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BACKGROUND: Subjective response to alcohol (SR), which reflects individual differences in sensitivity to the pharmacological effects of alcohol, may be an important endophenotype in understanding genetic influences on drinking behavior and alcohol use disorders (AUDs). SR predicts alcohol use and problems and has been found to differ by a range of established risk factors for the development of AUDs (e.g., family history of alcoholism). The exact pattern of SR associated with increased risk for alcohol problems, however, remains unclear. The Low Level of Response Model (LLR) suggests that high-risk individuals experience decreased sensitivity to the full range of alcohol effects, while the Differentiator Model (DM) asserts that high risks status is associated with increased sensitivity to alcohol's positive effects but decreased sensitivity to negative effects. AIMS: The current paper (1) reviews two prominent models of subjective response, (2) reviews extant laboratory-based research on subjective response, (3) highlights remaining gaps in our understanding and assessment of subjective response, and (4) encourages collaborative efforts to address these methodological and conceptual concerns. METHODS: This paper reviews studies which employed placebo-controlled and non-placebo-controlled alcohol challenge paradigms to assess a range of alcohol effects including impairment, stimulation, and sedation. RESULTS: The research literature provides at least partial support for both the LLR and DM models. High-risk individuals have been shown to have a reduced response to alcohol with respect to sedative or impairing effects, particularly on the descending limb of the blood alcohol curve (BAC). There is also evidence that ascending limb stimulant effects are more pronounced or operate differently for high-risk individuals. DISCUSSION: Despite commendable advances in SR research, important questions remain unanswered. Inconsistent results across studies may be attributable to a combination of an inadequate understanding of the underlying construct and methodological differences across studies (e.g., number and timing of assessments across the BAC, inclusion of a placebo condition). With respect to the underlying construct, existing measures fail to adequately distinguish between cognitive/behavioral impairment and sedation, aspects of which may be perceived positively (e.g., anxiolysis) due to their ability to act as negative reinforcers. CONCLUSIONS: Addressing the concerns raised by the current review will be integral to making meaningful scientific progress in the field of subjective response.
Morean et al. (Thu,) studied this question.