Endocannabinoid structure-activity relationships for interaction at the cannabinoid receptors

Prostaglandins Leukot Essent Fatty Acids. 2002 Feb-Mar;66(2-3):143-60. doi: 10.1054/plef.2001.0343.


Anandamide (N -arachidonoylethanolamine) was the first ligand to be identified as an endogenous ligand of the G-protein coupled cannabinoid CB1 receptor. Subsequently, two other fatty acid ethanolamides, N -homo- gamma -linolenylethanolamine and N -7,10,13,16-docosatetraenylethanolamine were identified as endogenous cannabinoid ligands. A fatty acid ester, 2-arachidonoylglycerol (2-AG), and a fatty acid ether, 2-arachidonyl glyceryl ether also have been isolated and shown to be endogenous cannabinoid ligands. Recent studies have postulated the existence of carrier-mediated anandamide transport that is essential for termination of the biological effects of anandamide. A membrane bound amidohydrolase (fatty acid amide hydrolase, FAAH), located intracellularly, hydrolyzes and inactivates anandamide and other endogenous cannabinoids such as 2-AG. 2-AG has also been proposed to be an endogenous CB2 ligand. Structure-activity relationships (SARs) for endocannabinoid interaction with the CB receptors are currently emerging in the literature. This review considers cannabinoid receptor SAR developed to date for the endocannabinoids with emphasis upon the conformational implications for endocannabinoid recognition at the cannabinoid receptors.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Cannabinoid Receptor Modulators
  • Cannabinoids / chemistry
  • Cannabinoids / metabolism*
  • Cannabinoids / pharmacology*
  • Eicosanoids / chemistry
  • Eicosanoids / metabolism*
  • Eicosanoids / pharmacology*
  • Endocannabinoids
  • Models, Molecular
  • Molecular Structure
  • Receptors, Cannabinoid
  • Receptors, Drug / agonists
  • Receptors, Drug / chemistry
  • Receptors, Drug / metabolism*
  • Structure-Activity Relationship
  • Substrate Specificity


  • Cannabinoid Receptor Modulators
  • Cannabinoids
  • Eicosanoids
  • Endocannabinoids
  • Receptors, Cannabinoid
  • Receptors, Drug