Study strengths included a placebo-controlled prospective design with 624 individual laboratory sessions with alcohol and placebo conditions, excellent follow-up retention, and inclusion of a comparison low-risk group to account for general drift and temporal effects. Limitations included that the reexamination interval may not have been sufficient to observe the extent of neuroadaptative responses to alcohol(18) and beverages were consumed over short interval to capture direct alcohol effects and minimize variability but this may not translate to typical drinking situations. Further, trajectory analyses resulted in unequal subgroup sample sizes and participants under age 21 were not enrolled due to legal restrictions of alcohol administration in the U.S. precluding study of alcohol responses in earlier developmental periods. The results support prior work showing high alcohol-induced stimulation, reward, and craving in heavy drinkers or alcoholics(33, 79, 80) as well as low alcohol-induced sedation and cortisol in other at-risk drinkers(81). However, heavy drinkers have also shown reduced alcohol-related stimulation and ventral striatal brain activation relative to social drinkers(82). Significant methodological differences across studies, i.e., sample size, subject characteristics, alcohol dose, route of administration, and
