The enigmatic pharmacology of GPR55

Trends Pharmacol Sci. 2009 Mar;30(3):156-63. doi: 10.1016/ Epub 2009 Feb 21.


Preliminary data presented at conferences and in the patent literature introduced the possibility the orphan receptor GPR55 might account for some of the well-documented non-CB(1), non-CB(2) effects reported for certain cannabinoid ligands. Several peer-reviewed publications have recently emerged in which the pharmacology of the cannabinoids at GPR55 has been probed in more depth. Despite this, the classification of GPR55 as a cannabinoid receptor remains a contentious issue. The weight of evidence points to GPR55 as a receptor that is activated by certain cannabinoid ligands and by the bioactive lipid l-alpha-lysophosphatidylinsoitol. It couples to G(12) proteins, activates RhoA and mobilizes intracellular Ca(2+), possibly in an agonist- and tissue-dependant manner, thus displaying 'agonist functional selectivity'. Here, I review the recent literature in an effort to glean the key controversies and outstanding questions surrounding the interaction between cannabinoids and this orphan receptor.

Publication types

  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Cannabinoid Receptor Agonists
  • Cannabinoid Receptor Modulators / metabolism*
  • Cannabinoid Receptor Modulators / pharmacology
  • Cannabinoids / metabolism*
  • Cannabinoids / pharmacology
  • Ligands
  • Lysophospholipids / metabolism
  • Lysophospholipids / pharmacology
  • Mice
  • Receptors, Cannabinoid / classification
  • Receptors, Cannabinoid / physiology*
  • Receptors, Lysophospholipid / agonists
  • Receptors, Lysophospholipid / classification
  • Receptors, Lysophospholipid / physiology*
  • Signal Transduction / drug effects
  • Structure-Activity Relationship


  • Cannabinoid Receptor Agonists
  • Cannabinoid Receptor Modulators
  • Cannabinoids
  • GPR55 protein, mouse
  • Ligands
  • Lysophospholipids
  • Receptors, Cannabinoid
  • Receptors, Lysophospholipid
  • lysophosphatidylinositol