“Although many people drink alcohol regularly, only some become addicted. Several studies have shown that genetic and environmental factors contribute to individual differences in the vulnerability to the effects of alcohol. Among the environmental factors, stress is perhaps the most important trigger for relapse after a period of abstinence. Here we show that ethanol withdrawal symptoms were completely absent in cannabinoid CB1 receptor-deficient mice, although acute effects of ethanol and ethanol tolerance and preference were basically normal. Furthermore, foot-shock stress had no affect on alcohol preference in Cnr1−/− mice, although it induced a dramatic increase in Cnr1+/+ animals. These results reveal a critical role for the CB1 receptor in clinically important aspects of alcohol dependence and provide a rationale for the use of CB1 receptor antagonists in the treatment of alcohol addiction.”
“In summary, the endocannabinoid system does not seem to be crucial for the rewarding effects of ethanol and the manifestation of normal ethanol drinking behaviors. However, it appears to play an important role in the manifestation of stress-induced alcohol drinking and ethanol withdrawal. These results support the notion that the neuronal mechanisms involved in drug reinforcement are dissociable from those involved in withdrawal and reinstatement. Indeed, our results demonstrate that ethanol tolerance and physical dependence can be separated. Thus, CB1 receptor antagonists may be useful for the treatment of alcohol addiction.”