Mechoulam Cannabinoids as Therapeutics

1. Auflage 2006
ISBN: 978-3-7643-7358-0
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 268 Seiten

Reihe: Milestones in Drug Therapy

Only a few years ago the endocannabinoid system was unknown. Today we are aware that endocannabinoids are involved in many of the functions of the mammalian body - in neuroprotection, appetite and suckling, pain, reproduction, anxiety, memory, bone formation etc. This volume presents an up-to-date picture of some of the major fields of endocannabinoid research. It summarizes the actions of the endocannabinoids on various physiological systems and opens new therapeutic windows to a large number of diseases.
The first chapter, on the use of Cannabis in India, can be viewed as an expression of thanks to the herbal practitioners, who for centuries passed on the medical traditions associated with the drug. The chapter on chemistry is a short summary of active plant, synthetic and endogenous cannabinoids being investigated today, many of which are mentioned later in the book. Cannabidiol is an unusual cannabinoid - it does not bind to the known receptors and yet exerts a variety of effects. Hence a chapter is devoted to it. Further chapters deal with the endocannabinoid system and the endocannabinoids in a variety of conditions and physiological systems. The concluding chapter describes the research done on Sativex®, a standardized plant extract, shortly to be introduced in Canada as a drug for multiple sclerosis.
The intended audience is drug researchers (medicinal chemists, pharmacologists, clinicians), neuroscientists, physiologists, and clinicians interested in the effect of the endocannabinoid system in various physiological systems.

Autoren/Hrsg.

Mechoulam, Raphael

Inhaltsverzeichnis

1;Contents;6
2;List of contributors;8
3;Preface;10
4;Cannabis in India: ancient lore and modern medicine;12
4.1;Introduction: Ayurvedic medicine;12
4.2;Cannabis: its history in the medicine of India;13
4.3;A nexus with Western medicine;17
4.4;Politics and cannabis collide;20
4.5;Cannabis in contemporary Ayurvedic medicine;22
4.6;The scientific basis of Indian cannabis claims;23
4.7;Cannabis in India in context;27
4.8;References;28
5;Cannabinoid chemistry: an overview;34
5.1;Introduction;34
5.2;Natural cannabinoids;34
5.3;Endogenous cannabinoids;36
5.4;Synthetic cannabinoid receptors agonists/antagonists;38
5.5;1;47
5.6;2,;47
5.7;3;48
5.8;4;48
5.9;5;48
5.10;6;49
5.11;7;49
5.12;8;49
5.13;9;49
5.14;8;50
5.15;9;50
5.16;10;50
5.17;11);50
5.18;12);50
5.19;Conclusions;51
5.20;References;52
6;Cannabidiol as a potential medicine;58
6.1;Introduction;58
6.2;Epilepsy;59
6.3;Other central motor disorders;63
6.4;Anxiety;63
6.5;Psychotic illnesses;64
6.6;Neurotoxicity;65
6.7;Inflammation;66
6.8;Other potential therapeutic targets;68
6.9;Concluding discussion;70
6.10;References;71
7;Endocannabinoids and regulation of fertility;77
7.1;Introduction;77
7.2;Endocannabinoid degradation during pregnancy;78
7.3;FAAH and human reproduction;82
7.4;FAAH and the regulation of spermatogenesis;84
7.5;Conclusions and perspectives;85
7.6;References;86
8;Cannabinoids in neurodegeneration and neuroprotection;89
8.1;Introduction;89
8.2;Mechanisms involved in neuroprotection by cannabinoids;91
8.3;Cannabinoids in acute neurodegeneration;98
8.4;Cannabinoids in chronic neurodegeneration;100
8.5;Concluding remarks and future perspectives;110
8.6;References;111
9;Role of the endocannabinoid system in learning and memory;120
9.1;Introduction;120
9.2;Behavioral effects of cannabinoid agonists in learning paradigms;120
9.3;Endocannabinoid modulation of cognitive processes;128
9.4;Neuroanatomical locus of effects;133
9.5;Cellular effects/interactions with other transmitter systems;135
9.6;Role of endocannabinoids in synaptic plasticity;137
9.7;Conclusions on the effects of endocannabinoids on cognition;140
9.8;References;141
10;Cannabinoids and anxiety;150
10.1;Introduction;150
10.2;Anxiolytic effects of CB1 receptor antagonists;150
10.3;Cannabinoid receptor agonists;151
10.4;CB1 receptor- knockout studies;152
10.5;Anandamide hydrolysis and anxiety;152
10.6;Discussion of animal studies;152
10.7;Human studies;153
10.8;Discussion;155
10.9;References;155
11;Cannabinoid targets for pain therapeutics;157
11.1;Introduction;157
11.2;Effects of direct-acting cannabinoid receptor agonists;158
11.3;Brain action of cannabinoid agonists;158
11.4;Spinal action of cannabinoid agonists;159
11.5;Peripheral action of cannabinoid agonists;159
11.6;Effects of cannabinoid CB2- specific agonists;160
11.7;Effects of cannabinoid agonists in humans;160
11.8;Development of non-psychotropic cannabinoids;163
11.9;Development of inhibitors of FAAH;164
11.10;Development of inhibitors of cellular transport of endogenous cannabinoids;165
11.11;Synergism between cannabinoid and opioid agonists;165
11.12;Summary and conclusions;166
11.13;References;166
12;Potential use of cannabimimetics in the treatment of cancer;173
12.1;Introduction;173
12.2;Cannabinoid receptor stimulation causes inhibition of cancer growth through multiple intracellular mechanisms and pathways;175
12.3;Cannabinoid receptor stimulation leads to inhibition of tumor angiogenesis and metastasis;178
12.4;The endocannabinoid system attempts to provide protection from the growth and spread of cancer;179
12.5;Non- CB1/-CB2 receptors are also involved in ( endo) cannabinoid anti- tumor actions;180
12.6;Substances targeting the endocannabinoid system in cancer therapy – pros and cons;182
12.7;References;184
13;Cannabinoids: effects on vomiting and nausea in animal models;190
13.1;Introduction;190
13.2;Cannabinoids as anti-emetics;191
13.3;Anti-emetic effects of cannabinoids in human clinical trials;192
13.4;Effects of cannabinoids on emesis in animals;193
13.5;Conditioned gaping in shrews: a model for ANV;198
13.6;Conditioned gaping in rats: a model of nausea;199
13.7;Conclusions;202
13.8;References;203
14;The skeleton: stone bones and stoned heads?;208
14.1;Introduction;208
14.2;Strategy;209
14.3;Expression of cannabinoid receptors in bone;209
14.4;Cannabinoid ligands regulate bone cell differentiation and activity;210
14.5;Cannabinoid receptor signalling regulates bone mass;210
14.6;Summary;210
14.7;References;211
15;Cannabinoids and drugs of abuse;214
15.1;Introduction;214
15.2;Tolerance;215
15.3;Physical dependence;216
15.4;Behavioral sensitization;216
15.5;Drug discrimination;217
15.6;Self-administration;218
15.7;Conditioned place preference;219
15.8;Neurochemical correlates of cannabinoid rewarding properties;219
15.9;Cannabinoid system and drug addiction;220
15.10;References;222
16;Cannabinoids in appetite and obesity;226
16.1;Introduction;226
16.2;Cannabinoid agonists and appetite;226
16.3;Cannabinoid antagonists and obesity;228
16.4;1);230
16.5;Mechanism of action of cannabinoid ligands on food intake and energy balance;231
16.6;Conclusion;233
16.7;References;234
17;The development of Sativex – a natural cannabis-based medicine;238
17.1;History of the development;238
17.2;The endogenous cannabinoid system;240
17.3;Cannabinoid receptor ligands;241
17.4;Classification of cannabinoids;241
17.5;Production of cannabis-based medicines;242
17.6;Rationale for the development of a cannabis-based medicine as a whole- plant extract;242
17.7;Regulatory requirements;243
17.8;Breeding of cannabis plants for generation of cannabis extracts;244
17.9;Cultivation of chemovars for generation of cannabis extracts;246
17.10;BDS content;248
17.11;Characterization, control and specification of BDS;250
17.12;Finished product – BDP: formulation and filling;251
17.13;Administration of Sativex;251
17.14;achieving the therapeutic window;251
17.15;Clinical effects of Sativex;252
17.16;Clinical programme results;254
17.17;Phase II data;254
17.18;Phase III data;254
17.19;Neuropathic pain in MS;256
17.20;Neuropathic pain in brachial plexus avulsion;258
17.21;Symptoms of MS;259
17.22;Effect on sleep;260
17.23;What do patients want?;261
17.24;Long-term data;262
17.25;Safety;262
17.26;Intoxication;263
17.27;Dosing;265
17.28;Conclusion;266
17.29;References;267
18;Index;271