The Endocannabinoid System and its Manifold Central Actions

  • M. Maccarrone
Reference work entry


Endocannabinoids are amides, esters, and ethers of long-chain polyunsaturated fatty acids, which act as endogenous agonists of cannabinoid receptors. Thus, they are able to mimic several pharmacological effects of Δ9-tetrahydrocannabinol, the psychoactive principle of Cannabis sativa preparations like hashish and marijuana. Anandamide (N-arachidonoylethanolamine) and 2-arachidonoylglycerol are the best-studied members of this new class of lipid mediators. It is now widely accepted that the biological activity of endocannabinoids is largely dependent on a “metabolic control,” which modulates the effects of these substances by modulating their in vivo concentration. Therefore, the metabolic routes that allow synthesis, transport, and degradation of endocannabinoids, and that altogether form the so-called “endocannabinoid system,” are the focus of intense research. This new system will be reviewed in the chapter, along with the molecular targets of endocannabinoids, and the signal transduction pathways triggered thereof. The aim of this update is also to put in a better perspective the cross-talks of endocannabinoids with other signaling molecules, and their implications for the manifold biological activities of these lipids within the central nervous system.


Lipid Raft Fatty Acid Amide Hydrolase Vanilloid Receptor Fatty Acid Amide Hydrolase Inhibitor Fatty Acid Amide Hydrolase Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

List of Abbreviations:


adenylyl cyclase


anandamide (N-arachidonoylethanolamine)




AEA membrane transporter


apoptosis signal-regulating kinase 1


bovine brain microvessels


type 1/2 cannabinoid receptor


central nervous system


calf pulmonary artery endothelium


cAMP response element




diacylglycerol lipase


depolarization-induced suppression of excitation


depolarization-induced suppression of inhibition


estrogen (17β-estradiol)


estrogen receptor


extracellular signal-regulated kinase


fatty acid amide hydrolase


focal adhesion kinase


γ-aminobutyric acid


G protein-coupled receptor




human umbilical vein endothelial cells


c-Jun N-terminal kinase


long term depression


long term potentiation


methyl-arachidonoyl fluorophosphonate


monoacylglycerol lipase


mitogen-activated protein kinase




group I metabotropic glutamate receptor


N-acylethanolamine-hydrolyzing acid amidase












nerve growth factor




nitric oxide


nitric oxide synthase








phosphatidylinositol 3-kinase


protein kinase A/B


phospholipase A1C, D




paraventricular nucleus


quantitative structure-activity-relationship


rat brain endothelium




signal transducer and activator of transcription


transient receptor potential channel vanilloid receptor subunit 1



I wish to thank Prof. A. Finazzi-Agrò (Department of Experimental Medicine and Biochemical Sciences, University of Rome “Tor Vergata”) for continuing interest and support, and all colleagues who gave their valuable contribution over the years to the studies on the endocannabinoid system in the CNS. I also thank Dr. A. Paradisi for the excellent production of the artwork. This investigation was supported by Ministero dell’Istruzione, dell’Università e della Ricerca (COFIN 2002 and 2003), and by Fondazione TERCAS (Research Programs 2004 and 2005).


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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • M. Maccarrone

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