Endocannabinoids: Molecular, Pharmacological, Behavioral and Clinical Features
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Endocannabinoids: Molecular, Pharmacological, Behavioral and Clinical Features Editor Eric Murillo-Rodríguez Laboratory of Molecular and Integrative Neurosciences School of Medicine, Health Sciences Division Anahuac University Mayab Merida 97310 Yucatan, Mexico Co-Editors Emmanuel S. Onaivi William Paterson University, USA Nissar A. Darmani Western University of Health Sciences, USA Edward Wagner Western University of Health Sciences, USA Bentham Science Publishers Bentham Science Publishers Bentham Science Publishers Executive Suite Y - 2 P.O. Box 446 P.O. Box 294 PO Box 7917, Saif Zone Oak Park, IL 60301-0446 1400 AG Bussum Sharjah, U.A.E. USA THE NETHERLANDS [email protected] [email protected] [email protected] Please read this license agreement carefully before using this eBook. Your use of this eBook/chapter constitutes your agreement to the terms and conditions set forth in this License Agreement. 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Permission for Use of Material and Reproduction Photocopying Information for Users Outside the USA: Bentham Science Publishers grants authorization for individuals to photocopy copyright material for private research use, on the sole basis that requests for such use are referred directly to the requestor's local Reproduction Rights Organization (RRO). The copyright fee is US $25.00 per copy per article exclusive of any charge or fee levied. In order to contact your local RRO, please contact the International Federation of Reproduction Rights Organisations (IFRRO), Rue Joseph II, 9-13 I000 Brussels, Belgium; Tel: +32 2 234 62 60; Fax: +32 2 234 62 69; E-mail: [email protected]; url: www.ifrro.org This authorization does not extend to any other kind of copying by any means, in any form, and for any purpose other than private research use. Photocopying Information for Users in the USA: Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Bentham Science Publishers for libraries and other users registered with the Copyright Clearance Center (CCC) Transactional Reporting Services, provided that the appropriate fee of US $25.00 per copy per chapter is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers MA 01923, USA. Refer also to www.copyright.com CONTENTS About the eBook i Foreword ii Preface vi Acknowledgements viii List of Contributors ix CHAPTERS PART I: ENDOCANNABINOIDS: MOLECULAR FEATURES 1. Cannabinoid Receptor Gene Variations in Neuropsychiatric Disorders 3 Hiroki Ishiguro, Claire M. Leonard, Susan Sgro and Emmanuel S. Onaivi 2. The Role of Endocannabinoids and Arachidonic Acid Metabolites in Emesis 25 Nissar A. Darmani and Seetha Chebolu 3. On the Cannabinoid Regulation of Energy Homeostasis: Past, Present and Future 60 Amanda Borgquist and Edward J. Wagner PART II: ENDOCANNABINOIDS: BIOCHEMICAL, PHARMACOLOGICAL AND CLINICAL FEATURES 4. Structural Biology of Endocannabinoid Targets and Enzymes: Components Tuned to the Flexibility of Endogenous Ligands 92 Dow P. Hurst, Jagjeet Singh and Patricia H. Reggio 5. Dynamic Interactions Between Drugs of Abuse and the Endocannabinoid System: Molecular Mechanisms and Functional Outcome 132 Miriam Melis, Anna L. Muntoni and Marco Pistis 6. The Development of Cannabinoid Based Therapies for Epilepsy 164 Andrew J. Hill, Thomas D.M. Hill and Benjamin J. Whalley Index 205 i About the eBook The endocannabinoid system comprises at least two G-protein-coupled receptors (the cannabinoid CB1 and CB2 receptors) activated by marijuana’s psychoactive principle ∆9-tetrahydrocannabinol (THC) and the endogenous ligands known as endocannabinoids. The apex of endocannabinoid research seems to have been reached with the clinical development, and in some cases also the marketing, of synthetic or natural pharmaceuticals targeting this signalling system, which followed the understanding of its physiological and pathological role in several conditions, a role that was investigated first in rodent experimental models and then in humans. We particularly take an interest in Manuscripts that report relevance of the endocannabinoid system. Original reports or Reviews describing the results of experimental evidence about the neurobiological role of the endocannabinoid system would be a great interest. Main topics include, but are not limited to: *The genetics of cannabinoid CB1 and CB2 receptors and their tissue distribution, their splicing variants and polymorphisms, and the possible implications of all this in determining different behaviours as well as various pathological conditions and the addiction to substances of abuse. *Pharmacological approaches describing the potential use in the central nervous system disorders of endocannabinoid-based drugs, such as cannabinoid receptor agonists and antagonists, inhibitors of endocannabinoid inactivation processes, and even plant cannabinoids other than THC and with a molecular mechanism of action. *The role of the endocannabinoid system in several neurological and neuropsychiatric conditions, such as epilepsy. Key feature: Cannabinoid receptor genes, arachidonic acid, homeostasis, drugs of abuse, neurogenesis, epilepsy. INTENDED AUDIENCE/READERSHIP The areas of interest would include genetics, molecular biology, biochemistry, pharmacology. Contributions may involve clinical, preclinical, or basic research. ii FOREWORD For me, personally, the year 2013 has a special significance. Exactly 50 years ago I published my first paper on cannabinoids. At that time, in 1963, research on the constituents of Cannabis sativa had mostly come to a stop. Although investigation on cannabis in its various forms –hashish, marijuana, bhang – had been reported over a century, its psychoactive constituent(s) had not been isolated in a pure form and its structure – or possibly structures – was unknown. And yet, there was no research going on in either North America or the UK – the major research countries at the time.