Chapter
3.1. Sample Storage, Tissue Homogenization, Internal Standards, Protein Precipitation, and Lipid Extraction Technique
3.2. Purification of the Extracts
3.3. Mass Spectrometric Analysis Coupled to GC or LC
4. Advances in Expanding the Coverage of the Endocannabinoidome Using “Endocannabinoidomics“
4.1. Lipid Extraction Technique
4.3. LC-MS-IT-TOF Analysis
5. Measuring eCBs Drove Discovery of Lipoamines and Additional Mono Acylglyerols
5.1. NAEs and Other N-Acyl Amines
5.3. Products of the Oxidative Metabolism of eCBs and Related Lipids
5.4. Fatty Acid Esters of Hydroxyl Fatty Acids
Chapter Two: Endocannabinoid Turnover
2. Biosynthesis of AEA and Related N-Acylethanolamine
3. Diacylglycerol Lipase-Dependent Synthesis of 2-AG
4. 2-AG, AA, and AEA Levels in DAGL Knockout Mice
5. Pharmacological Inhibition of the DAGLs Mimics the Knockout Results
6. DAGL-Dependent Endocannabinoid Signaling Regulates Synaptic Function
7. Release and Reuptake of Endocannabinoids
8. Enzymatic Hydrolysis of AEA and Related NAEs
9. Enzymatic Hydrolysis of 2-AG and Related Monoacylglycerols
10. Pharmacological Inhibitors of Monoacylglycerol Hydrolase Activities
11. Oxidative Metabolism of Endocannabinoids
12. Integrating the Catabolism of the Endocannabinoids and Related NAEs in Health and Disease
Chapter Three: Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads
2. Cannabis Phytocannabinoids (Fig. 2)
2.1. Tetrahydrocannabinol
2.1.1. THC Mechanisms at CB1 and CB2
2.1.2. THC Activity Independent of CB1 and CB2
2.1.3. Receptors and Channels
2.6. Tetrahydrocannabivarin
2.7. Tetrahydrocannabinolic Acid
2.10. Cannabigerol Monomethyl Ether
4. Cannabis Monoterpenoids (Fig. 3)
4.17. 1,8-Cineole (Eucalyptol)
5. Cannabis Sesquiterpenoids (Fig. 4)
5.3. Humulene (α-Caryophyllene)
6. Cannabis Odds and Ends: Root Triterpenoids and Alkaloids, Leaf Flavonoids, Seed Coats, and Sprouts (Fig. 5)
6.3. Cannabis Root Alkaloids: Cannabisativine and Anhydrocannabisativine
6.4. Other Root Components
6.7. Cannabis Bibenzyl Compounds
Chapter Four: Spicing Up Pharmacology: A Review of Synthetic Cannabinoids From Structure to Adverse Events
1. The Cannabinoid System, Phytocannabinoids, Endocannabinoids, and Synthetic Cannabinoids
2. Signaling Pathways Associated to SCB
3. Structural Classification of SCB
4. Cannabinoid/CB1 Receptors Involvement in Memory Regulation and Psychosis
4.1. CB1 Receptor Role in the Regulation of Memory and the Effects of Exogenous Cannabinoids
4.2. Cannabinoids and Dorsal Striatal Memory
4.3. Cognitive Changes in SCB Users
4.4. Role of CB1 Receptors in Psychosis
5. Clinical Adverse Effects of SCB
5.1. Adverse Cardiovascular Effects
5.2. Adverse Pulmonary Effects of SCB
5.3. Acute Kidney Injury From SCB
5.4. Adverse Neurological Effects of SCB: Psychosis and Catatonia
5.5. Adverse Neurological Effects of SCB: Seizures, Epilepsy, and Tremor
5.6. SCB Withdrawal Effects
5.7. SCB-Associated Deaths
5.8. Potential Therapeutic Use of SCB
Chapter Five: CB1 and CB2 Receptor Pharmacology
2. Pharmacological Characterization
3. Natural Polymorphisms and Alternative Splice Variants
6. Cannabinoid Receptor Signaling Pathways Associated With Differentiated Tissues
6.1. Signaling in Smooth Muscle Cells
6.1.2. Vascular Arterioles
6.1.3. Gastric Smooth Muscle
6.2. Signaling in Metabolic Regulation and Disease
6.2.1. Liver Development and Function
6.2.3. Liver Stellate Cells, Myofibroblasts, and Bile Duct Epithelial Cholangiocytes
6.3. Cannabinoid Receptor Signaling in Neuronal Cells
6.3.1. CB1 Receptor Regulation of Focal Adhesion Kinase and Integrin Signaling for Actin Cytoskeleton Organization and Ce ...
6.3.2. CB1 Receptor Regulation of Gene Expression in Neurite Elongation
7. Extended Agonist Exposure
8. Agonist-Biased Signaling: Targeting Receptor Conformations Leading to Selective Pharmacological Responses
8.1. Functional Selectivity in CB1 or CB2 Receptor Signaling
Chapter Six: Functional Selectivity at Cannabinoid Receptors
2. Why Does Functional Selectivity Matter?
3. Determination of Functional Selectivity
4. Functional Selectivity at Cannabinoid Receptors
4.1. Downstream Signaling via Cannabinoid Receptors
5. Cannabinoid Receptor Agonist-Selective Signaling
6. Functional Selectivity in Complex Systems
7. Mechanisms of Functional Selectivity
Chapter Seven: Cannabinoid Receptor-Related Orphan G Protein-Coupled Receptors
2. Evidence for Novel Cannabinoid Receptor-Like GPCR Targets
3. GPR18 as a Cannabinoid Receptor-Like GPCR
3.1. Distribution of GPR18
3.2. Pathophysiology of GPR18
3.3. Endogenous Ligand Activity at Recombinant GPR18
3.4. N-Arachidonoylglycine
3.5. Pharmacology of Synthetic Ligands at GPR18
4. GPR55 as a Cannabinoid Receptor-Like GPCR
4.1.1. Endogenous Lipids and GPR55
4.1.2. Synthetic GPR55 Ligands
4.1.3. Phytocannabinoids as GPR55 Ligands?
4.2. Downstream Signaling in Heterologous Expression Systems and Native Cells
4.3. Native Expression of GPR55
4.4. Exploring the (Patho)physiology of GPR55
5. GPR119 as a Cannabinoid Receptor-Like GPCR
5.1. Pathophysiology of GPR119
5.2. Endogenous Ligand Activity at Recombinant GPR119
5.3. N-Oleoylethanolamine
5.4. Pharmacology of Synthetic Ligands at GPR119
Chapter Eight: Actions and Regulation of Ionotropic Cannabinoid Receptors
2. TRPV Channels and Cannabinoid-Mediated Regulation
3. TRPA Channels and Cannabinoid-Mediated Regulation
4. TRPM Channels and Cannabinoid-Mediated Regulation
5. TRPC Channels and Cannabinoid-Mediated Regulation
6. Non-TRP Ion Channels and Cannabinoid-Mediated Regulation
Chapter Nine: The Role of Nuclear Hormone Receptors in Cannabinoid Function
2.1. PPARα Receptor Structure and Function
2.2. Role in PPARα in Disease
2.3. In Vitro Evidence of Cannabinoid Activation of PPARα
2.3.1. Transcriptional, Binding, and Knockdown Studies
2.3.2. In Vitro Cannabinoid Responses Mediated by PPARα
2.4. In Vivo Evidence of Cannabinoid Activation of PPARα
2.4.1. In Vivo Antagonist Studies
3.1. PPARγ Receptor Structure and Function
3.2. Role in PPARγ in Disease
3.3. In Vitro Evidence of Cannabinoid Activation of PPARγ
3.3.1. Transcriptional and Binding Studies
3.3.2. Cellular/Tissue Responses of Cannabinoids Mediated by PPARγ
3.4. In Vivo Evidence of Cannabinoid Activation of PPARγ
4.1. PPARβ/δ Receptor Structure and Function
4.2. Role in PPARβ/δ in Disease
4.3. Evidence of Cannabinoid Activation of PPARβ/δ
5. Modulation of the Endocannabinoid System and PPAR Activation
6. Other Nuclear Hormone Receptors
Chapter Ten: Cannabinoids in the Cardiovascular System
2. Cardiovascular Effects of Cannabinoids
2.1. In Vivo Effects of Endocannabinoids
2.2. Local Vascular Tone Regulation
3. Endocannabinoid Metabolites
4. Endocannabinoid Congeners
5. Targeting the ECS in Cardiovascular Diseases
5.1. Therapeutic Potential of CB1 Antagonists
5.2. Therapeutic Potential of FAAH/MGL Inhibitors
5.3. Therapeutic Potential of CB2R Agonists
6. Clinical Trials of CB1R Antagonists, CB2R Agonists and FAAH Inhibitors
Chapter Eleven: Is the Cannabinoid CB2 Receptor a Major Regulator of the Neuroinflammatory Axis of the Neurovascular Unit ...
1.1. The Endocannabinoid System in Brief
1.3. CB2 Expression in the Peripheral Immune System
2.1. Key BBB Junctional Structures
2.2. Transport Across the BBB
3. Evidence for the Expression of CB2 by the NVU and BBB
4. Evidence of the Regulation of NVU Functions by Cannabinoids
Chapter Twelve: Cannabinoids as Anticancer Drugs
2. Modulation of the Endocannabinoid System in Tumor Progression
2.1. Regulation of Endocannabinoids in Cancer Tissue
2.2. FAAH and MAGL Expression in Cancerous Lesions
2.3. Cannabinoid Receptor Expression in Cancerous Lesions
3. The Role of the Endocannabinoid System in Cancer Progression and Potential Pharmacological Options of Cannabinoid Comp ...
3.1. Cannabinoids as Anticancer Drugs
3.2. Effects of Cannabinoids on Tumor Angiogenesis
3.2.1. In Vivo Effects of Cannabinoids on Tumor Angiogenesis
3.2.2. Inhibition of Angiogenic Capacities of Endothelial Cells by Cannabinoids
3.2.3. Suppression of Tumor Angiogenesis by Cannabinoid-Modulated Intercellular Cross Talks
3.3. Effects of Cannabinoids on Metastasis
4. Inhibition of Endocannabinoid-Degrading Enzymes as Anticancer Strategy
Chapter Thirteen: Cannabinoids and Pain: Sites and Mechanisms of Action
2. Anatomical Localization of the Endocannabinoid System Throughout the Pain Pathway
3. Supraspinal Sites and Mechanisms of Action
3.1. Evidence From Acute Pain Models
3.2. Evidence From Inflammatory Pain Models
3.3. Evidence From Neuropathic Pain Models
4. Spinal Sites and Mechanisms of Action
4.1. Evidence From Acute Pain Models
4.2. Evidence From Inflammatory Pain Models
4.3. Evidence From Neuropathic Pain Models
5. Peripheral Sites and Mechanisms of Action
5.1. Evidence From Acute Pain Models
5.2. Evidence From Inflammatory Pain Models
5.3. Evidence From Neuropathic Pain Models
Cannabinoid Pharmacology
( Volume 80 )
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