A retrospective examination of the early literature on the interactions between ethanol and cannabinoids finds clear evidence for the involvement of the EC system in the acute reinforcing properties of ethanol and the neuroadaptive changes that occur with its chronic abuse. However, it was not until the 1990’s that the molecular constituents of the EC system were discovered, and only in the past decade has the interaction between ethanol and the EC system been directly investigated. From these studies it is apparent that EC release in response to ethanol mediates the reinforcing properties of this drug and that chronic ethanol use resulting in tolerance and dependence dramatically alters the function of EC signaling. However, our understanding of the mechanisms responsible for the changes in EC signaling in response to chronic ethanol is lacking, and the role of EC system in regulating specific circuits associated with addiction processes is limited. Future work with more standardized methodologies will be needed to better grasp the complexity underlying the interaction between this neuromodulatory system and alcohol dependence. In addition, novel areas of research continue to emerge with basic discoveries surrounding the molecular constituents of the EC system.
