In December 1992 Devane and his collaborators (Devane et al., 1992) reported
the isolation and structure elucidation of a porcine brain lipid component that selectively
displaced the binding of a high-affinity cannabinoid receptor ligand to
brain membrane preparations. This compound was the ethanolamide of arachidonic
acid (20:4, n-6) and was named anandamide (AEA) (Figure 1), after the
Sanskrit word for “bliss”, ananda. AEA was shown to be active in the tetrade of
mouse behavioral tests suggestive of cannabinoid-like activity, i.e. inhibition of
locomotor and rearing activity, hypothermy, catalepsy, and analgesia (Fride and
Mechoulam, 1993; Crawley et al., 1993). Another derivative of arachidonic acid
that activates cannabinoid receptors, 2-arachidonoylglycerol (2-AG), was discovered
in 1995 (Mechoulam et al., 1995; Sugiura et al., 1995). Although structurally
different from plant-derived cannabinoids, these compounds, in analogy with the
“endorphins” (i.e. the endogenous ligands of opiate receptors), were named “endocannabinoids”
