King AC, de Wit H, McNamara PJ, Cao D. Rewarding, stimulant, and sedative alcohol responses and relationship to future binge drinking. Arch Gen Psychiatry. 68: 389-399

Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, IL 60637, USA.
Archives of general psychiatry (Impact Factor: 14.48). 04/2011; 68(4):389-99. DOI: 10.1001/archgenpsychiatry.2011.26
Source: PubMed


Excessive consumption of alcohol is a major problem in the United States and abroad. Despite many years of study, it is unclear why some individuals drink alcohol excessively while others do not. It has been postulated that either lower or greater acute responses to alcohol, or both, depending on the limb of the breath alcohol concentration curve, contribute to propensity for alcohol misuse.
To prospectively assess the relationship of acute alcohol responses to future binge drinking.
Within-subject, double-blind, placebo-controlled, multidose laboratory alcohol challenge study with intensive follow-up. Each participant completed 3 randomized sessions examining responses to a high (0.8 g/kg) and low (0.4 g/kg) alcohol dose and placebo, followed by quarterly assessments for 2 years examining drinking behaviors and alcohol diagnoses.
Participants recruited from the community.
High-risk heavy social drinkers aged 21 to 35 years who habitually engage in weekly binge drinking (n = 104) and light drinker controls (n = 86).
We conducted 570 laboratory sessions with a subsequent 99.1% follow-up (1506 of 1520).
Biphasic Alcohol Effects Scale, Drug Effects Questionnaire, cortisol response, Timeline Follow-Back, Drinker Inventory of Consequences-Recent, and DSM-IV alcohol abuse and dependence.
Alcohol produced greater stimulant and rewarding (liking and wanting) responses and lower sedative and cortisol responses in heavy vs light drinkers. Among the heavy drinkers, greater positive effects and lower sedative effects after alcohol consumption predicted increased binge drinking frequency during follow-up. In turn, greater frequency of binge drinking during follow-up was associated with greater likelihood of meeting diagnostic criteria for alcohol abuse and dependence.
The widely held low level response theory and differentiator model should be revised: in high-risk drinkers, stimulant and rewarding alcohol responses even at peak breath alcohol concentrations are important predictors of future alcohol problems. Identifier: NCT00961792.

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    • "Sensitivity to the stimulant effects of alcohol is considered a risk factor for excessive alcohol consumption that may eventually lead to alcohol dependence (King et al., 2011, 2014). Therefore, the investigation of the stimulatory effects of alcohol is hoped to lead to the development of treatments or early interventions. "
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    • "The alcoholic beverage consisted of 16% volume ethanol, which contained 190-proof ethanol mixed with water, grape-flavored drink mix, and a sucralose-based sugar substitute. The alcohol dose was 0.8 g/kg, that is, equivalent to 4–5 standard alcohol drinks (King et al., 2011; Zhuang et al., 2012). The placebo beverage included 1% volume ethanol as a taste mask to reduce expectancy effects. "
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    • "Specifically, acute sedation may positively predict craving for alcohol within a given drinking episode, yet chronically heightened sedation may be protective in the long term. It is also possible that sedation on the descending limb, not the ascending limb, is protective against future dependence; however, longitudinal studies have shown sedation at peak BrAC to be as predictive of future dependence as descending limb sedation (King et al. 2014, 2011). Lastly, while the present results are in line with the differentiator model with respect to stimulation , the positive associations between SR and craving across both stimulation and sedation are more difficult to square with the LR model (Schuckit 1994). "
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