Journal of Neuroimmune Pharmacology

, Volume 5, Issue 1, pp 103–121

Non-CB1, Non-CB2 Receptors for Endocannabinoids, Plant Cannabinoids, and Synthetic Cannabimimetics: Focus on G-protein-coupled Receptors and Transient Receptor Potential Channels

Invited Review

DOI: 10.1007/s11481-009-9177-z

Cite this article as:
De Petrocellis, L. & Di Marzo, V. J Neuroimmune Pharmacol (2010) 5: 103. doi:10.1007/s11481-009-9177-z


The molecular mechanism of action of Δ9-tetrahydrocannabinol (THC), the psychotropic constituent of Cannabis, has been a puzzle during the three decades separating its characterization, in 1964, and the cloning, in the 1990s, of cannabinoid CB1 and CB2 receptors. However, while these latter proteins do mediate most of the pharmacological actions of THC, they do not seem to act as receptors for other plant cannabinoids (phytocannabinoids), nor are they the unique targets of the endogenous lipids that were originally identified in animals as agonists of CB1 and CB2 receptors, and named endocannabinoids. Over the last decade, several potential alternative receptors for phytocannabinoids, endocannabinoids, and even synthetic cannabimimetics, have been proposed, often based uniquely on pharmacological evidence obtained in vitro. In particular, the endocannabinoid anandamide, and the other most abundant Cannabis constituent, cannabidiol, seem to be the most “promiscuous” of these compounds. In this article, we review the latest data on the non-CB1, non-CB2 receptors suggested so far for endocannabinoids and plant or synthetic cannabinoids, and lay special emphasis on uncharacterized or orphan G-protein-coupled receptors as well as on transient receptor potential channels.


cannabinoid receptor TRP channel G-protein endocannabinoid phytocannabinoid GPR55 GPR119 

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Endocannabinoid Research Group, Institute of CyberneticsConsiglio Nazionale delle RicerchePozzuoliItaly
  2. 2.Endocannabinoid Research Group, Institute of Biomolecular ChemistryConsiglio Nazionale delle RicerchePozzuoliItaly

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