Vicenzo Di MarzoEndocannabinoid Research Group, Pozzuoli, Italy

• List of Contributors xiiiPreface xv1 Looking ahead after 50 years of research on cannabinoids 1Raphael Mechoulam1.1 Summary 11.2 Introduction 11.3 Cannabidiol (CBD) 61.4 Fatty acid amides of amino acids and related compounds 81.5 Conclusions 101.6 References 102 Cannabinoid receptor intracellular signalling: The long journey from binding sites to biological effects 17Lawrence C. Blume, Khalil M. Eldeeb and Allyn C. Howlett2.1 Historical progression: Serendipity to opportunity 182.2 Significance of being a G protein coupled receptor (GPCR) 212.3 CB1 cannabinoid receptor interactions with other cellular signals 232.4 Functional role of CB1 receptor accessory proteins 252.5 Opportunities: Pharmacotherapeutic insights based on cell signalling 332.6 Concluding remarks 412.7 References 413 Endocannabinoid biochemistry: What do we know after 50 years? 53Filomena Fezza and Mauro Maccarrone3.1 Introduction 543.2 Endocannabinoids and related molecules 603.3 Biosynthesis of endocannabinoids and related molecules 663.4 Degradation of endocannabinoids 713.5 Oxidative metabolism of endocannabinoids 773.6 Conclusions and future perspectives 783.7 References 834 Genetic dissection of the endocannabinoid system and how it changed our knowledge of cannabinoid pharmacology and mammalian physiology 95Beat Lutz4.1 Introduction: To set the stage 964.2 Tool box for genetic dissection 974.3 Understanding cannabinoid pharmacology 1064.4 Unravelling endocannabinoid system functions 1134.5 Caveats in genetics 1244.6 What have we learnt about cannabinoid pharmacology and mammalian physiology? 1254.7 Perspectives 1274.8 References 1275 Cannabinoids, endocannabinoids and stress 139Cecilia J. Hillard, Qing-song Liu, XiaoQian Liu, Bin Pan, Christopher J. Roberts and Leyu Shi5.1 Introduction 1405.2 Regulation of endocannabinoid signalling by stress 1435.3 ECS regulation of the HPA axis response to stress 1545.4 ECS role in SNS responses to stress 1595.5 Stress and ECS in the periphery 1615.6 Summary 1625.7 References 1636 Cannabinoids and the brain: New hopes for new therapies 175Javier Fernández-Ruiz, Mariluz Hernández and Yolanda García-Movellán6.1 Cannabinoids and the brain: A long journey together 1766.2 Brain processes and brain disorders investigated in relation to the endocannabinoid system 1806.3 Concluding remarks and future perspectives 2026.4 References 2027 Potential therapeutic applications of cannabinoids in gastrointestinal and liver diseases: Focus on Δ9 -tetrahydrocannabinol pharmacology 219Paolo Caraceni, Francesca Borrelli, Ferdinando A. Giannone and Angelo A. Izzo7.1 Introduction 2207.2 The endocannabinoid system in the gut and in the liver 2207.3 Potential therapeutic applications of cannabinoids in the gastrointestinal tract 2217.4 Potential therapeutic applications of cannabinoids in the liver 2347.5 Conclusions 2457.6 References 2468 Fifty years of ‘cannabinoid research’ and the need for a new nomenclature 261Vincenzo Di Marzo and Luciano De Petrocellis8.1 An introduction to cannabinoid research and the ‘old’ nomenclature in this field (before the year 2000) 2628.2 ‘New’ nomenclature (after the year 2000) 2698.3 ‘Multi-target’ compounds 2808.4 Conclusions 2818.5 References 281Index 291