Cannabinoids by Marzo, Vincenzo Di -- Read -- Imperial Library of Trantor

Index

Cover Title Parge Copyright Contents List of Contributors Preface Chapter 1 Looking ahead after 50 years of research on cannabinoids

1.1 Summary 1.2 Introduction 1.3 Cannabidiol (CBD) 1.4 Fatty acid amides of amino acids and related compounds 1.5 Conclusions 1.6 References

Chapter 2 Cannabinoid receptor intracellular signalling: The long journey from binding sites to biological effects

2.1 Historical progression: Serendipity to opportunity 2.2 Significance of being a G protein coupled receptor (GPCR)

2.2.1 Cannabinoid receptor-mediated inhibition of cyclic AMP production 2.2.2 Cannabinoid regulation of other effectors including phospholipases C (PLC) and A (PLA)

2.3 CB1 cannabinoid receptor interactions with other cellular signals

2.3.1 Mitogen activated protein kinases (MAPKs)

2.4 Functional role of CB1 receptor accessory proteins

2.4.1 CB1 receptor association with GRKs and β-arrestins 2.4.2 Regulation of CB1 receptor lysosomal sorting: Emerging toles for AP-3 and GASP1 2.4.3 Cannabinoid receptor interacting proteins (CRIP1a and b)

2.5 Opportunities: Pharmacotherapeutic insights based on cell signalling

2.5.1 Specialised cell signalling: Neurodevelopment and neuroprotection 2.5.2 From small lipid ligands to interacting and accessory proteins to therapeutic peptides

2.6 Concluding remarks 2.7 References

Chapter 3 Endocannabinoid biochemistry: What do we know after 50 years?

3.1 Introduction 3.2 Endocannabinoids and related molecules

3.2.1 Anandamide and 2-arachidonoylglycerol 3.2.2 Additional cannabinoid receptor ligands 3.2.3 Congeners of endocannabinoids

3.3 Biosynthesis of endocannabinoids and related molecules

3.3.1 Biosynthesis of AEA and congeners 3.3.2 Biosynthesis of 2-AG

3.4 Degradation of endocannabinoids

3.4.1 Transport across the plasma membrane 3.4.2 Adiposomes and intracellular transporters of endocannabinoids 3.4.3 Degradation of AEA and congeners 3.4.4 Degradation of 2-AG

3.5 Oxidative metabolism of endocannabinoids 3.6 Conclusions and future perspectives 3.7 References

Chapter 4 Genetic dissection of the endocannabinoid system and how it changed our knowledge of cannabinoid pharmacology and mammalian physiology

4.1 Introduction: To set the stage 4.2 Tool box for genetic dissection

4.2.1 Available tools 4.2.2 Generation of mutant mouse lines 4.2.3 Generation of viral transgenes

4.3 Understanding cannabinoid pharmacology

4.3.1 ‘Tetrad’ effects 4.3.2 Bimodal action of cannabinoid pharmacology 4.3.3 Memory performance and cognition 4.3.4 Effects on neuronal network activity 4.3.5 Anti-depressant-like effects 4.3.6 Multiple sclerosis 4.3.7 Analgesia 4.3.8 Inflammatory side-effects 4.3.9 Dysphoric effects 4.3.10 Downstream signalling

4.4 Unravelling endocannabinoid system functions

4.4.1 Endocannabinoids 4.4.2 Specificity of the endocannabinoid synthesising and degrading machinery 4.4.3 Physiological functions of the endocannabinoid system

4.5 Caveats in genetics 4.6 What have we learnt about cannabinoid pharmacology and mammalian physiology? 4.7 Perspectives 4.8 References

Chapter 5 Cannabinoids, endocannabinoids and stress

5.1 Introduction

5.1.1 Consequences of stress exposure 5.1.2 Cannabis sativa, Δ9-tetrahydrocannabinol (THC), and cannabinoid receptors 5.1.3 Endocannabinoid regulation of synaptic activity 5.1.4 Stress and the cannabinoids

5.2 Regulation of endocannabinoid signalling by stress

5.2.1 Rapid time domain effects: Glucocorticoids recruit CNS ECS as a mechanism to regulate synaptic plasticity 5.2.2 Slow time domain effects: Glucocorticoid and stress regulation of CNS CB1R expression 5.2.3 Chronic stress and ECS 5.2.4 Glucocorticoid and stress regulation of FAAH and MAGL expression 5.2.5 Summary

5.3 ECS regulation of the HPA axis response to stress

5.3.1 ECS and basal glucocorticoid concentrations 5.3.2 Does ECS regulate initiation of HPA axis activation by stress? 5.3.3 ECS participates in feedback regulation of the HPA axis by CORT 5.3.4 Changes in ECS contribute to habituation of HPA axis responses to stress 5.3.5 Pituitary and adrenal ECS 5.3.6 Summary

5.4 ECS role in SNS responses to stress 5.5 Stress and ECS in the periphery 5.6 Summary 5.7 References

Chapter 6 Cannabinoids and the brain: New hopes for new therapies

6.1 Cannabinoids and the brain: A long journey together

6.1.1 Functions of the endocannabinoid signalling system in the brain 6.1.2 Retrograde signalling by endocannabinoids and their receptorsin excitatory and inhibitory synapses 6.1.3 The role of the endocannabinoid signalling in glial cells

6.2 Brain processes and brain disorders investigated in relation to the endocannabinoid system

6.2.1 Disorders affecting motor performance or coordination 6.2.2 Pain-related disorders 6.2.3 Hyperexcitability disorders 6.2.4 Disorders related to memory impairment 6.2.5 Psychiatric disorders 6.2.6 Addictive disorders 6.2.7 Sleep disorders 6.2.8 Nausea and vomiting 6.2.9 Feeding disorders 6.2.10 Neurodegenerative disorders 6.2.11 Brain tumours

6.3 Concluding remarks and future perspectives 6.4 References

Chapter 7 Potential therapeutic applications of cannabinoids in gastrointestinal and liver diseases: Focus on Δ9-tetrahydrocannabinol pharmacology

7.1 Introduction 7.2 The endocannabinoid system in the gut and in the liver 7.3 Potential therapeutic applications of cannabinoids in the gastrointestinal tract

7.3.1 Gastrointestinal reflux disease (GERD) 7.3.2 Irritable bowel syndrome (IBS) 7.3.3 Inflammatory bowel disease (IBD) 7.3.4 Colon cancer

7.4 Potential therapeutic applications of cannabinoids in the liver

7.4.1 Non-alcoholic fatty liver disease (NAFLD) 7.4.2 Alcoholic liver disease (ALD) 7.4.3 Chronic viral hepatitis C 7.4.4 Liver fibrosis 7.4.5 Liver cirrhosis 7.4.6 Portal hypertension 7.4.7 Hyperdynamic circulatory syndrome 7.4.8 Ascites 7.4.9 Cirrhotic cardiomyopathy 7.4.10 Susceptibility to bacterial infections 7.4.11 Hepatic encephalopathy 7.4.12 Acute liver injury 7.4.13 Hepatocellular carcinoma and cholangiocarcinoma

7.5 Conclusions 7.6 References

Chapter 8 Fifty years of 'cannabinoid research' and the need for a new nomenclature

8.1 An introduction to cannabinoid research and the 'old' nomenclature in this field (before the year 2000)

8.1.1 'Cannabinoids’ 8.1.2 'Cannabimimetic’ activity 8.1.3 'Cannabinoid receptors’ 8.1.4 ‘Endocannabinoids’ and ‘endocannabinoid receptors’ 8.1.5 ‘Endocannabinoid metabolic enzymes’ and the ‘endocannabinoidsystem’

8.2 'New' nomenclature (after the year 2000) 8.2.1 ‘Endocannabinoid-related mediators’ and the‘endocannabinoidome’ 8.3 'Multi-target' compounds 8.4 Conclusions 8.5 References

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