When its metabolism was not inhibited, anandamide failed to substitute for THC in mice (Vann et al., 2009; Wiley et al., 2011), as is consistent with most THC discrimination studies in rats (Burkey and Nation, 1997; Järbe et al., 2001; Wiley et al., 1998). The two FAAH inhibitors, PF3845 (Ahn et al., 2009) and URB597, produced different effects on anandamide substitution. Whereas PF3845 enhanced substitution of anandamide, URB597 did not. Neither compound produced THC-like effects on its own. The results with PF3845 are consistent with those of previous studies, in which inhibition of anandamide metabolism with URB597 (Solinas et al., 2007) or with phenylmethyl sulfonyl fluoride (PMSF) (Vann et al., 2009) also enhanced anandamide substitution. Cross-substitution of THC for anandamide has also been demonstrated in FAAH(−/−) mice trained to discriminate anandamide from vehicle (Walentiny et al., 2011). Together, these results suggest an overlap in the discriminative stimulus effects of anandamide and THC when the rapid metabolism of anandamide is inhibited, although the present URB597 results are at odds with this interpretation (however, see next paragraph). Interestingly, PF3845 did not shift
