author wishes to thank several people. I like to thank my advisor Dr. Aron Lichtman for taking a chance and allowing me to work under his guidance. He has been a great influence not only with project and research direction, but as an excellent example of what a mentor should be (always willing to listen, understanding the needs of each student/technician, and willing to provide a hand when available). Additionally, I like to thank all of my committee members (Drs. Galya Abdrakmanova, Francine Cabral, Sandra Welch, Mike Grotewiel) for your patience and willingness to participate as a member. Our term together has truly been memorable! I owe a special thanks to Sheryol Cox, and Dr. -
Cannabinoid-Induced Hypotension and Bradycardia in Rats Is 1 Mediated by CB1-Like Cannabinoid Receptors
0022-3565/97/2813-1030$03.00/0 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 281, No. 3 Copyright © 1997 by The American Society for Pharmacology and Experimental Therapeutics Printed in U.S.A. JPET 281:1030–1037, 1997 Cannabinoid-Induced Hypotension and Bradycardia in Rats Is 1 Mediated by CB1-Like Cannabinoid Receptors KRISTY D. LAKE, DAVID R. COMPTON, KAROLY VARGA, BILLY R. MARTIN and GEORGE KUNOS Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia Accepted for publication February 19, 1997 ABSTRACT 9 Previous studies indicate that the CB1 cannabinoid receptor an- potency was (-)-11-OH-D -THC dimethylheptyl $ (-)-3-[2- tagonist, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophe- hydroxy-4-(1,1-dimethyl-heptyl)phenyl]-4-[3-hydroxy-propyl]cy- nyl)-4-methyl-1H-pyrazole-3-carboxamide HCl (SR141716A), in- clohexan-1-ol . (-)-3-[2-hydroxy-4-(1,1-dimethyl-heptyl)phenyl]- hibits the anandamide- and D9-tetrahydrocannabinol- (THC) 4-[3-hydroxy-propyl]cyclohexan-1-ol . THC . anandamide $ induced hypotension and bradycardia in anesthetized rats with a (-)-3-[2-hydroxy-4-(1,1-dimethyl-heptyl)phenyl]-4-[3-hydroxy- potency similar to that observed for SR141716A antagonism of propyl]cyclohexan-1-ol, which correlated well with CB1 receptor THC-induced neurobehavioral effects. To further test the role of affinity or analgesic potency (r 5 0.96-0.99). There was no hypo- CB1 receptors in the cardiovascular effects of cannabinoids, we tension or bradycardia after palmitoylethanolamine or (1)-11-OH- examined two additional criteria for receptor-specific interactions: D9-THC dimethylheptyl. -
Medicinal Chemistry Endeavors Around the Phytocannabinoids
CHEMISTRY & BIODIVERSITY – Vol. 4 (2007) 1707 REVIEW Medicinal Chemistry Endeavors around the Phytocannabinoids by Eric Stern and Didier M. Lambert* Drug Design and Discovery Center and Unite´ de Chimie pharmaceutique et de Radiopharmacie, Ecole de Pharmacie, Faculte´ de Me´decine, Universite´ catholique de Louvain, Avenue E. Mounier 73, U.C.L. 73.40, B-1200 Bruxelles (phone: þ3227647347; fax: þ3227647363; e-mail: [email protected]) Over the past 50 years, a considerable research in medicinal chemistry has been carried out around the natural constituents of Cannabis sativa L. Following the identification of D9-tetrahydrocannabinol (D9-THC) in 1964, critical chemical modifications, e.g., variation of the side chain at C(3) and the opening of the tricyclic scaffold, have led to the characterization of potent and cannabinoid receptor subtype-selective ligands. Those ligands that demonstrate high affinity for the cannabinoid receptors and good biological efficacy are still used as powerful pharmacological tools. This review summarizes past as well as recent developments in the structure–activity relationships of phytocannabinoids. 1. Introduction. – Despite the wide uses of preparations of the hemp Cannabis sativa L. during the History, the modern pharmacology of natural cannabinoids has been hampered by the slow progress in the elucidations of the chemical structures of its major components. Indeed, it is nowadays known that more than 70 compounds derived from a diterpene structure are present in the plant [1], and this fact may explain the difficulty to obtain pure chemical entities in the past. In addition, the medicinal research for more than a half century has been driven by the search for the components responsible for the psychoactive effects of cannabis, this era in the history of the chemical research on cannabinoids have been recently reviewed [2][3]. -
Application of High Resolution Mass Spectrometry for the Screening and Confirmation of Novel Psychoactive Substances Joshua Zolton Seither [email protected]
Florida International University FIU Digital Commons FIU Electronic Theses and Dissertations University Graduate School 4-25-2018 Application of High Resolution Mass Spectrometry for the Screening and Confirmation of Novel Psychoactive Substances Joshua Zolton Seither [email protected] DOI: 10.25148/etd.FIDC006565 Follow this and additional works at: https://digitalcommons.fiu.edu/etd Part of the Chemistry Commons Recommended Citation Seither, Joshua Zolton, "Application of High Resolution Mass Spectrometry for the Screening and Confirmation of Novel Psychoactive Substances" (2018). FIU Electronic Theses and Dissertations. 3823. https://digitalcommons.fiu.edu/etd/3823 This work is brought to you for free and open access by the University Graduate School at FIU Digital Commons. It has been accepted for inclusion in FIU Electronic Theses and Dissertations by an authorized administrator of FIU Digital Commons. For more information, please contact [email protected]. FLORIDA INTERNATIONAL UNIVERSITY Miami, Florida APPLICATION OF HIGH RESOLUTION MASS SPECTROMETRY FOR THE SCREENING AND CONFIRMATION OF NOVEL PSYCHOACTIVE SUBSTANCES A dissertation submitted in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in CHEMISTRY by Joshua Zolton Seither 2018 To: Dean Michael R. Heithaus College of Arts, Sciences and Education This dissertation, written by Joshua Zolton Seither, and entitled Application of High- Resolution Mass Spectrometry for the Screening and Confirmation of Novel Psychoactive Substances, having been approved in respect to style and intellectual content, is referred to you for judgment. We have read this dissertation and recommend that it be approved. _______________________________________ Piero Gardinali _______________________________________ Bruce McCord _______________________________________ DeEtta Mills _______________________________________ Stanislaw Wnuk _______________________________________ Anthony DeCaprio, Major Professor Date of Defense: April 25, 2018 The dissertation of Joshua Zolton Seither is approved. -
Icrs2015 Programme
TH 25 ANNUAL SYMPOSIUM OF THE INTERNATIONAL CANNABINOID RESEARCH SOCIETY WOLFVILLE NOVA SCOTIA JUNE 28 - JULY 3, 2015 TH 25 ANNUAL SYMPOSIUM OF THE INTERNATIONAL CANNABINOID RESEARCH SOCIETY WOLFVILLE JUNE 28 – JULY 3, 2015 Symposium Programming by Cortical Systematics LLC Copyright © 2015 International Cannabinoid Research Society Research Triangle Park, NC USA ISBN: 978-0-9892885-2-1 These abstracts may be cited in the scientific literature as follows: Author(s), Abstract Title (2015) 25th Annual Symposium on the Cannabinoids, International Cannabinoid Research Society, Research Triangle Park, NC, USA, Page #. Funding for this conference was made possible in part by grant 5R13DA016280-13 from the National Institute on Drug Abuse. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government. Sponsors ICRS Government Sponsors National Institute on Drug Abuse Non- Profit Organization Sponsors Kang Tsou Memorial Fund 2015 ICRS Board of Directors Executive Director Cecilia Hillard, Ph.D. President Stephen Alexander, Ph.D. President- Elect Michelle Glass, Ph.D. Past President Ethan Russo, M.D. Secretary Steve Kinsey, Ph.D. Treasurer Mary Abood, Ph.D. International Secretary Roger Pertwee, D . Phil. , D . S c. Student Representative Tiffany Lee, Ph.D. Grant PI Jenny Wiley, Ph.D. Managing Director Jason Schechter, Ph.D. 2015 Symposium on the Cannabinoids Conference Coordinators Steve Alexander, Ph.D. Cecilia Hillard, Ph.D. Mary Lynch, M.D. Jason Schechter, Ph.D. -
Effects of Abnormal Cannabidiol on Oxytocin-Induced Myometrial Contractility
REPRODUCTIONRESEARCH Effects of abnormal cannabidiol on oxytocin-induced myometrial contractility Diarmaid D Houlihan, Michael C Dennedy and John J Morrison Department of Obstetrics and Gynecology, Clinical Sciences Institute, University College Hospital, National University of Ireland Galway, Newcastle Road, Galway, Ireland Correspondence should be addressed to J J Morrison; Email: [email protected] Abstract The objective of this study was to investigate the effects of abnormal cannabidiol (abn-cbd) on oxytocin-induced myometrial contractility occurring during pregnancy. Isometric tension recordings were performed in isolated myometrial strips from biopsies obtained at K K elective cesarean section. The effects of cumulative doses of abn-cbd (10 9–10 5 M) on oxytocin-induced myometrial contractions alone, and on those following pre-incubation with SR 144528, AM 251, methylene blue, and iberiotoxin were measured, and dose– K response curves were constructed. The pD2 ( log EC50) values and the maximal inhibitory (MMI) values that were achieved were compared for each tissue type. Abn-cbd exerted a potent relaxant effect on oxytocin-induced myometrial contractions in vitro. Pre-incubation with the guanylate cyclase inhibitor, methylene blue, and the BKCa channel antagonist, iberiotoxin, significantly ! ! attenuated this effect (for pD2, P 0.01; for MMI, P 0.01). Abn-cbd exerts a potent inhibitory effect on human uterine contractility. This effect is partially mediated through modulation of guanylate cyclase and activation of BKCa channel activity. These findings have implications for physiologic regulation of myometrial quiescence. Reproduction (2010) 139 783–788 Introduction regioisomer of cannabidiol, which mediates a relaxant effect in isolated rat mesenteric artery via a mechanism The endocannabinoids comprise a family of eicosanoid that is distinct from CB1 and CB2 receptor activation and related unsaturated fatty acid derivatives, of which (Jarai et al. -
Expression of Cannabinoid Receptors in Human Osteoarthritic Cartilage
Expression of cannabinoid receptors in human osteoarthritic cartilage: implications for future therapies DUNN, Sara L., WILKINSON, Jeremy Mark, CRAWFORD, Aileen, BUNNING, Rowena A.D. <http://orcid.org/0000-0003-3110-0445> and LE MAITRE, Christine L. <http://orcid.org/0000-0003-4489-7107> Available from Sheffield Hallam University Research Archive (SHURA) at: http://shura.shu.ac.uk/11794/ This document is the author deposited version. You are advised to consult the publisher's version if you wish to cite from it. Published version DUNN, Sara L., WILKINSON, Jeremy Mark, CRAWFORD, Aileen, BUNNING, Rowena A.D. and LE MAITRE, Christine L. (2016). Expression of cannabinoid receptors in human osteoarthritic cartilage: implications for future therapies. Cannabis and Cannabinoid Research, 1 (1), 3-15. Copyright and re-use policy See http://shura.shu.ac.uk/information.html Sheffield Hallam University Research Archive http://shura.shu.ac.uk Cannabis and Cannabinoid Research Volume 1.1, 2016 Cannabis and DOI: 10.1089/can.2015.0001 Cannabinoid Research ORIGINAL RESEARCH Open Access Expression of Cannabinoid Receptors in Human Osteoarthritic Cartilage: Implications for Future Therapies Sara L. Dunn,1 Jeremy Mark Wilkinson,2 Aileen Crawford,3 Rowena A.D. Bunning,1 and Christine L. Le Maitre1,* Abstract Introduction: Cannabinoids have shown to reduce joint damage in animal models of arthritis and reduce ma- trix metalloproteinase expression in primary human osteoarthritic (OA) chondrocytes. The actions of cannabi- noids are mediated by a number of receptors, including cannabinoid receptors 1 and 2 (CB1 and CB2), G- protein-coupled receptors 55 and 18 (GPR55 and GPR18), transient receptor potential vanilloid-1 (TRPV1), and peroxisome proliferator-activated receptors alpha and gamma (PPARa and PPARc). -
Laws, Rules, and Regulations
LAWS, RULES, AND REGULATIONS August 2020 Asa Hutchinson, Governor John Clay Kirtley, Pharm.D. Executive Director Arkansas Department of Health Arkansas State Board of Pharmacy 322 South Main Street, Suite 600 Little Rock, AR 72201 Phone: 501.682.0190 Fax: 501.682.0195 [email protected] www.pharmacyboard.arkansas.gov 10/8/2020 Arkansas State Board of Pharmacy Members Lenora Newsome, P.D. President, Smackover Rebecca Mitchell, Pharm.D. Vice President/Secretary, Greenbrier Deborah Mack, P.D. Member, Bentonville Lynn Crouse, Pharm.D. Member, Lake Village Brian Jolly, Pharm.D. Member, Beebe Carol Rader, RN Public Member, Fort Smith Amy Fore, MHSA, FACMPE, FACHE Public Member, Fort Smith 10/8/2020 Board of Pharmacy Law Book - Acts Table of Contents Pharmacy Practice Act A 17-92-101 Definitions……………………………………………………… 1-4 17-92-102 Exemptions…………………………………………………….. 4-5 17-92-103 Pharmacy laws unaffected……………………………………... 5 17-92-104 Privilege tax unaffected……………………………………….. 5 17-92-105 Prohibited acts – Penalties……………………………………... 6 17-92-106 Injunctions……………………………………………………… 6 17-92-107 Prosecutions – Disposition of fines……………………………. 6 17-92-108 Fees…………………………………………………………….. 6-10 17-92-109 Prescriptions for optometrists………………………………….. 10 17-92-110 Prescriptive authority of advance practice nurses……………… 10 17-92-111 Construction of Acts 1997, No. 1204………………………….. 10 17-92-112 Prescriptions for physician assistants…………………………. 10 17-92-201 Members – Qualifications……………………………………… 11 17-92-202 Members – Oath……………………………………………… 11 17-92-203 Members – Compensation…………………………………….. 11 17-92-204 Organization and proceedings…………………………………. 12 17-92-205 Rules and regulations – Enforcement………………………….. 12-13 17-92-206 Issuance of bulletins – Annual Reports………………………... 14 17-92-207 Maintenance of office…………………………………………. -
Cannabinoid Receptors and Endocannabinoids
The AAPS Journal 2006; 8 (2) Article 34 (http://www.aapsj.org). Themed Issue: Lipid Mediator Lipidomics: New Pathways in Mapping Resolution Guest Editors - Charles N. Serhan, Song Hong and Yan Lu Cannabinoid Receptors and Endocannabinoids: Evidence for New Players Submitted: December 29 , 2005 ; Accepted: February 28 , 2006; Published: April 28, 2006 Ken Mackie1 and Nephi Stella2 1 Departments of Anesthesiology and Physiology and Biophysics, University of Washington, Seattle WA 2 Departments of Pharmacology, Psychiatry, and Behavioral Sciences, University of Washington, Seattle, WA A BSTRACT nabinoids, and are getting much closer to overcoming It is now well established that the psychoactive effects of these 2 challenges. Cannabis sativa are primarily mediated through neuronal C sativa contains ~60 phytocannabinoids, a handful of which CB1 receptors, while its therapeutic immune properties are bioactive as defi ned by their ability to specifi cally inter- are primarily mediated through CB2 receptors. Two endo- act with membrane-associated receptors, the cannabinoid cannabinoids, arachidonoylethanolamide and 2-arachi- receptors. The best-known phytocannabinoid is Δ 9 -tetrahy- donoylglycerol, have been identifi ed, their action on CB1 drocannabinol (THC),3 which is thought to mediate most — if and CB2 thoroughly characterized, and their production not all — of the psychotropic and addictive properties of C and inactivation elucidated. However, many signifi cant sativa . 4 Recent evidence suggest that some of the antiinfl am- exceptions to these -
Pharmacological Actions of Cannabinoids
Pharmacological Actions of Cannabinoids R.G. Pertwee School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK [email protected] 1Introduction.................................... 2 2 Bioassays for Characterizing CB1 and CB2 Receptor Ligands .......... 6 2.1 InVitroBindingAssays.............................. 6 2.2 In Vitro Functional Bioassays .......................... 9 2.2.1AssaysUsingWholeCellsorCellMembranes.................. 9 2.2.2IsolatedNerve–SmoothMusclePreparations.................. 11 2.3 In Vivo Bioassays ................................. 11 2.4 CannabinoidReceptorKnockoutMice...................... 12 3CB1 and CB2 Cannabinoid Receptor Ligands .................. 13 3.1 CannabinoidReceptorAgonists......................... 13 3.2 Cannabinoid CB1 and CB2 ReceptorAntagonists................ 20 3.2.1 Selective CB1 ReceptorAntagonists....................... 20 3.2.2 Selective CB2 ReceptorAntagonists........................ 22 3.3 InverseAgonismatCannabinoidReceptors................... 22 3.4 NeutralAntagonismatCannabinoidReceptors................. 24 4 Other Pharmacological Targets for Cannabinoids in Mammalian Tissues ... 26 4.1 Receptors...................................... 26 4.1.1VanilloidReceptors................................ 26 4.1.2 CB1 ReceptorSubtypes.............................. 27 4.1.3 CB2-LikeReceptors................................ 27 4.1.4 Neuronal Non-CB1,Non-CB2,Non-TRPV1Receptors ............. 28 4.1.5ReceptorsforAbnormal-Cannabidiol..................... -
THC Reduces Ki67-Immunoreactive Cells Derived from Human Primary Glioblastoma in a GPR55-Dependent Manner
cancers Article THC Reduces Ki67-Immunoreactive Cells Derived from Human Primary Glioblastoma in a GPR55-Dependent Manner Marc Richard Kolbe 1, Tim Hohmann 1 , Urszula Hohmann 1 , Chalid Ghadban 1, Ken Mackie 2, Christin Zöller 3, Julian Prell 3, Jörg Illert 3, Christian Strauss 3 and Faramarz Dehghani 1,* 1 Department of Anatomy and Cell Biology, Medical Faculty of Martin-Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108 Halle (Saale), Germany; [email protected] (M.R.K.); [email protected] (T.H.); [email protected] (U.H.); [email protected] (C.G.) 2 Department of Psychological & Brain Sciences, Indiana University, 1101E. 10th, Bloomington, IN 47405, USA; [email protected] 3 Department of Neurosurgery, University Hospital Halle (Saale), Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany; [email protected] (C.Z.); [email protected] (J.P.); [email protected] (J.I.); [email protected] (C.S.) * Correspondence: [email protected]; Tel.: +49-345-557-1707 Simple Summary: Glioblastoma (GBM) is the most frequent primary brain tumor entity with poor prognosis and resistance to current standard therapies. Cannabinoids, such as tetrahydrocannabinol (THC) and cannabidiol (CBD) are discussed as promising compounds for individualized treatment, as they exert anti-tumor effects by binding to cannabinoid-specific receptors. However, their phar- Citation: Kolbe, M.R.; Hohmann, T.; Hohmann, U.; Ghadban, C.; Mackie, macology is highly diverse and complex. The present study was designed to verify (1) whether K.; Zöller, C.; Prell, J.; Illert, J.; Strauss, cannabinoids show even any effect in GBM cells derived from primary human tumor samples and C.; Dehghani, F. -
Time-Dependent Vascular Actions of Cannabidiol in the Rat Aorta
European Journal of Pharmacology 612 (2009) 61–68 Contents lists available at ScienceDirect European Journal of Pharmacology journal homepage: www.elsevier.com/locate/ejphar Cardiovascular Pharmacology Time-dependent vascular actions of cannabidiol in the rat aorta Saoirse E. O'Sullivan a,⁎, Yan Sun b, Andrew J. Bennett b, Michael D. Randall b, David A. Kendall b a School of Graduate Entry Medicine and Health, Derby City General Hospital, University of Nottingham, Derby DE22 3DT, United Kingdom b School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, United Kingdom article info abstract Article history: We have shown that the major active agent of Cannabis sativa, Δ9-tetrahydrocannabinol, activates Received 31 October 2008 peroxisome proliferator-activated receptor gamma [PPARγ, O'Sullivan, S.E., Tarling, E.J., Bennett, A.J., Kendall, Received in revised form 18 February 2009 D.A., Randall, M.D., 2005c. Novel time-dependent vascular actions of delta9-tetrahydrocannabinol mediated Accepted 3 March 2009 by peroxisome proliferator-activated receptor gamma. Biochem. Biophys. Res. Commun. 337, 824–831]. The Available online 11 March 2009 aim of the present study was to investigate whether another pharmacologically active phytocannabinoid, cannabidiol, similarly activates PPAR . Functional vascular studies were carried out in rat aortae in vitro by Keywords: γ Cannabinoid myography. PPARγ activation was investigated using reporter gene assays, a PPARγ competition-binding Cannabidiol assay and an adipogenesis assay. Cannabidiol caused time-dependent (over 2 h) vasorelaxation of pre- Aorta constricted aortae, sensitive to PPARγ antagonism (GW9662, 1 µM) and super oxide dismutase inhibition. Vasorelaxation The vascular effects of cannabidiol were not affected by endothelial denudation, nitric oxide synthase Peroxisome proliferator-activated receptor inhibition, pertussis toxin, cannabinoid CB1 or cannabinoid CB2 receptor antagonism, or capsaicin pre- gamma treatment.