Two of the major hallmarks of alcohol dependence are the establishment of tolerance to the acute effects of ethanol and the susceptibility to a withdrawal syndrome in the absence of the drug. Reports from various labs have indicated that the EC system is associated with both of these traits of dependence. In fact, most of the early work suggesting an interaction between ethanol and cannabinoid drugs (see historical perspectives section of this review) supports the view that the EC system is involved in mediating these two traits of addiction, but at the time these studies were conducted, the existence of the EC system and the molecular mechanisms by which ethanol and cannabinoids produce their effects was unknown. More recent work has demonstrated the symmetrical cross-tolerance that develops to the ataxic effects of cannabinoids and ethanol is CB1-dependent (da Silva et al., 2001; Lemos et al., 2007). In addition, studies in our lab have found that the cross-tolerance between ethanol and cannabinoids is a wide-spread phenomenon in the brain, and that this effect is correlated with alterations in CB1 expression (Pava et al., 2012).
