International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB1 and CB2

Roger Guy Pertwee, A. C. Howlett, M. E. Abood, S. P. H. Alexander, V. Di Marzo, M. R. Elphick, P. J. Greasley, H. S. Hansen, G. Kunos, K. Mackie, R. Mechoulam, R. A. Ross

Research output: Contribution to journalLiterature reviewpeer-review

1184 Citations (Scopus)


There are at least two types of cannabinoid receptors (CB1 and CB2). Ligands activating these G protein-coupled receptors (GPCRs) include the phytocannabinoid Delta(9)-tetrahydrocannabinol, numerous synthetic compounds, and endogenous compounds known as endo-cannabinoids. Cannabinoid receptor antagonists have also been developed. Some of these ligands activate or block one type of cannabinoid receptor more potently than the other type. This review summarizes current data indicating the extent to which cannabinoid receptor ligands undergo orthosteric or allosteric interactions with non-CB1, non-CB2 established GPCRs, deorphanized receptors such as GPR55, ligand-gated ion channels, transient receptor potential (TRP) channels, and other ion channels or peroxisome proliferator-activated nuclear receptors. From these data, it is clear that some ligands that interact similarly with CB1 and/or CB2 receptors are likely to display significantly different pharmacological profiles. The review also lists some criteria that any novel "CB3" cannabinoid receptor or channel should fulfil and concludes that these criteria are not currently met by any non-CB1, non-CB2 pharmacological receptor or channel. However, it does identify certain pharmacological targets that should be investigated further as potential CB3 receptors or channels. These include TRP vanilloid 1, which possibly functions as an ionotropic cannabinoid receptor under physiological and/or pathological conditions, and some deorphanized GPCRs. Also discussed are 1) the ability of CB1 receptors to form heteromeric complexes with certain other GPCRs, 2) phylogenetic relationships that exist between CB1/CB2 receptors and other GPCRs, 3) evidence for the existence of several as-yet-uncharacterized non-CB1, non-CB2 cannabinoid receptors; and 4) current cannabinoid receptor nomenclature.

Original languageEnglish
Pages (from-to)588-631
Number of pages44
JournalPharmacological Reviews
Issue number4
Publication statusPublished - Dec 2010


  • protein-coupled-receptor
  • free fatty-acids
  • anandamide-induced vasorelaxation
  • proliferator-activated receptors
  • vanilloid type-1 receptors
  • CA2+-activated K+ channels
  • trigeminal sensory neurons
  • dependent vascular actions
  • potential cation channels
  • N-arachidonoyl-dopamine


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