Despite numerous strengths in this study, including placebo-controlled assessment of alcohol responses, repeated follow-ups, and successful retention (98%), there are several limitations worth noting. First, light social drinkers were enrolled originally as a control group, but they were not appropriate for testing of the models in this study. Their drinking over follow-up remained light (51), and analyses of the prospective role of alcohol response to future drinking and alcohol problems were not significant, likely due to limited target behavior to detect. Although some light drinkers showed positive-like alcohol responses, as a group, their predominantly high sedative alcohol responses appear to protect against alcohol problem development in adulthood in addition to other psychosocial factors that may have mitigated their risk for heavy drinking (52,53). Second, whether the observed alcohol responses were inherent or if they were acquired or sensitized over time in our sample with repeated binge-drinking exposures in early adulthood remains unknown. Unfortunately, for ethical reasons, alcohol challenge cannot be conducted in the United States in persons under age 21 to address this issue. Third, participants’ actual in vivo alcohol
