[Frontiers in Bioscience 14, 944-957, January 1, 2009]

Cannabinoid Receptors: A brief history and "what's hot".

Euan Scott Graham1, John Clive Ashton2, Michelle Glass1

1Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, 2Department of Pharmacology, University of Otago, New Zealand


1. Abstract
2. Introduction
3. The cannabinoids: A brief history
3.1. Cannabinoids and the discovery of cannabinoid receptors
3.2. Endocannabinoids 3.2.1 . Anandamide 3.2.2 . 2-arachidonoyl glycerol
3.3. Synthesis and degradation of endocannabinoids
3.4. Cannabinoid receptor mediated signalling
3.5. Cannabis based drugs
4. Exciting new developments in the cannabinoid field
4.1. CB1: a new target in the treatment of obesity
4.2. CB1: neurodegeneration and pain analgesia
4.3. CB1 receptor oligomerisation
4.4. CB2 expression in the brain: a new anti-inflammatory target
4.5. CB2 and multiple sclerosis
4.6. CB2 and neuroprotection following ischemia
4.7. CB2 in the spinal cord: regulation of neuropathic pain
4.8. Cannabinoids and arthritis
4.9. The development of new selective ligands
5. Summary and future perspective
6. Acknowledgements
7. References


Our understanding of the complexity of the endocannabinoid system has evolved considerably since the cloning of the receptors in the early 1990s. Since then several endogenous ligands have been identified and their respective biosynthetic pathways unravelled. This research has revealed the involvement of the cannabinoid system in a number of important physiological processes including the regulation of neurotransmitter release, pain and analgesia, energy homeostasis, and control of immune cell function. All of these events are mediated by two similar receptors, CB1 and CB2, which were initially thought to possess mutually exclusive expression profiles. Recent advances have begun to dissolve such absolutes with the discovery of CB2 in brain tissue and identification of a range of functions for CB1 in peripheral tissues. With improved understanding of the cannabinoid system comes the illumination of various roles in disease pathologies and identification of potential therapeutic targets. This review provides an overview of the current understanding of the endocannabinoid system, and then focuses on recent discoveries that we believe are likely to shape the future directions of the field.