In the earliest report indicating a potential therapeutic potential of cannabinoid drugs for the treatment of AUDs, the authors describe the use of a synthetic analog of THC, pyrahexyl, given to ameliorate withdrawal symptoms (Thompson and Proctor, 1953). Although far from a rigorous, controlled clinical trial, this study provides anecdotal evidence indicating that acute withdrawal symptoms including irritability, loss of appetite, and insomnia are at least temporarily ameliorated by administration of this compound. Preclinical studies, however, dispute the beneficial effects of cannabinoid administration on ethanol withdrawal symptoms. Acute administration of THC to mice given three days of continuous ethanol vapor treatment produced higher handling-induced convulsion (HIC) scores and a longer duration withdrawal than subjects given vehicle upon removal from the chambers (Kralik et al., 1976; Sprague and Craigmill, 1978). One potential caveat to these studies is that acute administration of CB1 agonists can generate hyper-reflexive responses that manifest as eccentric jumping when the animal is slightly perturbed (Dewey, 1986; Patel and Hillard, 2001). It is possible that early studies examining the effect of acutely administered cannabinoids on HIC scores during
