Cannabinoids and Neuropsychiatric Disorders (Advances in Experimental Medicine and Biology Book 1264)

"This volume highlights the recent advances in the understanding of the endocannabinoid system and the likely benefit from the therapeutic effects of cannabinoid treatment in a variety of health issues. Archeological evidence has shown that Cannabis has a long history of use for multiple purposes, including the treatment of medical conditions. The primary active constituent of the hemp plant Cannabis sativa, delta 9-tetrahydrocannabinol (Δ9-THC), causes euphoria, enhancement of sensory perception, tachycardia, antinociception, difficulties in concentration and impairment of memory, among other effects. Despite these undesirable effects, signaling is mostly inhibitory and suggests a putative role for cannabinoids as therapeutic agents by managing several diseases where inhibition of neurotransmitter release would be beneficial. The themes of this book have been edited and written by world-leaders in the field, The contents of the volume aims at readers from a range of academic and professional disciplines, such as biomedicine, several areas of biology, neurology, clinical medicine and pharmacy." -- Provided by the publisher Foreword 8 Preface 11 Reference 11 Reference 11 Acknowledgments 12 Contents 14 1: Constituents of Cannabis Sativa 15 1.1 Introduction 15 1.2 Constituents of Cannabis sativa 16 1.2.1 Cannabinoids 16 1.2.1.1 THC-Type Cannabinoids 16 Delta9-THC 16 Delta8-THC 17 Synthetic Delta9-THC 17 Delta9-THC-Acid (THCA) 17 Tetrahydrocannabivarin 18 1.2.1.2 Cannabidiol-Type Cannabinoids 18 Cannabidiol 18 Cannabidiolic Acid 19 Cannabidivarin 20 Cannabigerol 20 1.2.2 Terpenes 20 1.2.2.1 D-Limonene 21 1.2.2.2 β-Myrcene 21 1.2.2.3 α-Pinene 21 1.2.2.4 β-Caryophyllene 21 1.2.3 Conclusions 21 References 22 Chapter 2: Neuromolecular Mechanisms of Cannabis Action 28 2.1 Introduction and Scope of this Chapter 28 2.1.1 Neuromolecular Targets of THC: The Cannabinoid Receptors 29 2.1.1.1 CB1 Cannabinoid Receptor Characterisation: Protein, Distribution, Signalling and Pharmacology 29 2.1.1.2 CB2 Cannabinoid Receptor Characterisation: Protein, Distribution, Signalling and Pharmacology 31 2.1.2 Neuromolecular Targets of THC: Beyond the Cannabinoid Receptors 32 2.1.3 Neuromolecular Targets of CBD 33 2.1.4 Neuromolecular Targets of Other Cannabinoids 34 2.1.4.1 Delta9-Tetrahydrocannabidivarin 34 2.1.4.2 Cannabinol 34 2.1.4.3 Delta9-Tetrahydrocannabinolic Acid 34 2.1.4.4 Cannabidivarin 35 2.1.4.5 Cannabidiolic Acid 35 2.1.4.6 Cannabigerol 35 2.1.4.7 Cannabichromene 35 2.1.5 Concluding Remarks 35 References 36 Chapter 3: Neuropharmacological Effects of the Main Phytocannabinoids: A Narrative Review 42 3.1 Introduction 42 3.2 Neuromolecular mechanisms of action of the main phytocannabinoids 44 3.2.1 THC 44 3.2.2 CBD 45 3.2.3 Delta-9-THCV 45 3.2.4 Delta-9-THCA 47 3.2.5 Delta-8-THC 47 3.2.6 CBDV 47 3.2.7 CBN 47 3.2.8 CBG 47 3.2.9 CBC 47 3.2.10 CBDA 48 3.3 Neurochemical and behavioral effects of THC and CBD: Human studies 48 3.3.1 THC 48 3.3.2 CBD 50 3.4 Approved indications of cannabis-based products, THC and CBD 51 3.4.1 Cannabis-based products 51 3.4.2 THC 51 3.4.2.1 Nausea and vomiting due to chemotherapy 51 3.4.2.2 Appetite and decreasing weight loss associated with HIV/AIDS 52 3.4.2.3 Multiple sclerosis symptoms (spasticity and chronic pain) 52 3.4.2.4 Chronic pain (neuropathic and cancer pain) 53 3.4.3 CBD 53 3.4.3.1 Antiepileptic 53 3.4.3.2 Therapeutic potentials of CBD with moderate/modest evidence from RCTs 53 3.5 Adverse effects of THC and CBD 53 3.5.1 Cannabis-based products and THC 53 3.5.2 CBD 54 3.6 Conclusions 55 References 56 Chapter 4: Emerging Roles of Cannabinoids and Synthetic Cannabinoids in Clinical Experimental Models 59 4.1 Introduction 59 4.1.1 Cannabinoid Classifications 60 4.2 Endocannabinoids 60 4.3 Phytocannabinoids 60 4.4 Synthetic Cannabinoids 61 4.5 Cannabinoids in Neuromodulation 62 4.5.1 Cannabinoids in Epilepsy 63 4.5.2 Cannabinoids in Alzheimer ́s Disease 64 4.5.3 Cannabinoids in Parkinson ́s Disease 66 4.6 Cannabinoids in Cancer 67 4.7 Cannabinoids in Metabolic Disorders 68 4.8 Conclusions 69 References 71 Chapter 5: Cannabis and Depression 78 5.1 Introduction 78 5.2 Co-Occurrence of Cannabis Use and Depression 79 5.2.1 Cannabis Use among Individuals with Depression 79 5.2.2 Depression among Cannabis Users 80 5.3 Cannabis Use and Depression: Longitudinal Evidence 80 5.4 Cannabis Use and Depression: Contributing Factors 81 5.4.1 Age and Gender as Possible Moderators of the Association between Cannabis Use and Depression 81 5.5 The Effect of Cannabis Use on the Course of Depression 82 5.5.1 The Effect on Natural Outcome of Depression: Population-Based Studies 82 5.5.2 Genetics and the Neurological Basis of the Association between Cannabis Use and Depression 84 5.5.2.1 Genetic Studies on CUD 84 5.5.2.2 Specific Genetic Studies on the Association between Cannabis Use and Depression 84 5.5.3 The Use of Medical Cannabis for Treating Depression 85 5.5.3.1 Pre-Clinical Studies on Cannabis as an Anti-Depressant 85 5.5.3.2 Clinical Studies on Cannabis as an Anti-Depressant 86 5.5.4 Discussion 86 5.6 Pharmacological Treatment for Individuals with Comorbid Depression and CUD 86 5.6.1 Pharmacological Treatment for CUD 86 5.6.2 Treatment of Patients with Comorbidity of Cannabis Dependence and Depression 87 5.7 Summary 87 References 88 Chapter 6: Recent Advances in the Potential of Cannabinoids for Neuroprotection in Alzheimer ́s, Parkinson ́s, and Huntington ́s ... 92 6.1 Introduction 93 6.2 Receptors that Respond to Cannabinoids 94 6.3 Addressing Neuroprotection in Humans 94 6.4 Potential of Cannabinoids in Parkinson ́s Disease 95 6.5 Potential of Cannabinoids in Alzheimer ́s Disease 96 6.6 Potential of Cannabinoids in Huntington ́s Disease 98 References 99 Chapter 7: Cannabidiol Therapy for Refractory Epilepsy and Seizure Disorders 104 7.1 Introduction 104 7.2 Pharmacology of Cannabinoids 105 7.3 Mechanism, Bioavailability, and Metabolism of THC 106 7.4 Mechanism, Bioavailability, and Metabolism OF CBD 107 7.5 Translational Studies of CBD on the Comorbities of Epilepsy 108 7.5.1 Neuroprotective Actions of CBD 108 7.5.2 Anti-inflammatory Actions of CBD 109 7.5.3 CBD Facilitation of Neurogenesis 110 7.5.4 Anxiolytic Actions of CBD 110 7.6 Pivotal Clinical Trials That Led to the Approval of Epidiolex 111 7.7 Adverse Effects and Drug Interactions 114 7.8 Conclusions and Future Perspectives 115 References 117 Chapter 8: Cannabinoid-Based Medicines and Multiple Sclerosis 122 8.1 Introduction 122 8.2 Medicinal Cannabinoids 124 8.2.1 Dronabinol 125 8.2.2 Nabilone 127 8.2.3 Nabiximols 128 8.3 Endocannabinoid System Modulators 129 8.3.1 CB1R and CB2R Ligands 129 8.3.2 Inhibitors of Metabolic Enzymes of Endocannabinoids 133 8.4 Conclusions 136 References 137 Chapter 9: Psychiatric Disorders and Cannabinoid Receptors 141 9.1 Introduction 142 9.2 Endocannabinoid Signaling in Psychiatric Disorders 143 9.3 ECS Modulation of Neuro-Immune-Microbiome Cross Talk in Psychiatric Disorders 144 9.4 Cannabinoid Receptors in Psychiatric and Neurological Disorders 146 9.4.1 Role of CBRs in Anxiety-Related Disorders 147 9.4.2 Role of CBRs in Depression 148 9.4.2.1 Role of CBRs in the Antidepressant Action of Ketamine 149 9.4.3 Role of CBRs in Schizophrenia 150 9.4.4 Role of CBRs Addictive Disorders 151 9.4.5 Role of CBRs in Other Psychiatric Disorders: Autism Spectrum Disorders (ASDs) and Attention Deficit Hyperactivity Disord... 152 9.5 CBRs and Comorbidity between Psychiatric Disorders and Neurological Disturbances 153 9.6 CBR Polymorphisms and Epigenetic Mechanisms in Psychiatric Disorders 154 9.7 Emerging Trends in Targeting CBRs in Psychiatric and Neurological Disorders 156 9.8 Current State of Evidence on the Health Effects of Cannabis and Cannabinoids 158 9.9 Concluding Remarks 159 References 160