Endocannabinoids: The Brain and Body's Marijuana and Beyond

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ISBN: 9780415300087 | 0415300088
Cover: Hardcover
Copyright: 11/1/2005

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This volume explores research on marijuana-like substances produced naturally by the human body and brain. These endogenous lipid molecules, or endocannabinoids, constitute a uniquely conserved and ubiquitous physiological control system in a variety of species and plays fundamental roles in development and cell death. The authors discuss this remarkable progress in marijuana research including identification of genes encoding endocannabinoid receptors, isolation of endocannabinoids and entourage ligands, and functional identification of transporters and enzymes for the biosynthesis and degradation of these endogenous substances.

Part I Historical Aspects and Chemistry

(54)

Chapter 1 Look Back in Ananda-40 Years of Research on Cannabinoids

(8)

Raphael Mechoulam

Chapter 2 The Relationship between Endocannabinoid Conformation and Endocannabinoid Interaction at the Cannabinoid Receptors

(44)

Patricia H. Reggio

Introduction

(2)

The Endocannabinoid System

(4)

Endocannabinoid Conformation as a Function of Environment

(8)

Endocannabinoid/Parent Fatty Acid, Low-Energy Conformations

(1)

Fatty Acid Nomenclature

(1)

Arachidonic Acid and Related Fatty Acids: Conformational Analysis

(1)

Csp2–Csp3 Bond Rotation

(1)

Csp3–Csp3 Bond Rotation

(1)

Calculations In Vacuo

(1)

Calculations in Nonpolar (CHCl3) vs. Polar (Aqueous) Environments

(1)

Calculations in Protein Environments

(1)

Experimental X-Ray Crystal Structures: Arachidonic Acid and Arachidonic Acid Derivatives

(2)

Experimental NMR Solution Studies of AEA and AEA Analogs

(1)

Calculations in a Lipid Environment

(1)

Biophysical Studies of Cannabinoids in a Lipid Environment

(1)

Summary

(1)

Endogenous Cannabinoid Structure–Activity Relationships

(10)

Fatty Acid Ethanolamides

(1)

CB1 SAR for Fatty Acid Ethanolamides

(1)

Head Group SAR: Fatty Acid Ethanolamides

(1)

Amido Group Modifications

(1)

Head Group SAR Summary

(1)

Acyl Chain SAR: Fatty Acid Ethanolamides

(1)

Effect of Unsaturation

(1)

Effect of Terminal Alkyl Tail Length

(1)

Effects of Branching in Acyl Chain

(1)

Effects of Conjugation in Acyl Chain

(1)

Acyl Chain SAR Summary

(1)

CB2 SAR for Fatty Acid Ethanolamides

(1)

Oleamide

(1)

SN-2-Arachidonylglycerol and Derivatives

(1)

CB1 SAR for 2-AG

(1)

CB2 SAR for 2-AG

(1)

Production of an "Entourage Effect" by Related Glycerol Derivatives

(1)

Noladin Ether

(1)

Virodhamine Endogenous Cannabinoid with Antagonist Properties at CB1 and Agonist Properties at CB2

(1)

NADA

(1)

Endocannabinoid Interaction with the Cannabinoid CB1 Receptor

(7)

The Cannabinoid Receptors

(2)

Pharmacophores for Endocannabinoid Interaction with Cannabinoid Receptors

(1)

Thomas Model

(1)

Tong Model

(1)

An Alternative Approach to Endocannabinoid Pharmacophore Construction

(1)

Endocannabinoid Interaction with CB1: Reggio Model

(3)

Acknowledgments

(1)

References

(11)

Part II Cannabinoid Receptor Genetics and Signal Transduction

(120)

Chapter 3 Endocannabinoid Receptor Genetics and Marijuana Use

(62)

Emmanuel S. Onaivi, Hiroki Ishiguro, Ping Wu Zhang, Zhicheng Lin, Babatunde E. Akinshola, Claire M. Leonard, Sanika S. Chirwa, Jianping Gong, and George R. Uhl

Introduction

(4)

Biology of Endocannabinoids

(14)

Biology of Cannabinoid Signaling

(1)

Neurobehavioral and In Vitro Actions of Cannabinoids

(3)

Interaction between the Cannabinoid and Vanilloid Systems

(2)

Involvement of Endocannabinoids in Alcohol and Drug Abuse

(3)

Cannabinoid Receptor Gene Expression

(13)

Molecular Characteristics of Cannabinoid Receptors (CNRs)

(3)

Cannabinoid Receptor Gene Knockout Mice

(2)

Other Cannabinoid Receptor Transgenic Models

(1)

Fatty Acid Amide Hydrolase Knockout Mice

(1)

Genes Encoding Endocannabinoid Transporters

(1)

Polymorphic Structure of Cannabinoid Receptor Genes

(2)

Chromosomal Mapping of the CBR Genes

(1)

Other Cannabinoid Receptors (CBRs): Functional Evidence for the Existence of Other CBRs

(1)

Is Marijuana Use Addicting?

(5)

The Genetics of Marijuana Dependence

(2)

Human Cannabinoid Receptor Genes

(2)

Neurobiology of Endocannabinoid Modulation of Other Receptor Systems

(5)

Marijuana Use in Cell Survival, Neurogenesis, and Apoptosis

(2)

An Endocannabinoid Hypothesis of Substance Abuse

100

(2)

Implication for the Medical Use of Marijuana

102

(1)

Concluding Remarks and Future Directions

103

(1)

Acknowledgments

104

(1)

References

104

(15)

Chapter 4 Endocannabinoids and Intracellular Signaling

119

(14)

Sean D. McAllister and Mary E. Abood

Introduction

119

(1)

Endocannabinoid Signaling through CB1

120

(6)

Regulation of Intracellular cAMP Levels

120

(2)

Regulation of Ion Channels

122

(1)

Inhibition of Voltage-Dependent Calcium Channels

122

(1)

Modulation of Potassium Currents

123

(1)

Modulation of Intracellular Calcium

124

(1)

Nitric Oxide

125

(1)

Regulation of Intracellular Kinases

125

(1)

Antitumor Activity

126

(1)

Endocannabinoid Signaling via CB2 Receptors

126

(1)

Regulation of Intracellular cAMP Levels

126

(1)

Modulation of Intracellular Calcium

126

(1)

Regulation of Intracellular Kinases

127

(1)

Endocannabinoid Signaling via CB, and CB2 Receptors

127

(1)

Antitumor Activity

127

(1)

Signaling Pathways in Other Cannabinoid Receptor Subtypes

127

(1)

Summary

128

(1)

References

128

(5)

Chapter 5 Endocannabinoids as Retrograde Messengers in Synaptic Transmission

133

(18)

Saori Oka, Yoshio Ishima, Keizo Waku, and Takayuki Sugiura

Introduction

133

(1)

Endocannabinoids in the Nervous System

134

(4)

Depolarization-Induced Suppression of Inhibition

138

(1)

Endocannabinoids as Retrograde Synaptic Messengers

139

(4)

Future Directions and Concluding Remarks

143

(1)

References

144

(7)

Chapter 6 Non-CB1, Non-CB2 Receptors for Endocannabinoids

151

(24)

Vincenzo Di Marzo and Luciano De Petrocellis

Introduction

151

(1)

Non-CB1, Non-CB2 Receptors for AEA

152

(3)

Evidence in Favor of the Existence of Non-CB1, Non-CB2 Receptors for AEA

152

(1)

Known GPCRs that Interact with AEA

152

(1)

Novel and As Yet Uncharacterized Non-CB1, Non-CB2 Receptors in the Brain

153

(1)

Novel and As Yet Uncharacterized Non-CB1, Non-CB2 Receptors in the Endothelium

154

(1)

Direct Interaction with Ion Channels

155

(1)

Ca²+ Channels and Ionotropic Receptors

155

(1)

Inhibition of K+ Channels

155

(1)

Endocannabinoids and Vanilloid VR1 Receptors

156

(8)

AEA and Vanilloid VR1 Receptors

156

(3)

AEA, VR1, and Cell Proliferation and Apoptosis

159

(1)

In Vivo Effects of AEA and Capsaicin: Differences and Similarities

159

(1)

Regulation of AEA Activity at VR1 Receptors

160

(3)

Other Endocannabinoids and AEA Congeners, and VR1 Receptors

163

(1)

New Receptors for AEA and 2-AG Oxidation Products

164

(2)

AEA Oxidation Products

164

(2)

2-AG Oxidation Products

166

(1)

Concluding Remarks

166

(1)

References

167

(8)

Part III Biochemistry of the Endocannabinoid System

175

(52)

Chapter 7 Occurrence, Biosynthesis, and Metabolism of Endocannabinoids

177

(38)

Takayuki Sugiura, Saori Oka, Shinobu Ikeda, and Keizo Waku

Introduction

177

(2)

Anandamide

179

(12)

Identification of Anandamide as an Endogenous Cannabinoid Receptor Ligand

179

(1)

Tissue Levels of Anandamide

180

(3)

Biosynthesis of Anandamide

183

(5)

Degradation of Anandamide

188

(1)

Oxygenation of Anandamide

189

(1)

Physiological Significance of Anandamide

190

(1)

2 Arachidonoylglycerol

191

(8)

Identification of 2-AG as an Endogenous Cannabinoid Receptor Ligand

191

(1)

Tissue Levels of 2-AG

191

(3)

Biosynthesis of 2-AG

194

(3)

Degradation of 2-AG

197

(1)

Oxygenation of 2-AG

197

(1)

Physiological Significance of 2-AG

198

(1)

Concluding Remarks

199

(1)

References

200

(15)

Chapter 8 Endocannabinoids and Eicosanoids: All in the Family

215

(12)

Sumner Burstein

Introduction

215

(1)

Biosynthesis of PGs and Leukotrienes

215

(3)

Biosynthesis of the Endocannabinoids

218

(3)

Metabolism of the Endocannabinoids

221

(1)

Interrelationships between Endocannabinoids and Eicosanoids

222

(2)

Acknowledgments

224

(1)

References

224

(3)

Part IV Endocannabinoids in CNS Physiology

227

(122)

Chapter 9 Man-Made Marijuana: Endocannabinoid Modulation of Synaptic Transmission and Implications for the Regulation of Synaptic Plasticity

229

(20)

Alexander F. Hoffman and Carl R. Lupica

Introduction

229

(1)

Synaptic Effects of Exogenous Cannabinoid Ligands

230

(2)

Cannabinoid Regulation of Synaptic GABA Release

230

(1)

Cannabinoid Regulation of Synaptic Glutamate Release

230

(2)

Endocannabinoid Inhibition of Excitatory and Inhibitory Synapses

232

(10)

DSI and DSE: A Role for Endocannabinoids in Short-Term Synaptic Plasticity

232

(1)

DSI at Hippocampal Synapses

233

(1)

Endocannabinoid-Dependent DSI and DSE at Cerebellar Synapses

234

(1)

Modulation of the Release of Endocannabinoids by Other Neurotransmitters

236

(1)

Functional Implications of DSI/DSE

237

(1)

LTD: A Role for Endocannabinoids in Long-Term Plasticity

237

(1)

LTD at Glutamatergic Synapses in the Dorsal Striatum

239

(1)

LTD of Glutamatergic Synapses in the Nucleus Accumbens

239

(1)

LTD of GABAergic Synapses: Forgetting and the Endocannabinoids

240

(1)

Functional Significance of LTD

241

(1)

Conclusions and Future Directions

242

(1)

References

243

(6)

Chapter 10 Cannabinoids and the Central Serotonergic System

249

(12)

Marisela Morales

Effects of Cannabinoids on the Central Serotonergic System

249

(2)

Maternal Exposure to Cannabinoids and Its Effects on the Serotonergic System

251

(1)

Interactions between Cannabinoids and 5-HT Receptors

251

(3)

Interactions between Cannabinoids and 5-HT2 Receptors

251

(1)

Interactions between Cannabinoids and 5-HT3 Receptors

252

(2)

Neuronal Coexpression of 5-HT3A and CB1 Transcripts

254

(1)

Participation of Serotonin on Cannabinoid Effects

255

(1)

References

256

(5)

Chapter 11 Endocannabinoids and Dopamine-Related Functions in the CNS

261

(30)

Javier Fernández-Ruiz, Rosario de Miguel, Mariluz Hernández, Maribel Cebeira, and José A. Ramos

Introduction: The Control of Neurotransmitter Activity by Endocannabinoids

261

(2)

Interactions between Cannabinoids and Dopamine at the Basal Ganglia

263

(6)

Function of the Endocannabinoid System in the Basal Ganglia

263

(1)

Involvement of Dopamine in Motor Effects of Cannabinoids

264

(2)

Therapeutic Implications of Cannabinoid–Dopamine Interactions in the Basal Ganglia

266

(1)

Hyperkinetic Disorders: Huntington's Disease

266

(1)

Hypokinetic Disorders: Parkinson's Disease

267

(1)

Other Motor-Related Disorders

268

(1)

Interactions between Cannabinoids and Dopamine at the Corticolimbic Structures

269

(6)

Function of the Endocannabinoid System in the Corticolimbic Structures

270

(1)

Involvement of Dopamine in Corticolimbic Effects of Cannabinoids

271

(1)

Therapeutic Implications of Cannabinoid–Dopamine Interactions in Corticolimbic Structures

272

(3)

Drug Addiction

273

(1)

Schizophrenia

274

(1)

Interactions between Cannabinoids and Dopamine at the Hypothalamic Level

275

(2)

Function of the Endocannabinoid System in the Neuroendocrine Hypothalamus

275

(1)

Involvement of Dopamine in Neuroendocrine Effects of Cannabinoids

276

(1)

Therapeutic Implications of Cannabinoid–Dopamine Interactions in the Hypothalamus

276

(1)

Interactions between Cannabinoids and Dopamine during Brain Development

277

(1)

Cannabinoids and Tyrosine Hydroxylase during Brain Development

277

(1)

Concluding Remarks

278

(1)

References

279

(12)

Chapter 12 Pharmacology of the Oxidative Metabolites of Endocannabinoids

291

(12)

Ruth A. Ross

Introduction

291

(1)

COX Metabolism of Endocannabinoids

292

(1)

Anandamide

292

(3)

Formation and Catabolism

292

(1)

Pharmacology

293

(2)

2-Arachidonylglycerol

295

(2)

Formation and Catabolism

295

(2)

N-Arachidonoylglycine

297

(1)

Formation and Catabolism

297

(1)

Pharmacology

297

(1)

LOX Metabolism of Endocannabinoids

297

(1)

Anandaminde

297

(2)

Formation and Catabolism

297

(1)

Pharmacology

298

(1)

2-Arachidonoylglycerol

299

(1)

Formation and Catabolism

299

(1)

Pharmacology

299

(1)

Conclusions

299

(1)

References

300

(3)

Chapter 13 Behavioral Effects of Endocannabinoids

303

(46)

Marie-Hélène Thiébot, Frédèrique Chaperon, Ester Fride, and Emmanuel S. Onaivi

Introduction

304

(1)

The Endocannabinoid Physiological Control System

305

(1)

Affective Behavior

305

(6)

Anxiety-Related Behavior

305

(2)

Schizophrenia

307

(1)

Depression

308

(1)

Aggressive Behavior

309

(2)

Appetite and Feeding Behavior

311

(3)

Motivational Processes

314

(5)

Endocannabinoids in the Reward Pathway

314

(1)

Reinforcing Effects of Cannabinoids

314

(3)

Role of Cannabinoid Receptors in Motivational Processes

317

(2)

Endocannabinoids in Alcohol-Related Behaviors

319

(1)

Endocannabinoids in the Modulation of Pain

319

(5)

Convergence between Opioid, Cannabinoid, and Vanilloid Systems in Pain Pathways

319

(2)

Role of Endocannabinoids in the Modulation of Pain

321

(1)

Centrally Mediated Analgesia

321

(1)

Spinal Analgesia

322

(1)

Peripheral Analgesia

322

(2)

Stress-Induced Analgesia

324

(1)

Cognition and Memory

324

(1)

Motor Activity

325

(5)

Modulation of Motor Activity by Endocannabinoids

325

(1)

Interactions between Endocannabinoid System and GABA, Dopamine, and Glutamate Neurotransmissions in the Basal Ganglia

326

(2)

Role of Endocannabinoids in Motor Disorders

328

(1)

Huntington's Disease

328

(1)

Parkinson's Disease

329

(1)

Multiple Sclerosis

329

(1)

Gilles de la Tourette's Syndrome

330

(1)

Future Directions

330

(1)

References

331

(18)

Part V Endocannabinoids in CNS Pathology

349

(44)

Chapter 14 Neuroprotection: Glutamate and Endocannabinoids

351

(20)

Harald S. Hansen, Gitte Petersen, and Henrik H. Hansen

Introduction

351

(1)

Glutamate and Excitotoxicity

351

(1)

Endocannabinoids and Their Formation in the Brain

352

(3)

Endocannabinoids and Neuroprotection

355

(3)

Putative Neuroprotective Effects of Other NAEs

358

(1)

Final Remarks

359

(1)

Acknowledgments

360

(1)

References

360

(11)

Chapter 15 Neuropsychiatry: Schizophrenia. Depression, and Anxiety

371

(12)

Ester Fride and Ethan Russo

Introduction

371

(1)

Historical Highpoints

372

(1)

Last 40 Years

373

(3)

Mood Disorders

376

(1)

Effects of Long-Term Cannabis Use on Cognition and Behavior

376

(1)

Biological Evidence for a Role of the Endocannabinoid–CB1 Receptor System in Neuropsychiatric Disorders

377

(1)

Conclusions

378

(1)

References

379

(4)

Chapter 16 The Role of Endocannabinoids in the Development, Progression, and Treatment of Neurodegenerative Diseases

383

(10)

Michelle Glass

Introduction

383

(1)

Multiple Sclerosis

384

(1)

Cannabinoids and Movement Disorders

385

(2)

Cannabinoids and Parkinson's Disease

386

(1)

Huntington's Disease

387

(1)

Conclusion

388

(1)

References

388

(5)

Part VI Endocannabinoids in Peripheral Organ Systems

393

(122)

Chapter 17 Endocannabinoids and Gastrointestinal Function

395

(26)

Nissar A. Darmani

Introduction

395

(1)

Established Neurotransmitters of the Gut

396

(1)

Established Emetic Neurotransmitters and More Novel Mediators of Vomiting

397

(1)

Presence of Endocannabinoids and Cannabinoid CB1 Receptors in Gut—Brain Circuits Affecting GIT Motility and Emesis

398

(1)

Endocannabinoids and GI Motility

399

(4)

In Vitro Studies on Intestinal, Longitudinal, and Circular Muscle Preparations

399

(1)

In Vitro Peristalsis Studies in Isolated Intestine

400

(1)

In Vivo Intestinal Motility Studies

401

(1)

In Vitro Isolated Gastric Tissue and In Vivo Gastric Emptying Studies

402

(1)

Possible Effects of Endocannabinoids on GI Secretions

403

(1)

Endocannabinoids in Relation to Feeding and Appetite

404

(1)

Endocannabinoids and Vomiting

405

(3)

In Vitro and In Vivo Inverse Agonist/Antagonist Effects of SR141716A Rimonabant) on GI Motility, Secretion, Feeding, and Vomiting

408

(2)

Central vs. Peripheral Components of Actions of Cannabinoid CB1 Ligands on GI Motility, Feeding, and Emesis

410

(1)

Possible Role of Endocannabinoids in GI Pathological States

411

(1)

Summary and Conclusions

412

(1)

Acknowledgments

413

(1)

References

413

(8)

Chapter 18 Endocannabinoids and the Cardiovascular System

421

(10)

Michael D. Randall

Cardiovascular Effects of Cannabinoids

421

(6)

Actions of Cannabinoids In Vitro

421

(1)

Vasorelaxation

421

(1)

Action at Vanilloid Receptors

423

(1)

Vasoconstriction

424

(1)

Vascular Cannabinoid Receptors

424

(1)

Cardiac Actions

425

(1)

Actions In Vivo

425

(1)

Endocannabinoids and Pathophysiology

426

(1)

Concluding Remarks

427

(1)

Acknowledgments

427

(1)

References

427

(4)

Chapter 19 Endocannabinoids in Inflammation and Immune Response

431

(20)

Evgeny V. Berdyshev

Introduction

431

(1)

Endocannabinoids and Inflammation

432

(2)

Endocannabinoid Effect on Immune Cell Functions

434

(7)

Endocannabinoids and Hematopoietic Cell Growth and Migration

434

(5)

Endocannabinoid Effect on Leukocyte and Lymphocyte Functional Responses

439

(2)

Regulation of Endocannabinoid Metabolism in Immune Cells

441

(3)

Conclusion and Outlook

444

(1)

Acknowledgments

445

(1)

Acronyms

445

(1)

References

445

(6)

Chapter 20 Involvement of the Endocannabinoid System in Cancer

451

(16)

Mauro Maccarrone

Introduction

451

(1)

The Endocannabinoid System

452

(1)

Endocannabinoids and Cancer

453

(6)

Therapeutic Potential of Oxidative Metabolites of AEA

459

(2)

Conclusions

461

(1)

Acknowledgments

461

(1)

Acronyms

462

(1)

References

462

(5)

Chapter 21 Endocannabinoids and Endocrine Function

467

(8)

Laura L. Murphy

Introduction

467

(1)

Neuroendocrine System

467

(2)

Pituitary Gland

469

(1)

Peripheral Endocrine Tissues

469

(1)

Gonads

469

(1)

Thyroid

470

(1)

Adrenal

470

(1)

Role of Endocannabinoids in Endocrine Function

470

(1)

References

471

(4)

Chapter 22 Endocannabinoids in Fertilization, Pregnancy, and Development

475

(40)

Herbert Schuel and Lani J. Burkman

Dedication

475

(1)

Introduction

475

(3)

Fertilization

478

(14)

Endocannabinoid Signaling Modulating Sea Urchin Sperm Fertility

479

(1)

Inhibition of Fertilization

479

(1)

Radioligand Binding

481

(1)

Receptor Characterization

482

(1)

Physiological Role for NAE Signaling during Fertilization

482

(3)

Endocannabinoid Signaling in the Modulation of Human Sperm

485

(1)

Radioligand Binding

486

(1)

Endocannabinoids in Reproductive Tract Fluids and Organs

486

(6)

Pregnancy

492

(2)

Postnatal Development

494

(1)

Conclusions

495

(2)

Acknowledgments

497

(1)

References

497

(18)

Part VII Endocannabinoid Phylogenetics

515

(20)

Chapter 23 Distribution of Endocannabinoids and Their Receptors and Enzymes on the Tree of Life

517

(18)

John M. McPartland

Overview

518

(1)

Introduction

518

(1)

Mammals

519

(2)

Endocannabinoid Ligands

519

(1)

Endocannabinoid Receptors

520

(1)

Endocannabinoid-Metabolizing Enzymes

520

(1)

Other Vertebrates

521

(1)

Endocannabinoid Ligands

521

(1)

Endocannabinoid Receptors

521

(1)

Endocannabinoid-Metabolizing Enzymes

521

(1)

Invertebrates That Do Not Molt

521

(2)

Endocannabinoid Ligands

522

(1)

Endocannabinoid Receptors

522

(1)

Endocannabinoid-Metabolizing Enzymes

522

(1)

Invertebrates That Molt (Ecdysozoa)

523

(1)

Endocannabinoid Ligands

523

(1)

Endocannabinoid Receptors

523

(1)

Endocannabinoid-Metabolizing Enzymes

524

(1)

Plants

524

(1)

Endocannabinoid Ligands

524

(1)

Endocannabinoid Receptors

524

(1)

Endocannabinoid-Metabolizing Enzymes

524

(1)

Other Organisms

525

(1)

Endocannabinoid Ligands

525

(1)

Endocannabinoid Receptors

525

(1)

Endocannabinoid-Metabolizing Enzymes

525

(1)

Entourage Ligands, Analogous Receptors, and Other Enzymes

526

(1)

Entourage Ligands

526

(1)

Analogous Receptors

526

(1)

Other Enzymes

527

(1)

Estimating the Age of CBRs

527

(1)

Estimating the Age of Endocannabinoid Ligands

528

(1)

Addressing Chicken-or-Egg Questions

528

(1)

Conclusions

529

(1)

Acknowledgments

529

(1)

References

529

(6)

Part VIII Perspective

535

(20)

Chapter 24 Endocannabinoid-Based Molecules as Potential Therapeutic Drugs

537

(18)

Alessia Ligresti and Vincenzo Di Marzo

Introduction

537

(1)

Endocannabinoid Biosynthesis and Its Pharmacological Inhibition

538

(2)

Endocannabinoid Inactivation and Its Pharmacological Inhibition

540

(4)

Use of Endocannabinoid-Based Substances in Animal Models of Disorders

544

(4)

Multiple Sclerosis

544

(1)

Protection against Neuronal Hyperactivity

545

(1)

Pain

545

(1)

Anxiety and Aversive Memories (Posttraumatic Stress Disorders)

546

(1)

Diarrhea

546

(1)

Cancer

547

(1)

Other Possible Targets: Huntington's Chorea, Anorexia, Emesis, and Inflammatory and Autoimmune Disorders

548

(1)

Future Developments and Challenges

548

(1)

References

549

(6)

Index

555

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Endocannabinoids: The Brain and Body's Marijuana and Beyond

Summary

Table of Contents

Supplemental Materials