International Union of Pharmacology. XXVII. Classification of cannabinoid receptors

A C Howlett, F Barth, T I Bonner, G Cabral, P Casellas, W A Devane, C C Felder, M Herkenham, K Mackie, B R Martin, R Mechoulam, R G Pertwee

Research output: Contribution to journalLiterature review

2308 Citations (Scopus)


Two types of cannabinoid receptor have been discovered so far, CB1 (2.1:CBD:1:CB1:), cloned in 1990, and CB2 (2.1:CBD:2:CB2:), cloned in 1993. Distinction between these receptors is based on differences in their predicted amino acid sequence, signaling mechanisms, tissue distribution, and sensitivity to certain potent agonists and antagonists that show marked selectivity for one or the other receptor type. Cannabinoid receptors CB1 and CB2 exhibit 48% amino acid sequence identity. Both receptor types are coupled through G proteins to adenylyl cyclase and mitogen-activated protein kinase. CB1 receptors are also coupled through G proteins to several types of calcium and potassium channels. These receptors exist primarily on central and peripheral neurons, one of their functions being to inhibit neurotransmitter release. Indeed, endogenous CB1 agonists probably serve as retrograde synaptic messengers. CB2 receptors are present mainly on immune cells. Such cells also express CB1 receptors, albeit to a lesser extent, with both receptor types exerting a broad spectrum of immune effects that includes modulation of cytokine release. Of several endogenous agonists for cannabinoid receptors identified thus far, the most notable are arachidonoylethanolamide, 2-arachidonoylglycerol, and 2-arachidonylglyceryl ether. It is unclear whether these eicosanoid molecules are the only, or primary, endogenous agonists. Hence, we consider it premature to rename cannabinoid receptors after an endogenous agonist as is recommended by the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. Although pharmacological evidence for the existence of additional types of cannabinoid receptor is emerging, other kinds of supporting evidence are still lacking.

Original languageEnglish
Pages (from-to)161-202
Number of pages42
JournalPharmacological Reviews
Issue number2
Publication statusPublished - 2002


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