1The Scripps Research Institute, La Jolla, CA
Advances in the neurobiology of alcohol dependence have highlighted an association between hyperactivation of stress systems in the CNS and drinking relapse risk during protracted withdrawal. A pharmacological strategy that facilitates homeostasis in stress systems dysregulated by drinking cessation may offer new treatment options for AUD. Screening such drug candidates in a validated human laboratory model of protracted withdrawal may increase the likelihood of selecting drugs that show efficacy in clinical trials. Data in support of the predictive validity of a human lab model of protracted withdrawal will be presented from a human lab study and an independent clinical trial of gabapentin, and a human lab study with post-treatment drinking data of a glucocorticoid antagonist (mifepristone) in volunteers with alcohol dependence. Data from these studies provide clinical validation of hyperactivation of central stress systems as a pharmacological treatment target, and support the predictive validity of a human lab model of risk factors for drinking relapse during protracted withdrawal in alcohol dependence.