Endocannabinoids and Their Pharmacological Actions

  • Roger G. PertweeEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 231)


The endocannabinoid system consists of G protein-coupled cannabinoid CB1 and CB2 receptors, of endogenous compounds known as endocannabinoids that can target these receptors, of enzymes that catalyse endocannabinoid biosynthesis and metabolism, and of processes responsible for the cellular uptake of some endocannabinoids. This review presents in vitro evidence that most or all of the following 13 compounds are probably orthosteric endocannabinoids since they have all been detected in mammalian tissues in one or more investigation, and all been found to bind to cannabinoid receptors, probably to an orthosteric site: anandamide, 2-arachidonoylglycerol, noladin ether, dihomo-γ-linolenoylethanolamide, virodhamine, oleamide, docosahexaenoylethanolamide, eicosapentaenoylethanolamide, sphingosine, docosatetraenoylethanolamide, N-arachidonoyldopamine, N-oleoyldopamine and haemopressin. In addition, this review describes in vitro findings that suggest that the first eight of these compounds can activate CB1 and sometimes also CB2 receptors and that another two of these compounds are CB1 receptor antagonists (sphingosine) or antagonists/inverse agonists (haemopressin). Evidence for the existence of at least three allosteric endocannabinoids is also presented. These endogenous compounds appear to target allosteric sites on cannabinoid receptors in vitro, either as negative allosteric modulators of the CB1 receptor (pepcan-12 and pregnenolone) or as positive allosteric modulators of this receptor (lipoxin A4) or of the CB2 receptor (pepcan-12). Also discussed are current in vitro data that indicate the extent to which some established or putative orthosteric endocannabinoids seem to target non-cannabinoid receptors and ion channels, particularly at concentrations at which they have been found to interact with CB1 or CB2 receptors.


2-Arachidonoylglycerol Anandamide Cannabinoid receptors Dihomo-γ-linolenoylethanolamide Docosahexaenoylethanolamide Docosatetraenoylethanolamide Eicosapentaenoylethanolamide Endocannabinoid pharmacology Haemopressin Lipoxin A4 N-arachidonoyldopamine Noladin ether N-oleoyldopamine Oleamide Pepcan-12 Pregnenolone Sphingosine Virodhamine 





Cannabinoid receptor type 1


Cannabinoid receptor type 2


Chinese hamster ovary


Guanosine diphosphate


Guanosine triphosphate


Human embryonic kidney




Transient receptor potential


TRP channel of ankyrin type 1


TRP channel of melastatin type 8


TRP channel of vanilloid type 1


TRP channel of vanilloid type 4


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.School of Medical Sciences, Institute of Medical SciencesUniversity of AberdeenAberdeenScotland, UK

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