A large body of evidence now exists to substantiate that the endocannabinoid, anandamide, activates TRPV1 receptors. It is a low intrinsic efficacy TRPV1 agonist that behaves as a partial agonist in tissues with a low receptor reserve, while in tissues with high receptor reserve and in circumstances associated with certain disease states, it behaves as a full agonist. The efficacy of anandamide as a TRPV1 agonist is influenced by a succession of factors including receptor reserve, phosphorylation, metabolism and uptake, CB₁ receptor activation, voltage, temperature, pH and bovine serum albumin. There are indications that the endocannabinoid system may play a role in the modulation of TRPV1 receptor activation. The activation of TRPV1 receptors by anandamide has potential implications in the treatment of inflammatory, respiratory and cardiovascular disorders. The relative importance of anandamide as a physiological and/or pathophysiological TRPV1 receptor agonist in comparison to other potential candidates has yet to be revealed.

British Journal of Pharmacology (2003) 140, 790–801. doi:10.1038/sj.bjp.0705467