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Cited by 379Substance Abuse Treatment and OutcomesAlcohol Consumption and Health EffectsNeurotransmitter Receptor Influence on Behavior

Rewarding, stimulant, and sedative alcohol responses and relationship to future binge drinking

Open access
King, Andrea C., de Wit, Harriet, McNamara, Patrick J., Cao, Dingcai·2011·Archives of General Psychiatry
DOI 10.1001/archgenpsychiatry.2011.26PMC PMC4633413
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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, Timeline 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.

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Written from the paper’s full text.

TL;DR

In a 2-year prospective alcohol challenge study, heavy social drinkers showed greater stimulant/rewarding and lower sedative/cortisol responses to alcohol than light drinkers, and these acute responses predicted future binge drinking. The findings support revising low-level response theory and the differentiator model to include heightened rewarding/stimulant effects as predictors of alcohol problems.

Key findings

  • Heavy drinkers (HD) reported greater positive/rewarding effects and lower sedative/cortisol responses than light drinkers (LD); effect sizes were Cohen’s d=0.47 for stimulation, 0.46 for like, 0.53 for want more, 0.53 for sedation, and 0.36 for cortisol.
  • Among HD, high-dose alcohol responses predicted future binge drinking: greater like (r=+0.37; P<.001), greater want more (r=+0.38; P<.001), and lower sedation (r=−0.20; P<.05); low-dose like (r=+0.24; P<.05) and want more (r=+0.23; P<.05) were weaker predictors.
  • Greater liking (OR [SE], 29.81 [29.42]; P=.001) and wanting more (OR [SE], 7.43 [5.32]; P=.005) were associated with later alcohol use disorder diagnosis; when binge drinking pattern was included, associations were reduced (like: OR [SE], 14.64 [15.04]; P<.01; want more: OR [SE], 3.51 [2.64]; P=.10), suggesting partial or full mediation.
  • During follow-up, LD drank on 23% of days and binge drank on 1.4% of days, versus 46% and 26% for HD (P<.001); retention was 99.1% (1506/1520 quarterly follow-ups).

Methods

  • Within-subject, double-blind, placebo-controlled, multidose laboratory alcohol challenge with 3 randomized sessions: high dose (0.8 g/kg), low dose (0.4 g/kg), and placebo, followed by quarterly assessments for 2 years.
  • Participants were 190 completers aged 21–35: heavy drinkers (n=104 [44 women]) and light drinkers (n=86 [41 women]); 570 laboratory sessions were conducted.
  • Measures included the Biphasic Alcohol Effects Scale, Drug Effects Questionnaire, salivary cortisol, Timeline Follow-Back, Drinker Inventory of Consequences–Recent, and DSM-IV alcohol abuse/dependence; analyses used repeated-measures ANOVA, mixture modeling for drinking trajectories, linear trend analyses, generalized estimating equations, and mediational analysis.

Limitations

  • Stated: participants had to be at least 21 years old, so findings may not generalize to younger drinkers, especially ages 18–20 when binge drinking and alcohol use disorders are most prevalent.
  • Stated: participants’ average age was 25 years, often corresponding to 5–7 years of regular binge drinking, so it was not possible to determine whether alcohol responses were constitutional or acquired; the 2-year follow-up may also be too short for the full range of drinking and alcohol use disorders to emerge.
  • Evident: the sample was selected as high-risk heavy social drinkers and light-drinker controls rather than a general population sample, and the laboratory paradigm did not completely mimic all aspects of social drinking; the paper also notes the subgroup of sons of alcoholic fathers was relatively small, potentially reducing power to detect family-history effects.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1001/archgenpsychiatry.2011.26

Cites

101 of 101 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 49 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Greater frequency of binge drinking during follow-up was associated with greater likelihood of meeting diagnostic criteria for alcohol abuse and dependence.

    “In turn, greater frequency of binge drinking during follow-up was associated with greater likelihood of meeting diagnostic criteria for alcohol abuse and dependence.”
    • Also stated in: § DRINKING BEHAVIORS DURING THE FOLLOW-UP INTERVAL · plain
      “The distinction of these trajectory groups was supported by other alcohol-related outcomes during follow-up, including typical and maximal drinking quantity, alcohol-related consequences, and DSM-IV diagnoses of alcohol abuse and dependence (Table 3).”
    Quote in the paperSubstantial claim
  • Findingown data

    Alcohol produced greater stimulant responses in heavy drinkers compared with light drinkers, particularly during the ascending limb at the high dose.

    “Alcohol produced greater stimulant and rewarding (liking and wanting) responses and lower sedative and cortisol responses in heavy vs light drinkers.”
    • Also stated in: § ALCOHOL RESPONSE: HD VS LD · plain
      “High-dose alcohol significantly increased Biphasic Alcohol Effects Scale stimulation ratings in the HD vs the LD during the early, ascending limb of the BrAC (group×dose×time:F8,1504=3.21; P=.001)and both like and want more ratings throughout both limbs (group×dose: like, F2,376=15.68; P<.001; and want more, F2,376=12.04; P<.001).”
    Quote in the paperSubstantial claim
  • Findingown data

    Among heavy drinkers, greater positive effects (like and want more) and lower sedative effects after alcohol consumption predicted increased binge drinking frequency during follow-up.

    “Among the heavy drinkers, greater positive effects and lower sedative effects after alcohol consumption predicted increased binge drinking frequency during follow-up.”
    • Also stated in: § RELATIONSHIP OF ALCOHOL RESPONSE TO SUBSEQUENT DRINKING BEHAVIORS · hedged
      “For HD at the high dose, greater ratings of like(r=+0.37; P<.001) and want more (r=+0.38; P < .001) and lower ratings of sedation(r=−0.20;P<.05)were significantly linearly associated with subsequent drinking trajectory group, indicating an overall moderate effect (Figure 5).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 60-minute time point and high alcohol dose represent clinically relevant breath alcohol concentration levels, such as the US legal limit for intoxicated driving.
  • Findingown data

    In heavy drinkers at the high dose, greater ratings of like were significantly linearly associated with subsequent drinking trajectory group.

    “For HD at the high dose, greater ratings of like(r=+0.37; P<.001) and want more (r=+0.38; P < .001) and lower ratings of sedation(r=−0.20;P<.05)were significantly linearly associated with subsequent drinking trajectory group, indicating an overall moderate effect (Figure 5).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 60-minute time point and high alcohol dose represent clinically relevant breath alcohol concentration levels, such as the US legal limit for intoxicated driving.
  • Findingown data

    In heavy drinkers at the high dose, lower ratings of sedation were significantly linearly associated with subsequent drinking trajectory group.

    “For HD at the high dose, greater ratings of like(r=+0.37; P<.001) and want more (r=+0.38; P < .001) and lower ratings of sedation(r=−0.20;P<.05)were significantly linearly associated with subsequent drinking trajectory group, indicating an overall moderate effect (Figure 5).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 60-minute time point and high alcohol dose represent clinically relevant breath alcohol concentration levels, such as the US legal limit for intoxicated driving.
  • May combine two claims. 33
  • The quote only partly states this claim. 2
  • Classified as probably not a substantial claim. 17

  • May combine two claims.

    Findingown data

    Alcohol produced lower sedative responses in heavy drinkers compared with light drinkers, with light drinkers reporting higher sedation throughout both BrAC limbs after the high dose.

    “Alcohol produced greater stimulant and rewarding (liking and wanting) responses and lower sedative and cortisol responses in heavy vs light drinkers.”
    • Also stated in: § ALCOHOL RESPONSE: HD VS LD · plain
      “Increases in Biphasic Alcohol Effects Scale sedation were noted in both groups after alcohol consumption, with the LD reporting higher sedation than the HD throughout both BrAC limbs after the high dose (group×dose×time: F8,1504=4.87; P <.001; Figure 3A).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    Alcohol produced greater wanting (want more) responses in heavy drinkers compared with light drinkers, at both high and low doses.

    “Alcohol produced greater stimulant and rewarding (liking and wanting) responses and lower sedative and cortisol responses in heavy vs light drinkers.”
    • Also stated in: § ALCOHOL RESPONSE: HD VS LD · plain
      “The HD reported greater positive and rewarding subjective effects of alcohol than the LD, particularly at the high dose (Figure2A–C).”
    • Also stated in: § ALCOHOL RESPONSE: HD VS LD · plain
      “Furthermore, the low dose of alcohol also increased ratings for like and want more in the HD vs the LD(Figure2).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    Alcohol produced greater rewarding (like) responses in heavy drinkers compared with light drinkers, at both high and low doses.

    “Alcohol produced greater stimulant and rewarding (liking and wanting) responses and lower sedative and cortisol responses in heavy vs light drinkers.”
    • Also stated in: § ALCOHOL RESPONSE: HD VS LD · plain
      “The HD reported greater positive and rewarding subjective effects of alcohol than the LD, particularly at the high dose (Figure2A–C).”
    • Also stated in: § ALCOHOL RESPONSE: HD VS LD · plain
      “Furthermore, the low dose of alcohol also increased ratings for like and want more in the HD vs the LD(Figure2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Alcohol produced lower cortisol responses in heavy drinkers compared with light drinkers; increases in salivary cortisol were evident in light drinkers during the descending limb after the high dose, but there were no cortisol increases in heavy drinkers.

    “Alcohol produced greater stimulant and rewarding (liking and wanting) responses and lower sedative and cortisol responses in heavy vs light drinkers.”
    • Also stated in: § ALCOHOL RESPONSE: HD VS LD · plain
      “Increases in salivary cortisol levels were evident in the LD during the descending limb after the high dose, but there were no cortisol increases in the HD (group×dose×time: F8,1504 =6.03; P<.001; Figure 3B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Quarterly follow-ups revealed that 4 trajectory patterns best described the binge drinking patterns among heavy drinkers and 2 patterns best described the light drinkers.

    “Quarterly follow-ups revealed that 4 trajectory patterns best described the binge drinking patterns among HD and 2 patterns best described the LD (Table 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There were no significant effects of family history of alcoholism or interactions of family history and drinking group or family history and sex on alcohol response measures.

    “There were no significant effects of FH of alcoholism (F ≤ 1.27 for all; P ≥ .27 for all) or interactions of FH and drinking group (F ≤ 1.25 for all; P ≥.26 for all) or FH and sex (F ≤ 0.93 for all; P ≥.47 for all) on alcohol response measures.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The trajectory groups for light drinkers were non-binge (81.4%) and infrequent binge (18.6%); for heavy drinkers, exacerbating binge (6.7%), high-frequency binge (25.0%), moderate-frequency binge (59.6%), and gradual maturing binge (8.7%).

    “Figure 4 depicts the 2 trajectory groups for LD: non-binge (81.4%) and infrequent binge (18.6%) and, consistent with other studies,46,84–87 the 4 trajectory groups for HD: exacerbating binge (6.7%), high-frequency binge (25.0%), moderate-frequency binge (59.6%), and gradual maturing binge (8.7%).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    There was a trend for an interaction in men for want more ratings (family history×dose×time, F=2.03, P=.06), driven by higher ratings during placebo for men with positive family history vs men with negative family history.

    “However, there was a trend for an interaction in these men in ratings for want more (FH×dose×time, F=2.03, P=.06), which was driven by higher ratings during placebo for men with positive FH vs men with negative FH.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The magnitude of group differences on alcohol response change scores was moderate, with effect sizes (Cohen's d) of 0.47 for stimulation, 0.46 for like, 0.53 for want more, 0.53 for sedation, and 0.36 for cortisol.

    “The magnitude of the group differences on alcohol response change scores was moderate, with effect sizes computed by Cohen’s dequaling0.47 for stimulation, 0.46 for like, 0.53 for want more, 0.53 for sedation, and 0.36 for cortisol.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Alcohol dose-dependently increased self-report ratings of feel drug, with light drinkers more sensitive than heavy drinkers at the high dose.

    “Alcohol dose-dependently increased self-report ratings of feel drug (Figure 1B), with the LD more sensitive than the HD at the high dose of alcohol (group×dose×time: F6,1128=4.57; P<.001).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In heavy drinkers, low-dose want more ratings were also predictive of drinking trajectory group, but the association was weaker than for the high dose.

    “Ratings at the low alcohol dose for like(r=+0.24;P<.05) and want more (r=+0.23; P<.05) were also predictive of drinking trajectory group, but the association was weaker than for the high dose.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 60-minute time point and high alcohol dose represent clinically relevant breath alcohol concentration levels, such as the US legal limit for intoxicated driving.

  • May combine two claims.

    Findingown data

    Although disinhibited personality and family history (FH) predicted future drinking in HD, controlling for these factors did not alter the relationships between alcohol responses and subsequent drinking behavior.

    “Although disinhibited personality and FH predicted future drinking in HD, controlling for these factors did not alter the relationships between alcohol responses and subsequent drinking behavior.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    HD report greater acute subjective positive effects and lesser sedative and cortisol response to an intoxicating dose of alcohol than do LD.

    “We have replicated and extended our group’s prior preliminary findings20,21 demonstrating that HD report greater acute subjective positive effects and lesser sedative and cortisol response to an intoxicating dose of alcohol than do LD.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [20] Holdstock L King AC de Wit H Subjective and objective responses to ethanol in moderate/heavy and light social drinkers Alcohol Clin Exp Res 2000 24 6 789 794 10888066

      Not checked in the free run.

    • cites [21] King AC Houle T de Wit H Holdstock L Schuster A Biphasic alcohol response differs in heavy versus light drinkers Alcohol Clin Exp Res 2002 26 6 827 835 12068251

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Alcohol markedly increased positive-like effects during ascending to peak BrAC in HD, and these responses also predicted future drinking.

    “However, alcohol markedly increased positive-like effects during ascending to peak BrAC in this group, and these responses also predicted future drinking.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In heavy drinkers (HD), greater alcohol stimulation, greater liking, greater wanting, and lower sedation at the high dose predicted greater binge drinking frequency during follow-up (P < .001 for all).

    “Analyses using the generalized estimation equations approach confirmed that in HD, greater alcohol stimulation, greater liking, greater wanting, and lower sedation at the high dose predicted greater binge drinking frequency during follow-up (P < .001 for all).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In composite generalized estimation equations models including all significant alcohol responses, greater alcohol stimulation (P<.05), greater liking (P<.001), and lower sedation (P<.05) for the high dose remained significant predictors of future drinking.

    “Composite generalized estimation equations models that included all the significant alcohol responses indicated that greater alcohol stimulation (P<.05), greater liking (P<.001), and lower sedation (P<.05)for high dose remained significant predictors of future drinking.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For HD, increases in liking (OR [SE], 29.81 [29.42]; P=.001) and want more (OR [SE], 7.43 [5.32]; P=.005) were significantly associated with alcohol use disorder diagnosis during follow-up.

    “For HD, increases in liking(odds ratio[OR]{SE},29.81{29.42};P=.001) and want more (OR [SE],7.43 [5.32]; P=.005) were significantly associated with alcohol use disorder diagnosis during follow-up.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Greater liking and wanting responses to the low dose of alcohol also related to future binge drinking, but these relationships were not as strong as those observed with the high dose.

    “Greater liking and wanting responses to the low dose of alcohol also related to future binge drinking, but again these were not as strong as those observed with the high dose.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In heavy drinkers, low-dose like ratings were also predictive of drinking trajectory group, but the association was weaker than for the high dose.

    “Ratings at the low alcohol dose for like(r=+0.24;P<.05) and want more (r=+0.23; P<.05) were also predictive of drinking trajectory group, but the association was weaker than for the high dose.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 60-minute time point and high alcohol dose represent clinically relevant breath alcohol concentration levels, such as the US legal limit for intoxicated driving.

  • May combine two claims.

    Findingnone given

    For LD, an intoxicating dose of alcohol produces tired and sluggish feelings and activates release of the stress hormone cortisol.

    “For LD, an intoxicating dose of alcohol produces tired and sluggish feelings and activates release of the stress hormone cortisol.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    HD consume more alcohol overall (typical frequency, quantity, and maximum quantity) and experience clinically relevant outcomes, such as greater alcohol consequences and higher rates of DSM-IV alcohol use disorders, than LD.

    “They also consume more alcohol overall (typical frequency, quantity, and maximum quantity) and experience clinically relevant outcomes, such as greater alcohol consequences and higher rates of DSM-IV alcohol use disorders (Table 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    HD showed a variety of drinking trajectories during the 2 years of follow-up, and those experiencing less positive and more sedative acute alcohol effects gradually matured out of binge drinking over time.

    “In contrast, HD showed a variety of drinking trajectories during the 2 years of follow-up, and those experiencing less positive and more sedative acute alcohol effects gradually matured out of binge drinking over time.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    On the descending limb, liking (P<.001), wanting (P<.01), and less sedation (P<.01) predicted future drinking.

    “on the descending limb, liking (P<.001), wanting (P<.01), and less sedation (P<.01) predicted future drinking.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The heavy and light drinker groups were similar on most demographic characteristics.

    “The groups were similar on most demographic characteristics (Table 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Some young adult binge drinkers progress to become problem drinkers, whereas others reduce their consumption during middle and later adulthood.

    “For reasons that are not understood, some young adult binge drinkers progress to become problem drinkers, whereas others reduce their consumption during middle and later adulthood.39–46”
    Quote in the paperSubstantial claim0 of 8 sources checked
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      Not checked in the free run.

    • cites [40] Chassin L Pitts SC Prost J Binge drinking trajectories from adolescence to emerging adulthood in a high-risk sample: predictors and substance abuse outcomes J Consult Clin Psychol 2002 70 1 67 78 11860058

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    • cites [41] Dawson DA Grant BF Stinson FS Chou PS Toward the attainment of low-risk drinking goals: a 10-year progress report Alcohol Clin Exp Res 2004 28 9 1371 1378 15365308

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    • cites [45] Gruenewald PJ Russell M Light J Lipton R Searles J Johnson F Trevisan M Freudenheim J Muti P Carosella AM Nochajski TH One drink to a lifetime of drinking: temporal structures of drinking patterns Alcohol Clin Exp Res 2002 26 6 916 925 12068262

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    • cites [46] Schulenberg J O’Malley PM Bachman JG Wadsworth KN Johnston LD Getting drunk and growing up: trajectories of frequent binge drinking during the transition to young adulthood J Stud Alcohol 1996 57 3 289 304 8709588

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Among a sample of primarily young, white, male alcohol abusers, 46% remitted and no longer met criteria for an alcohol use disorder, 24% continued with alcohol abuse, and 30% progressed to alcohol dependence several years after an initial assessment.

    “Among a sample of primarily young, white, male alcohol abusers, Hasin and colleagues47 showed that several years after an initial assessment, 46% remitted and no longer met criteria for an alcohol use disorder, whereas 24% continued with alcohol abuse and 30% progressed to alcohol dependence.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Hasin DS Grant B Endicott J The natural history of alcohol abuse: implications for definitions of alcohol use disorders Am J Psychiatry 1990 147 11 1537 1541 2221170

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Individuals with a family history of alcoholism or frequent heavy drinking experience greater alcohol-induced positive-like subjective and objective effects.

    “However, there is also evidence inconsistent with the low-level response theory, suggesting instead that individuals with a FH of alcoholism or frequent heavy drinking experience greater alcohol-induced positive-like subjective and objective effects.7,18–25”
    Quote in the paperSubstantial claim0 of 9 sources checked
    • cites [7] Newlin DB Renton RM High risk groups often have higher levels of alcohol response than low risk: the other side of the coin Alcohol Clin Exp Res 2010 34 2 199 202 19951303

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    • cites [19] Erblich J Earleywine M Behavioral undercontrol and subjective stimulant and sedative effects of alcohol intoxication: independent predictors of drinking habits? Alcohol Clin Exp Res 2003 27 1 44 50 12544004

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    • cites [20] Holdstock L King AC de Wit H Subjective and objective responses to ethanol in moderate/heavy and light social drinkers Alcohol Clin Exp Res 2000 24 6 789 794 10888066

      Not checked in the free run.

    • cites [21] King AC Houle T de Wit H Holdstock L Schuster A Biphasic alcohol response differs in heavy versus light drinkers Alcohol Clin Exp Res 2002 26 6 827 835 12068251

      Not checked in the free run.

    • cites [22] Finn PR Pihl RO Men at high risk for alcoholism: the effect of alcohol on cardiovascular response to unavoidable shock J Abnorm Psychol 1987 96 3 230 236 3680762

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    • cites [24] Peterson JB Pihl RO Gianoulakis C Conrod P Finn PR Stewart SH LeMarquand DG Bruce KR Ethanol-induced change in cardiac and endogenous opiate function and risk for alcoholism Alcohol Clin Exp Res 1996 20 9 1542 1552 8986201

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    • cites [25] Morean ME Corbin WR Subjective response to alcohol: a critical review of the literature Alcohol Clin Exp Res 2010 34 3 385 395 20028359

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  • Classified as probably not a substantial claim.

    Premisecitation

    Stimulant responses to alcohol may lead to greater acute alcohol consumption.

    “Although there has been initial support for the differentiator model7 and although stimulant responses to alcohol may lead to greater acute alcohol consumption,26–30 thus far studies have been limited by modest sample sizes and cross-sectional designs.”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [26] Corbin WR Gearhardt A Fromme K Stimulant alcohol effects prime within session drinking behavior Psychopharmacology (Berl) 2008 197 2 327 337 18084744 PMC3039601

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    • cites [27] DeWit H Pierri J Johanson CE Assessing individual differences in ethanol preference using a cumulative dosing procedure Psychopharmacology (Berl) 1989 98 1 113 119 2498954

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    • cites [28] de Wit H Uhlenhuth EH Pierri J Johanson CE Individual differences in behavioral and subjective responses to alcohol Alcohol Clin Exp Res 1987 11 1 52 59 3551664

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    • cites [29] Ray LA Miranda R Jr Tidey JW McGeary JE MacKillop J Gwaltney CJ Rohsenow DJ Swift RM Monti PM Polymorphisms of the μ-opioid receptor and dopamine D4 receptor genes and subjective responses to alcohol in the natural environment J Abnorm Psychol 2010 119 1 115 125 20141248 PMC3703617

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    • cites [30] Wetherill RR Fromme K Subjective responses to alcohol prime event-specific alcohol consumption and predict blackouts and hangover J Stud Alcohol Drugs 2009 70 4 593 600 19515300 PMC2696300

      Not checked in the free run.

    • Rests on an assumption: Prior studies of acute alcohol responses and future drinking problems have been limited by modest sample sizes and cross-sectional designs.

  • May combine two claims.

    Premisecitation

    The only longitudinal study examining the role of acute alcohol responses to future drinking problems was conducted more than 15 years ago by Schuckit and Smith, and the alcohol responses measured were primarily negative intoxicating effects.

    “In fact, the only longitudinal study examining the role of acute alcohol responses to future drinking problems was conducted more than 15 years ago by Schuckit and Smith,8 and the alcohol responses measured were primarily negative intoxicating effects.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Schuckit MA Smith TL An 8-year follow-up of 450 sons of alcoholic and control subjects Arch Gen Psychiatry 1996 53 3 202 210 8611056

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    The Biphasic Alcohol Effects Scale has shown good reliability and validity and yields 2 subscales, stimulation and sedation, shown to correspond to alcohol effects often observed on ascending and descending breath alcohol concentrations, respectively.

    “The Biphasic Alcohol Effects Scale has shown good reliability and validity and yields 2 subscales, stimulation and sedation, shown to correspond to alcohol effects often observed on ascending and descending BrAC, respectively.68”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Martin CS Earleywine M Musty RE Perrine MW Swift RM Development and validation of the Biphasic Alcohol Effects Scale Alcohol Clin Exp Res 1993 17 1 140 146 8452195

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The low-level response theory posits that less intense alcohol responses may be associated with insensitivity to internal cues and warning signs to stop drinking, resulting in excessive consumption.

    “These findings have been cited as support for the low-level response theory articulated by Schuckit,17 which posits that less intense alcohol responses may be associated with insensitivity to internal cues and warning signs to stop drinking, resulting in excessive consumption.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Schuckit MA Self-rating of alcohol intoxication by young men with and without family histories of alcoholism J Stud Alcohol 1980 41 3 242 249 7374142

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    The differentiator model posits that high-risk persons have greater stimulant-like effects from alcohol during the early portion of a drinking episode, when breath alcohol concentrations are rising, and less sedative-like effects when breath alcohol concentrations are decreasing.

    “To resolve this apparent inconsistency, Newlin and Thomson6 proposed the differentiator model, which posits that high-risk persons have greater stimulant-like effects from alcohol during the early portion of a drinking episode, when breath alcohol concentrations (BrAC) are rising, and less sedative-like effects when BrAC are decreasing.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6] Newlin DB Thomson JB Alcohol challenge with sons of alcoholics: a critical review and analysis Psychol Bull 1990 108 3 383 402 2270234

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Session order did not affect the main results.

    “Session order did not affect the main results (F ≥ 3.20 for all; P < .001 for all).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    The heavy drinkers had fewer years of education and higher disinhibited personality trait scores than the light drinkers, both of which were included as covariates in all analyses.

    “The HD also had fewer years of education and higher disinhibited personality trait scores than the LD, both of which were included as covariates in all analyses.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Linear trend analyses controlled for the main sociodemographic risk factors associated with alcohol misuse by including them as covariates.

    “These analyses controlled for the main sociodemographic risk factors associated with alcohol misuse by including them as covariates.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The cortisol assay had inter- and intra-assay coefficients of variation of 6.88% and 7.12%, respectively.

    “The inter- and intra-assay coefficients of variation were 6.88% and 7.12%, respectively.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The modified Biphasic Alcohol Effects Scale instructions were validated in a previous report.

    “As validated in a previous report,70 we modified the original Biphasic Alcohol Effects Scale instructions so as not to divulge beverage contents, and we administered the scale at predrink baseline.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [70] Rueger SY McNamara PJ King AC Expanding the utility of the Biphasic Alcohol Effects Scale (BAES) and initial psychometric support for the Brief-BAES (B-BAES) Alcohol Clin Exp Res 2009 33 5 916 924 19320625 PMC2856649

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    Although heavy drinkers exhibited higher breath alcohol concentrations at the high dose than light drinkers, the difference was small, and covarying for breath alcohol concentration did not alter the main findings.

    “Although the HD exhibited higher BrAC at the high dose than did the LD (group×dose×time: F5,940=3.43; P<.01; Figure 1A), the difference between groups was small (range, 0.001–0.008 mg/L at various time points), and covarying for BrAC did not alter the main findings.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The breath alcohol concentration changes over time confirmed the expected pattern of ascending and descending limbs.

    “In the laboratory sessions, the BrAC changes over time confirmed the expected pattern of ascending and descending limbs.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Participants were randomized to dose order and tested under double-blind conditions.

    “Participants were randomized to dose order and tested under double-blind conditions.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Expectancies were minimized by blinding beverage content.

    “expectancies were minimized by blinding beverage content”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Binge drinking partially (for liking) or fully (for want more) mediated the relationship between alcohol response and subsequent alcohol use disorder.

    “suggesting that binge drinking partially (like) or fully (want more)mediated the relationship between alcohol response and subsequent alcohol use disorder.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    The study used a within-subjects, dose-ranging, and placebo-controlled design with intensive follow-up.

    “There were several strengths of this study, including the use of a within-subjects, dose-ranging, and placebo-controlled design with intensive follow-up.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The length of the follow-up interval may not have been adequate for the full range of drinking and related alcohol use disorders to emerge.

    “Finally, although the quarterly follow-up assessments after the laboratory sessions were sufficiently frequent to show fluctuations in drinking for 2 years, the length of this interval may not have been adequate for the full range of drinking and related alcohol use disorders to emerge.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The study was limited by the legal requirement that participants be a minimum of 21 years old to be given alcohol, so it is unclear whether the findings can be generalized to even younger drinkers.

    “The study was limited by the legal requirement that participants be a minimum of 21 years old to be given alcohol, so it is unclear whether the findings can be generalized to even younger drinkers.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Drinking outcomes were validated by assessment of alcohol consequences and DSM-IV diagnoses.

    “Drinking outcomes were validated by assessment of alcohol consequences and DSM-IV diagnoses.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    HD with heightened rewarding effects of alcohol perpetuated and increased binge drinking frequency over time, thereby increasing the likelihood of meeting DSM-IV diagnoses of alcohol abuse and dependence.

    “On the other hand, HD with heightened rewarding effects of alcohol perpetuated and increased binge drinking frequency over time, thereby increasing the likelihood of meeting DSM-IV diagnoses of alcohol abuse and dependence.”
    Quote in the paperSubstantial claim
47 of 47

  • The paper relies on this without support.

    Prior studies of acute alcohol responses and future drinking problems have been limited by modest sample sizes and cross-sectional designs.

    “Although there has been initial support for the differentiator model7 and although stimulant responses to alcohol may lead to greater acute alcohol consumption,26–30 thus far studies have been limited by modest sample sizes and cross-sectional designs.”

  • The paper relies on this without support.

    The 60-minute time point and high alcohol dose represent clinically relevant breath alcohol concentration levels, such as the US legal limit for intoxicated driving.

    “The main calculations were based on scores at 60 minutes (peak BrAC) and for the high dose because this time point and dose level produced consistent changes on study measures and represent clinically relevant BrAC levels, ie, the US legal limit for intoxicated driving.”

  • The paper relies on this without support.

    The low-level response theory and differentiator model are widely held.

    “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.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In heavy drinkers, greater alcohol stimulation and reward and lower sedation predicted binge drinking escalations at two-year follow-up.

    “Further, in heavy drinkers, greater alcohol stimulation and reward and lower sedation predicted binge drinking escalations at two-year follow-up(29), with greater stimulation and reward predicting more AUD symptoms experienced through six years(34).”

    From A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder (2016) · cites this paper as [29]

  • Compared with light drinkers, heavy drinkers exhibited higher alcohol sensitivity in subjective stimulation and reward (liking and wanting), as well as lower sensitivity in subjective sedation and salivary cortisol reactivity.

    “Our previously published results showed that compared with light drinkers, heavy drinkers exhibited both higher alcohol sensitivity, in terms of subjective stimulation and reward (liking and wanting)(29), as well as lower sensitivity, in terms of subjective sedation(29), and salivary cortisol reactivity(29, 32).”

    From A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder (2016) · cites this paper as [29]

  • Human studies in this area have been limited to retrospective patient reports, post mortem brain tissue methods, or cross-sectional laboratory paradigms, none of which directly measure alcohol responses in the same individuals over time.

    “Human studies in this area have been limited to retrospective patient reports(23), post mortem brain tissue methods(24), or cross-sectional laboratory paradigms(2, 3, 25–29), none of which directly measure alcohol responses in the same individuals over time.”

    From A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder (2016) · cites this paper as [29]

  • Previous studies relying on proxy measures of brain-behavior relationships to alcohol response have not been able to address within-person changes or stabilization in alcohol response over time.

    “Previous studies relying on proxy measures of brain-behavior relationships to alcohol response(2, 3, 23–29) have not been able to address within-person changes or stabilization in alcohol response over time.”

    From A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder (2016) · cites this paper as [29]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Wanting is called an independent predictor despite being absent from the composite model results

    Major

    The discussion says wanting more was a significant independent predictor in multivariate models. The results say that, after the significant alcohol responses were included together, stimulation, liking, and lower sedation remained significant predictors-not wanting more.

  • Ascending-limb change score uses an unlisted assessment time

    Minor

    The methods say ascending-limb change scores used a 15-minute time point, but the stated postbeverage assessment times begin at 30 minutes. No 15-minute assessment is listed.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. [59]First MB Spitzer RL Gibbon M Williams JBW Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition (SCID-I/P) New York, NY Biometrics Research, New York State Psychiatric Institute 2002

Cited by

Sorted by citations

Related

Authors
King, A. C., de Wit, H., McNamara, P. J., & Cao, D.
Affiliations
University of Chicago (US)
ORCID
Venue
Archives of General Psychiatry
Publisher
American Medical Association (AMA)
Published
2011-04-04
Volume
68
Issue
4
Pages
389
ISSN
0003-990X (ISSN-L)
DOI
10.1001/archgenpsychiatry.2011.26
PMC
PMC4633413
OpenAlex
W2126586632
Semantic Scholar
d4c78102f4a73f0b173031789daaf69184682625
Cited by
379
References
101
Citations by year
2026: 19 · 2025: 15 · 2024: 21 · 2023: 31 · 2022: 19 · 2021: 19 · 2020: 32 · 2019: 19 · 2018: 23 · 2017: 26 · 2016: 32 · 2015: 27 · 2014: 32 · 2013: 31 · 2012: 22
FWCI
22.80
Type
journal article
Language
en
Open access
Locations
  • Archives of General Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Alcohol Abuse and Alcoholism (R01AA013746)
  • National Institute on Drug Abuse (R01DA002812)
  • National Cancer Institute (P30‐CA14599, P30CA014599)
  • National Center for Research Resources (UL1RR024999)
Topics
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
binge drinking, acute alcohol effects, stimulant effects, sedative effects, cortisol response, alcohol craving, alcohol abuse, alcoholism
MeSH terms
Adult, Alcohol Drinking, Ethanol, Alcoholism, Breath Tests, Female, Humans, Hydrocortisone, Hypnotics and Sedatives, Male, Reward, Saliva

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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