‘Endocannabinoids’ and other fatty acid derivatives with cannabimimetic properties: biochemistry and possible physiopathological relevance

The only endogenous substances isolated and characterised so far that are capable of mimicking the pharmacological actions of the active principle of marijuana, (−)-Δ⁹-tetrahydrocannabinol, are amides and esters of fatty acids. Some of these compounds, like anandamide (N-arachidonoylethanolamine) and 2-arachidonoylglycerol, act as true ‘endogenous cannabinoids’ by binding and functionally activating one or both cannabinoid receptor subtypes present on nervous and peripheral cell membranes. The metabolic pathways and molecular mode of actions of these metabolites, as well as their possible implication in physiopathological responses, are reviewed here.