Cannabinoids and Sleep: Molecular, Functional and Clinical Aspects (Advances in Experimental Medicine and Biology, 1297)

Foreword
Preface
	Reference
Acknowledgments
Contents
List of Contributors
Chapter 1: Constituents of Cannabis sativa
	1.1 Introduction
	1.2 Phytocannabinoids
	1.3 Non-cannabinoid Constituents
		1.3.1 Terpenoids
		1.3.2 Phenolic Compounds
		1.3.3 Alkaloids
	1.4 Conclusions
	References
Chapter 2: Synthetic and Natural Derivatives of Cannabidiol
	2.1 Introduction
	2.2 Molecular Targets of CBD
	2.3 Metabolism and Interaction with Other Drugs
	2.4 CBD Derivatives
	2.5 Perspectives
	References
Chapter 3: Clinical Pharmacokinetics of Cannabinoids and Potential Drug-Drug Interactions
	3.1 Introduction
	3.2 Pharmacokinetics of Cannabinoids
		3.2.1 Absorption
			3.2.1.1 Inhalation/Smoking
			3.2.1.2 Oral
			3.2.1.3 Sublingual
			3.2.1.4 Buccal/Oromucosal
			3.2.1.5 Rectal
			3.2.1.6 Transcutaneous
		3.2.2 Distribution
		3.2.3 Elimination
	3.3 Pharmacokinetic Interactions
		3.3.1 Cannabinoids-Statins
		3.3.2 Cannabinoids-Warfarin
		3.3.3 Cannabinoids-Anticonvulsants
			3.3.3.1 With Clobazam, Clonazepam
			3.3.3.2 With Valproic Acid
		3.3.4 Cannabinoids and Substrates of Efflux Transporters
		3.3.5 Drug Effects on Cannabinoids Levels
	3.4 Conclusions
	References
Chapter 4: Cannabinoid Receptors and Ligands: Lessons from CNS Disorders and the Quest for Novel Treatment Venues
	4.1 Introduction
	4.2 Cannabinoid Receptors, CB1Rs and CB2Rs
	4.3 The Endocannabinoid System in the Cells of the CNS
	4.4 General Downstream Signaling Mediated by CB1Rs and CB2Rs
	4.5 The Endocannabinoid System and CNS Disorders: Traumatic Brain Injury, Multiple Sclerosis, Alzheimer´s Disease, Parkinson´s...
		4.5.1 Cannabinoids and Traumatic Brain Injury
	4.6 Cannabinoids and Multiple Sclerosis
	4.7 Cannabinoids and Alzheimer´s Disease
	4.8 Cannabinoids and Parkinson´s Disease
	4.9 Cannabinoids and Epilepsy
	4.10 Cannabinoids and Autism Spectrum Disorder
	4.11 Conclusion
	References
Chapter 5: Sleep-Wake Neurobiology
	5.1 Introduction
	5.2 Characteristics of Sleep and Wakefulness States
	5.3 Mechanisms of Sleep and Wakefulness
		5.3.1 Circadian and Homeostatic Regulation of Sleep and Wakefulness
		5.3.2 Local Sleep
		5.3.3 Brain Regions and Circuits Regulating Wakefulness
			5.3.3.1 Monoaminergic Neurons
			5.3.3.2 Cholinergic Neurons in the Brain Stem and Basal Forebrain
			5.3.3.3 GABA in the Pons, Basal Forebrain and Lateral Hypothalamus
			5.3.3.4 Hypocretins (Orexins)
		5.3.4 Brain Regions and Circuits Regulating Sleep
			5.3.4.1 The Preoptic Region
			5.3.4.2 Melanin-Concentrating Hormone
			5.3.4.3 Mesopontine Reticular Formation
			5.3.4.4 Medullary Reticular Formation
	5.4 Conclusions
	References
Chapter 6: Cannabinoids and Sleep/Wake Control
	6.1 Introduction
	6.2 The Endocannabinoid System
	6.3 Cannabinoid Receptor 1 (CB1R)
	6.4 Cannabinoid Receptor 2 (CB2R)
	6.5 Other Receptors
	6.6 Cannabinoids and Sleep
	6.7 Cannabinoid System Diurnal Variations
	6.8 Cannabinoids and Insomnia
	6.9 Therapeutic Potential
	6.10 Discussion and Conclusions
	References
Chapter 7: Effects of Cannabinoid Agonists and Antagonists on Sleep in Laboratory Animals
	7.1 Introduction
	7.2 Before the Discovery of Cannabinoid Receptors
		7.2.1 Exogenous Cannabinoids
	7.3 After the Discovery of Cannabinoid Receptors
		7.3.1 Exogenous Cannabinoid Agonists
		7.3.2 Endogenous Cannabinoid Agonists
	7.4 Antagonists/Inverse Agonists of Cannabinoid Receptors
	7.5 Allosteric Modulation
	7.6 Effect of Cannabinoid Receptors on Sleep
	7.7 Conclusion
	References
Chapter 8: Modulation of Noradrenergic and Serotonergic Systems by Cannabinoids: Electrophysiological, Neurochemical and Behav...
	8.1 Introduction
	8.2 Modulation of Locus Coeruleus/Noradrenergic System by Cannabinoids
		8.2.1 The Locus Coeruleus: Anatomy, Physiology, and Role in the Sleep/Wake Cycle
		8.2.2 Distribution of the Endocannabinoid System in the Locus Coeruleus/Noradrenergic System
		8.2.3 In Vivo Evidence for Interactions Between the Locus Coeruleus/Noradrenergic and Endocannabinoid Systems
			8.2.3.1 Electrophysiological Findings
			8.2.3.2 Neurochemical Findings
			8.2.3.3 Behavioral Findings
		8.2.4 In Vitro Evidence for Interactions Between the Locus Coeruleus/Noradrenergic and Endocannabinoid Systems
			8.2.4.1 Electrophysiological Data
			8.2.4.2 Neurochemical Data
		8.2.5 Concluding Remarks
	8.3 Modulation of Dorsal Raphe Nucleus/Serotonergic Systems by Cannabinoids
		8.3.1 The Dorsal Raphe Nucleus: Anatomy, Physiology, and Role in Sleep/Wake Cycle
		8.3.2 Distribution of the Cannabinoid System in the Dorsal Raphe Nucleus/Serotonergic System
		8.3.3 In Vivo Evidence for Interactions Between the Dorsal Raphe Nucleus/Serotonergic and Endocannabinoid Systems
			8.3.3.1 Electrophysiological Findings
			8.3.3.2 Neurochemical Results
			8.3.3.3 Behavioral Findings
		8.3.4 In Vitro Evidence for Interactions Between the Dorsal Raphe Nucleus/Serotonergic and Endocannabinoid Systems
		8.3.5 Concluding Remarks
	8.4 General Conclusions
	References
Chapter 9: Natural Cannabinoids as Templates for Sleep Disturbances Treatments
	9.1 Introduction
	9.2 The Neurobiology of Sleep
	9.3 Molecular Components of Cannabis sativa
	9.4 The Sleep-Wake Cycle Under the Influence of Cannabidiol
	9.5 The Putative Therapeutic Use of Cannabidiol on Sleep Disturbances
	9.6 Conclusions and Future Directions
	References
Chapter 10: The Effect of Cannabinoids on the Brain´s Circadian Clock
	10.1 Introduction
	10.2 Cannabinoid Receptors in the SCN
	10.3 Cellular and Network Actions of Cannabinoids Within the SCN
	10.4 Cannabinoid Actions on Circadian Rhythms and Entrainment
	10.5 Conclusion
	References
Chapter 11: Effects of Cannabis Consumption on Sleep
	11.1 Introduction
	11.2 Cannabis Compounds
	11.3 Sleep-Wake Cycle
	11.4 Effects of Cannabis on Human Sleep
	11.5 Cannabis and Human EEG Activity
	11.6 Murine Experimental Models for Studying the Effect of Cannabis on Sleep
		11.6.1 Quantitative Analysis of the EEG Activity During Sleep and Wakefulness in Rodents
		11.6.2 Effect of Vaporized Cannabis on Sleep and Electrocortical Activity in Rats
		11.6.3 Effect of Vaporized Cannabis on Electrocortical Activity in Rats
			11.6.3.1 Light Phase
			11.6.3.2 Dark Phase
			11.6.3.3 Day vs. Night Effects of Cannabis
		11.6.4 Conclusions and Future Directions
	References
Chapter 12: Addiction and Sleep Disorders
	12.1 Shared Neuroanatomy
	12.2 Shared Neurotransmitters
	12.3 Focus on Orexin
	12.4 Cycles Intertwined
	12.5 Specific Substances of Abuse
	12.6 Focus on Cannabis
	12.7 Cannabis and Sleep Disorders
	12.8 Cannabis Withdrawal and Sleep
	12.9 Cannabis Relapse and Sleep
	12.10 Clinical Considerations
	12.11 Conclusion
	References
Chapter 13: Cannabis for Restless Legs Syndrome
	13.1 Introduction
	13.2 Definition
	13.3 Epidemiology
	13.4 Pathophysiology
	13.5 Treatment
	13.6 Cannabis in RLS
	13.7 Putative Mechanism of Action of Cannabis on RLS
	13.8 Conclusion
	References
Correction to: Modulation of Noradrenergic and Serotonergic Systems by Cannabinoids: Electrophysiological, Neurochemical and B...
	Correction to: Chapter 8 in: J. M. Monti et al. (eds.), Cannabinoids and Sleep, Advances in Experimental Medicine and Biology ...