Rewarding, Stimulant, and Sedative Alcohol Responses and Relationship to Future Binge Drinking

Abstract

Context 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. Objective To prospectively assess the relationship of acute alcohol responses to future binge drinking. Design 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. Setting Participants recruited from the community. Participants 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). Intervention We conducted 570 laboratory sessions with a subsequent 99.1% follow-up (1506 of 1520). Main Outcome Measures Biphasic Alcohol Effects Scale, Drug Effects Questionnaire, cortisol response, Time-line Follow-Back, Drinker Inventory of Consequences–Recent, and DSM-IV alcohol abuse and dependence. Results 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. Conclusions 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. Trial Registration clinicaltrials.gov Identifier: NCT00961792

Negative affect is associated with alcohol, but not cigarette use in heavy drinking smokers

“…In partial agreement with the differentiator model (Newlin and Thomson, 1990), recent studies have found that lower sedative response and greater stimulant response to alcohol in the lab are associated with escalate drinking and AUD symptomatology at 2 (King et al, 2011) and even 6 years post assessment . Behavioral pharmacology studies have also established SR to be highly a reliable (Roche et al, 2013) and multi-dimensional phenotype consisting of stimulation, sedation and tension relief dimensions (Ray et al, 2009).…”

“…To that end, human research has demonstrated that individuals vary dramatically in their subjective response to alcohol (SR) and that these differences are in turn predictive of one's liability for alcoholism (King et al, 2011Ray et al, 2010b;Schuckit, 1984;Schuckit and Smith, 1996). In partial agreement with the differentiator model (Newlin and Thomson, 1990), recent studies have found that lower sedative response and greater stimulant response to alcohol in the lab are associated with escalate drinking and AUD symptomatology at 2 (King et al, 2011) and even 6 years post assessment .…”

“…In light of the multidimensionality of SR, the present study aims to simultaneously characterize these three key dimensions of SR (Ray et al, 2009). Thus SR, which is often in the human literature thought of as a marker of risk for future alcohol dependence (e.g., King et al, 2011;Schuckit, 1994) will serve as a biobehavioral marker of disease progression used to test neurobiologically informed predictions regarding the association between SR and motivation for alcohol during the transition from heavy drinking to alcohol dependence.…”

Reduced Subjective Response to Acute Ethanol Administration Among Young Men with a Broad Bipolar Phenotype

“…The 'differentiator' model proposes that individuals at-risk for AUDs experience enhanced stimulant effects during the ascending limb of the blood alcohol curve and diminished sedative effects during the descending limb (reviewed in Ray et al, 2010;Newlin and Thompson, 1990;Newlin and Renton, 2010). Although there remains some uncertainty about which precise dimension of individuals' subjective reactions to alcohol is most predictive of subsequent AUDs (King et al, 2002(King et al, , 2011, there is consensus that some aspect of individual subjective response mediates the risk forFand development ofFAUDs, making such response profiles potentially interesting endophenotypes (Morean and Corbin, 2010;Ray et al, 2010).…”

Can alcohol make you happy? A subjective wellbeing approach

“…There has been a temptation to suggest that all of the pleasures of drinking come with 'moderate' consumption rather than intoxication, but the strong form of this claim has been subject to critique (Keane, 2009;Room, 2000). Instead, heavier drinkers report greater stimulant and lower sedative effects (King et al, 2011), and people expect greater levels of both happiness and misery at higher levels of consumption (Adey et al, 2010).…”