Behavioral pharmacology paradigms have been used for early efficacy testing of novel compounds for alcohol use disorder (AUD). However, the degree to which early efficacy in the human laboratory predicts clinical efficacy remains unclear. For behavioral pharmacology, we computed medication effects on alcohol-induced stimulation, sedation, and craving during the alcohol administration (k = 51 studies, 24 medications). For RCTs, we computed medication effects on any drinking and heavy drinking (k = 118 studies, 17 medications).

We used medication as the unit of analysis and applied the Williamson-York bivariate weighted least squares estimation to preserve the errors in both the independent and dependent variables. Results, with correction for publication bias, revealed a significant and positive relationship between medication effects on alcohol-induced stimulation (β = 1.18 p < 0.05), sedation (β = 2.38, p < 0.05), and craving (β = 3.28, p < 0.001) in the laboratory, and drinking outcomes in RCTs, such that medications that reduced stimulation, sedation, and craving during the alcohol administration were associated with better clinical outcomes.  These results apply to alcohol administration phenotypes and may be especially useful to medications for which the mechanisms of action involve alterations in subjective responses to alcohol (e.g., antagonist medication).

These methods and results can be applied to a host of clinical questions and can streamline the process of screening novel compounds for AUD. For instance, this approach can be used to quantify the predictive utility of cue-reactivity screening models and even preclinical models of medication development.

Ref: https://www.nature.com/articles/s41386-020-00913-3