The endocannabinoid system: current pharmacological research and therapeutic possibilities

In the relatively short period of time since the discovery of cannabinoid receptors and their endogenous ligands, the endocannabinoids, an intensive research effort has resulted in the identification of agents that affect all aspects of the endocannabinoid system. The cannabinoid(1) receptor antagonist rimonabant is in phase III clinical trials for the treatment of obesity and as an aid to smoking cessation, and cannabinoid(2) receptor agonists are promising in animal models of inflammatory and neuropathic pain. In the present MiniReview, the endocannabinoid system is described from a pharmacological perspective. The main topics covered are: the mechanism of action of cannabinoid(2) receptor agonists; identification of the endocannabinoid(s) involved in retrograde signalling; the elusive mechanism(s) of endocannabinoid uptake; therapeutic possibilities for fatty acid amide hydrolase inhibitors; and the cyclooxygenase-2 and lipoxygenase-derived biologically active metabolites of the endocannabinoids.