As mentioned at the beginning of this review, the rate of co-abuse of ethanol and cannabis is strikingly high, but surprisingly few studies have been conducted to examine the effect of co-abuse on the EC system or behaviors associated with ethanol/cannabis consumption. A few studies in rodents have reported that administration of CB1 agonists facilitates ethanol consumption (Gallate et al., 1999; Linsenbardt and Boehm, 2009; Vinod et al., 2008b), and a series of reports have implicated the activation of CB1 by exogenous cannabinoids as a factor in enhancing reinstatement to ethanol seeking (Alén et al., 2009; López-Moreno et al., 2004). In addition, one study found that administration of THC to ethanol-consuming rats produced a synergistic effect to impair memory processes (Ciccocioppo et al., 2002). Beyond the effect of these drugs on the reward circuitry of the brain, several reports suggest that co-administration of ethanol and CB1 agonists may facilitate the neurotoxic effects of ethanol on neural tissue (Alén et al., 2010; Hansen et al., 2008). Interestingly, mice with a null mutation of DAGLα have reduced neurogenesis in the hippocampus (Gao
