increased anandamide levels observed in non-handled isolates. Our data are consistent with the observation that handling decreased the anxiolytic effect of the FAAH inhibitor URB597 (Haller et al., 2009). Handling and URB597 may rely on similar endocannabinoid system-dependent mechanisms. Chronic handling may also facilitate habituation to stressors in an endocannabinoid-dependent manner, as handling itself eventually loses aversive quality after chronic exposure. Our data support the use of chronic handling, as a research tool, to manipulate the endocannabinoid system.