Endocannabinoid System: An Update


The endocannabinoid system (ECS) is nowadays considered as an important neurotransmitter system and, although the chemistry, biochemistry and pharmacology of endocannabinoids (eCBs) have been widely investigated, quite some pieces are still missing to fully understand how this system works. The discovery of anandamide (AEA) and 2‐arachidonoylglycerol (2‐AG) dates back to the beginning of 1990 and, since then, their molecular targets, biosynthetic and catabolic enzymes have been identified. In addition, selective pharmacological and genetic tools have been developed both to explore alternative metabolic routes and to produce eCB‐based drugs as therapeutics for the prevention/treatment of a variety of diseases.

In this article, we will review the metabolic pathways of eCBs, and the latest advances on their potential receptor targets.

Key Concepts

  • The endocannabinoid system is an endogenous network including endocannabinoids, a complex array of receptors, biosynthetic and hydrolytic enzymes, as well as membrane transporters.
  • Endocannabinoids are derivatives of the arachidonic acid.
  • The two most important endocannabinoid transmitters, anandamide and 2‐arachidonoylglycerol, are produced and eliminated through several enzyme pathways.
  • Endocannabinoids play their main roles by targeting both cannabinoid and other membrane and nuclear receptors.
  • The binding of endocannabinoids to cannabinoid, vanilloid and peroxisome proliferator‐activated receptors triggers several signal transduction pathways.
  • The endocannabinoid system is a pleiotropic signalling system that is widely distributed in the central and peripheral nervous systems.
  • Alterations of circulating endocannabinoids levels are involved in the dysregulation of activity of important physiological systems.
  • A deep knowledge of the endocannabinoid system signalling might be translated into the development of pathway‐selective drugs for therapeutic benefit.

Keywords: anandamide; 2‐arachidonoylglycerol; cannabinoid receptors; endocannabinoids; metabolic pathways

Figure 1. Chemical structures of AEA and 2‐AG.
Figure 2. The main metabolic pathways of AEA and 2‐AG. See text for abbreviations and details.
Figure 3. The endogenous network of AEA and 2‐AG metabolic enzymes and their main receptors. Enzymes and receptors are the coloured circles (green circle, biosynthetic enzymes; orange circle, hydrolytic enzymes; yellow circle, molecular targets) and mutual interactions among them are represented by lines (dotted line, biosynthetic enzymes; solid line, hydrolytic enzymes; red line, molecular targets). Turquoise circles represent the main degradation products.


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Battista, Natalia, Maccarrone, Mauro, and Bari, Monica(Sep 2017) Endocannabinoid System: An Update. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0027093]