ABSTRACT
The discovery of endocannabinoids, endogenous ligands of cannabinoid receptors, opened a new age in research not only on the biology of marijuana but also on the natural role of fatty acid derivatives like the N-acylethanolamines and the monoacylglycerols. In fact, the endocannabinoids discovered so far all happen to be polyunsaturated homologues belonging to these two classes of lipids. Certainly the most studied endocannabinoids are anandamide (N-arachidonoylethanolamine) and 2-arachidonoylglycerol. Concomitantly to the discovery of the properties as cannabinoid receptor ligands of these two compounds, two other fatty acid derivatives, N-palmitoylethanolamine and oleamide (cis-9-octadecenoamide), were also found to exhibit cannabimimetic activity in some tests despite their very low affinity for the two cannabinoid receptor subtypes known to date. In this chapter, we review the landmarks in the history of endocannabinoids, starting with the background leading to their discovery and the analytical techniques developed for their analysis and quantification in tissues and biological fluids, and ending with a description of the mechanisms responsible for the regulation of their tissue levels, and of their possible physiological and pathological role. We also briefly describe the possible biological and evolutionary relevance of the finding of these lipids in simple animal organisms and plants, and discuss the possible implications of the presence of cannabimimetic fatty acid derivatives in foods.
