following a 12-day forced consumption paradigm (Naassila et al., 2004). Importantly, Vinod et al (2008b) also observed that the reduction in withdrawal severity could be reconstituted in wt mice by treating them with SR. Taken in the context of earlier studies reporting increased withdrawal severity following administration of CB1 agonists (Kralik et al., 1976; Sprague and Craigmill, 1978), these results suggest a positive correlation between CB1 activation and HIC severity. However, these early studies used THC, a full CB1 agonist, to enhance withdrawal severity, and in addition to the potential confounds associated with using CB1 agonists to modulate HIC measures (see historical perspectives section), these studies reported differential findings based on the measure of withdrawal. To more fully delineate the relationship between CB1 activation and withdrawal severity studies implementing partial agonists are useful, but at present these data are nearly absent from the literature. One study using FAAH KO mice found that these mice displayed reduced severity of HICs following withdrawal from chronic ethanol (Vinod et al., 2008a). These data indicate that the EC system is involved in modulating ethanol withdrawal symptoms in a complex way, and future work should focus on the utility of partial CB1 agonists as well
