The endocannabino M s b y

sponding receptors, i.e., the opioid system, have been conserved during evolution.1,2 We are now extending this cells, alters antigen processing and modulates the expression of select macrophage-associated proteins.11,14concept to include cannabinoid-signaling molecules. In the mammalian brain, cannabinoid 1 receptor (CB1-R) was cloned and sequenced in 1990,3 and evidence for a second CB2-R was obtained in 1993.4 Several studies suggest that anandamide is the endogenous agonist of CB1-R.5–7 Anandamide mimics most of the pharmacolo-gical and behavioral actions associated with cannabi-noids, i.e., D9-tetrahydrocannabinol (THC).5 Furthermore, enzymes for the synthesis and degradation of this signaling molecule have been found in mammals.8 Studies on anandamide amidohydrolase (anandamide amidase, fatty acid hydralase (FAAH)), responsible for the hydrolysis of anandamide,8,9 have shown that the enzyme may catalyze the hydrolysis of another putative neuroactive amide, the sleep-inducing oleoyl-amide.5 CB1-R also has been found in immune cells,4 which also synthesize anandamide.10,11 Like THC, the active ingre-A CANNABINOID SYSTEM IN INVERTEBRATES In invertebrates, the first example of an effect by cannabinoids was reported by Acosta-Urquidi and Chase.15 They showed that in isolated buccal and parieto-visceral ganglia of Aplysia californica, THC causes a depression in nerve cell excitability that is consistent with its reported effects in mammals. In 1976, McClean and Zimmerman16 showed in Tetrahymena pyriformis GL that THC elicited a dose-dependent effect on form/ movement, cellular growth and division in log growth phase. This effect was accompanied by up-regulation of cAMP levels in synchronously dividing Tetrahymena.17 In the sea urchin Strongylocentrotus purpuratus canna-binoids (THC and cannabidiol (CBD)) reduce the fertiliz-ing capacity of sperm cells.18,19 Pretreatment of sperm with THC prevents, in a dose and time-dependent manner, the triggering of the acrosome reaction by solubilized egg jelly. The motility of THC-treated sper