986 Fig. 3 Regions of interest; based on pooled group activation maps of THC and placebo; a reward anticipation; b reward feedback. L=left, R=right Psychopharmacology (2012) 219:981–990 change for a miss but not for a hit in the posterior cingulate (F = 6.3, p < 0.05) and the middle orbitofrontal Fig. 4 Brain activity during anticipation. a Brain activity during anticipation averaged across ROIs; b right inferior orbitofrontal cortex. Error bars denote standard error of the mean (SEM). a.u.= arbitrary units; R=right; Inf=inferior. p values are not corrected for multiple comparisons cortex (F = 12.6, p < 0.01), while THC reduced the signal change related to a hit but not a miss in the right superior frontal cortex (F = 6.7, p < 0.05). A trend for an interaction effect of drug by condition in the left inferior temporal gyrus indicated a larger attenuation of brain activity during hits than misses after THC administration (F = 3.5; p < 0.1). However, none of these ROI effects survived correction for multiple comparisons (see Tables 3, 4, S1b and S2b). Discussion In this study, the role of the eCB system in reward processing in humans was examined by assessing the effects of THC administration on brain activity during monetary reward anticipation and feedback. Subjects showed similar behavioral responses to reward during THC and placebo, with faster responses if a reward could be won. THC administration attenuated brain activity during reward feedback compared to placebo. THC did not affect brain activity related to feedback if there was no possibility to win a reward. These results indicate that THC administration predominantly reduces the effect of feedback in situations where there is the possibility to earn a reward and suggest involvement of the eCB system in appreciation of a received reward. This effect was largest in the inferior