CNR1 and alcohol abuse: Given that CBD acts as a natural antagonist of CB1R, and CB1R antagonists have been shown to reduce the self-administration and appetitive value of ethanol in rodent models (Arnone et al., 1997; Economidou et al., 2006), as well as inhibit the development of rapid tolerance to ethanol in rats (Lemos et al., 2007), CBD had long been viewed as a promising pharmacotherapy candidate to treat alcohol used disorders (AUD).