Figure 2 shows the results of tests with THC, anandamide, and FAAH and MAGL inhibitors (PF3845 and JZL184, respectively) in mice trained to discriminate 5.6 mg/kg THC from vehicle. THC was tested twice, once at the beginning of the study and again at the end of the study. In both instances, mice dose-dependently selected the THC lever, with ED50 values of 2.22 mg/kg (95% CI: 1.39 – 3.55 mg/kg) and 1.72 mg/kg (95% CI: 1.08 – 2.74 mg/kg) at the start (Fig. 2, panel A) and the end (Fig. 2, panel B) of the study, respectively. In contrast, PF3845 did not substitute for THC when evaluated alone (Fig. 2, panel A). However, when 10 mg/kg PF3845 was tested in combination with anandamide, a dose-dependent increase in responding on the THC-associated aperture occurred, with a maximum 64% responding on the drug-associated side at a dose combination of 10 mg/kg PF3845 and 10 mg/kg anandamide. Although full substitution did not occur, inspection of data for individual subjects revealed that 4 of 7 mice tested with this dose combination distributed greater than 90%
