Assessment of forebrain-dependent trace eyeblink conditioning in chronic cannabis users.

While CB1 knockout mice exhibit striking impairments on a cerebellar-dependent task called delay eyeblink conditioning (dEBC), these animals demonstrate intact forebrain-dependent trace EBC (tEBC). Although heavy human cannabis users also show impaired delay EBC, their performance on tEBC is currently unknown. Therefore, 13 heavy cannabis users and 13 cannabis naive controls completed a tEBC procedure. The cannabis group exhibited similar rates of conditioned responding compared to controls in the acquisition and extinction phase. Consistent with reports of overt attentional abnormalities, the cannabis group exhibited decreased N100 ERP amplitudes to the tone CS that were unrelated to mean levels of conditioning across blocks during the acquisition phase. The lack of a significant effect of heavy cannabis use on tEBC reported here, combined with the previous report of impaired dEBC in such users, mirrors the findings observed in CB1 knockout mice, and suggests that the cannabinoid system differentially mediates forebrain- and cerebellar-dependent learning processes in both humans and animals.