Cannabimimetic fatty acid derivatives: the anandamide family and other endocannabinoids

Curr Med Chem. 1999 Aug;6(8):721-44.


In agreement with the highly lipophilic nature of (-)-delta9-tetrahydrocannabinol, all the endogenous ligands of cannabinoid receptors identified so far are derivatives of long chain fatty acids. N- Arachidonoylethanolamine (anandamide) and some of its polyunsaturated congeners have been found in mammalian brain and shown to activate the CB1 and, with a lower efficacy, CB2 cannabinoid receptor subtypes. More recently, 2-arachidonoylglycerol (2-AG), a widespread intermediate in the metabolism of phosphoglycerides, diacylglycerols and triglycerides, was also found to activate the cannabinoid receptors. The capability of palmitoylethanolamide, an anti-inflammatory metabolite, to activate CB2-like receptors is still being debated. Here we review: 1) the metabolic pathways suggested so far to underlie the biosynthesis and inactivation of anandamide and 2-AG, and 2) the current knowledge of the chemical bases for the interactions of anandamide and 2-AG with proteins of the endogenous cannabinoid system characterized so far, i.e. the CB1 and CB2 receptor subtypes, the membrane anandamide carrier , which facilitates anandamide diffusion into cells, and the enzyme fatty acid amide hydrolase , which catalyzes anandamide and, to a certain extent, 2-AG hydrolysis in vivo.

Publication types

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

MeSH terms

  • Animals
  • Arachidonic Acids / chemistry
  • Arachidonic Acids / pharmacology*
  • Cannabinoid Receptor Modulators
  • Cannabinoids / chemical synthesis
  • Cannabinoids / pharmacology*
  • Dronabinol / analogs & derivatives
  • Dronabinol / chemistry
  • Dronabinol / pharmacology
  • Endocannabinoids
  • Fatty Acids / chemical synthesis
  • Fatty Acids / pharmacology*
  • Hallucinogens / chemistry
  • Hallucinogens / pharmacology
  • Humans
  • Polyunsaturated Alkamides


  • Arachidonic Acids
  • Cannabinoid Receptor Modulators
  • Cannabinoids
  • Endocannabinoids
  • Fatty Acids
  • Hallucinogens
  • Polyunsaturated Alkamides
  • Dronabinol
  • anandamide