The Feasibility, Tolerability, and Safety of Administering a Very High Alcohol Dose to Drinkers with Alcohol Use Disorder.

INTRODUCTION There remains a paucity of research quantifying alcohol's effects in drinkers with alcohol use disorder (AUD), particularly responses to very high alcohol doses (≥0.8 g/kg). As drinkers with AUD frequently engage in very heavy drinking (8-10 drinks/occasion), doses of ≤ 0.8 g/kg may lack ecological validity. The present study examined the feasibility, tolerability, and safety of administering a very high alcohol dose (1.2 g/kg) to non-treatment seeking AUD participants. METHODS Sixty-one young-adult AUD drinkers enrolled in the Chicago Social Drinking Project and completed three laboratory sessions at which they consumed a beverage with 1.2 g/kg, 0.8 g/kg, and 0.0 g/kg alcohol. Physiological responses (vital signs, nausea and vomiting, breath alcohol concentrations (BrAC)) were monitored throughout the sessions. After each session, participants completed a next-day survey of substance use, engagement in risky behaviors, and related consequences. RESULTS Overall, the sample demonstrated good compliance with study procedures; 93% of participants adhered to pre-session alcohol abstinence requirements (indicated by BrAC < 0.003 g/dL), with no participants exhibiting serious alcohol withdrawal symptoms at arrival to study visits. The 1.2 g/kg alcohol dose achieved an expected mean peak BrAC of 0.13 g/dL at 60-minutes after drinking, which was well-tolerated; the majority of the sample did not experience nausea (70%) or vomiting (93%), and dose effects on vital signs were not clinically significant. Finally, we demonstrated that the 1.2g/kg alcohol dose is safe and not associated with post-session consequences, including reduced sleep time, atypical substance use, accidents or injuries, and severe hangovers. CONCLUSION Results support the feasibility, tolerability, and safety of administering a very high alcohol dose to young adult drinkers with AUD within the context of a well-validated laboratory alcohol challenge paradigm. Utilizing an alcohol dose more consistent with naturalistic drinking patterns may foster greater ecological validity of laboratory paradigms for persons with moderate to severe AUD.

[1]  H. Dewit,et al.  Subjective Responses to Alcohol in the Development and Maintenance of Alcohol Use Disorder. , 2021, The American journal of psychiatry.

[2]  S. O'Malley,et al.  Effects of Alcohol Cue Reactivity on Subsequent Treatment Outcomes among Treatment-Seeking Individuals with Alcohol Use Disorder: A Multisite Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Varenicline. , 2020, Alcoholism, clinical and experimental research.

[3]  Melissa A. Cyders,et al.  To Infuse or Ingest in Human Laboratory Alcohol Research. , 2020, Alcoholism, clinical and experimental research.

[4]  Daniel J Fridberg,et al.  Real-Time Mobile Monitoring of Drinking Episodes in Young Adult Heavy Drinkers: Development and Comparative Survey Study , 2019, JMIR mHealth and uHealth.

[5]  M. Schwandt,et al.  Exogenous ghrelin administration increases alcohol self-administration and modulates brain functional activity in heavy-drinking alcohol-dependent individuals , 2018, Molecular Psychiatry.

[6]  H. de Wit,et al.  Striatal activity correlates with stimulant-like effects of alcohol in healthy volunteers , 2018, Neuropsychopharmacology.

[7]  Michael D. Justiss,et al.  Alcohol intoxication progressively impairs drivers' capacity to detect important environmental stimuli , 2018, Pharmacology Biochemistry and Behavior.

[8]  J. Jentsch,et al.  Differences in the subjective and motivational properties of alcohol across alcohol use severity: application of a novel translational human laboratory paradigm , 2018, Neuropsychopharmacology.

[9]  M. Sloan,et al.  Vulnerability for Alcohol Use Disorder and Rate of Alcohol Consumption. , 2017, The American journal of psychiatry.

[10]  L. Ray,et al.  Differences between treatment-seeking and non-treatment-seeking participants in medication studies for alcoholism: do they matter? , 2017, The American journal of drug and alcohol abuse.

[11]  V. Ramchandani,et al.  Drinking Motives Predict Subjective Effects of Alcohol and Alcohol Wanting and Liking During Laboratory Alcohol Administration: A Mediated Pathway Analysis. , 2016, Alcoholism, clinical and experimental research.

[12]  Dingcai Cao,et al.  A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder , 2016, Biological Psychiatry.

[13]  C. Enders,et al.  Contextual influences on subjective and behavioral responses to alcohol. , 2015, Experimental and clinical psychopharmacology.

[14]  M. Schwandt,et al.  Effects of naltrexone on neural and subjective response to alcohol in treatment-seeking alcohol-dependent patients. , 2014, Alcoholism, clinical and experimental research.

[15]  J. McGeary,et al.  Acute effects of low and high dose alcohol on smoking lapse behavior in a laboratory analogue task , 2014, Psychopharmacology.

[16]  Dingcai Cao,et al.  Alcohol Challenge Responses Predict Future Alcohol Use Disorder Symptoms: A 6-Year Prospective Study , 2014, Biological Psychiatry.

[17]  A. King,et al.  Acute alcohol response phenotype in heavy social drinkers is robust and reproducible. , 2014, Alcoholism, clinical and experimental research.

[18]  J. McGeary,et al.  A human laboratory pilot study with baclofen in alcoholic individuals , 2013, Pharmacology Biochemistry and Behavior.

[19]  M. Fillmore,et al.  Acute tolerance to alcohol in at-risk binge drinkers. , 2012, Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors.

[20]  Megan Conrad,et al.  Alternative substance paradigm: effectiveness of beverage blinding and effects on acute alcohol responses. , 2012, Experimental and clinical psychopharmacology.

[21]  U. Zimmermann,et al.  Modeling alcohol self-administration in the human laboratory. , 2011, Current topics in behavioral neurosciences.

[22]  Dingcai Cao,et al.  Rewarding, stimulant, and sedative alcohol responses and relationship to future binge drinking. , 2011, Archives of general psychiatry.

[23]  D. Hommer,et al.  A genetic determinant of the striatal dopamine response to alcohol in men , 2010, Molecular Psychiatry.

[24]  L. Ray,et al.  Catching the alcohol buzz: an examination of the latent factor structure of subjective intoxication. , 2009, Alcoholism, clinical and experimental research.

[25]  K. Mann,et al.  Offspring of parents with an alcohol use disorder prefer higher levels of brain alcohol exposure in experiments involving computer-assisted self-infusion of ethanol (CASE) , 2009, Psychopharmacology.

[26]  S. Minsky,et al.  The incidence and severity of hangover the morning after moderate alcohol intoxication. , 2008, Addiction.

[27]  W. Corbin,et al.  Stimulant alcohol effects prime within session drinking behavior , 2008, Psychopharmacology.

[28]  S. Minsky,et al.  The Acute Hangover Scale: A new measure of immediate hangover symptoms. , 2007, Addictive behaviors.

[29]  David Couper,et al.  Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. , 2006, JAMA.

[30]  D. Davidson,et al.  Does participation in an alcohol administration study increase risk for excessive drinking? , 2005, Alcohol.

[31]  L. Ray,et al.  A polymorphism of the mu-opioid receptor gene (OPRM1) and sensitivity to the effects of alcohol in humans. , 2004, Alcoholism, clinical and experimental research.

[32]  R. Anton,et al.  Naltrexone effects on alcohol consumption in a clinical laboratory paradigm: temporal effects of drinking , 2004, Psychopharmacology.

[33]  H. de Wit,et al.  Biphasic alcohol response differs in heavy versus light drinkers. , 2002, Alcoholism, clinical and experimental research.

[34]  P. Eastman.  Toll of Binge Drinking Far More Destructive than Realized: A study funded by the National Institute on Alcohol Abuse and Alcoholism found that about 40% of college students binge drink, and each year 1,400 die , 2002 .

[35]  Rajita Sinha,et al.  Naltrexone decreases craving and alcohol self-administration in alcohol-dependent subjects and activates the hypothalamo–pituitary–adrenocortical axis , 2002, Psychopharmacology.

[36]  R. Sinha,et al.  Naturalistic follow-up of drinking behavior following participation in an alcohol administration study. , 1999, Journal of Substance Abuse Treatment.

[37]  T. Babor,et al.  Ethical, scientific and clinical issues in ethanol administration research involving alcoholics as human subjects. , 1997, Addiction.

[38]  H. Wit,et al.  Effect of setting on the reinforcing and subjective effects of ethanol in social drinkers , 1995, Psychopharmacology.

[39]  H. de Wit,et al.  Ethanol self-administration in males with and without an alcoholic first-degree relative. , 1990, Alcoholism, clinical and experimental research.

[40]  C. Lieber,et al.  High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. , 1990, The New England journal of medicine.

[41]  C. Naranjo,et al.  Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). , 1989, British journal of addiction.

[42]  K. Sher.  Subjective effects of alcohol: the influence of setting and individual differences in alcohol expectancies. , 1985, Journal of studies on alcohol.

[43]  B. Tabakoff,et al.  Acute alcohol intoxication, mood states and alcohol metabolism in women and men , 1983, Pharmacology Biochemistry and Behavior.

[44]  N. Christensen,et al.  Ethanol metabolism in heavy drinkers after massive and moderate alcohol intake. , 1983, Biochemical pharmacology.

[45]  D. Sitar,et al.  Ethanol 'dose-dependent' elimination: Michaelis-Menten v classical kinetic analysis. , 1981, British journal of clinical pharmacology.

[46]  J. Mendelson,et al.  A quantitative analysis of drinking patterns in alcoholics. , 1971, Archives of general psychiatry.

[47]  J. Mendelson,et al.  EXPERIMENTAL ANALYSIS OF DRINKING BEHAVIOR OF CHRONIC ALCOHOLICS * , 1966, Annals of the New York Academy of Sciences.

[48]  J. Mendelson,et al.  Operant Analysis of Drinking Patterns of Chronic Alcoholics , 1965, Nature.

[49]  L. Ray,et al.  Alcohol use following an alcohol challenge and a brief intervention among alcohol-dependent individuals. , 2014, The American journal on addictions.

[50]  Jennifer E. Merrill,et al.  Mood and implicit alcohol expectancy processes: predicting alcohol consumption in the laboratory. , 2012, Alcoholism, clinical and experimental research.

[51]  Robert G. Hahn,et al.  Role of Variability in Explaining Ethanol Pharmacokinetics , 2003, Clinical pharmacokinetics.

[52]  R. Anton,et al.  Drinking in alcoholics following an alcohol challenge research protocol. , 2000, Journal of studies on alcohol.

[53]  Linda C. Sobell,et al.  Timeline Follow-Back A Technique for Assessing Self-Reported Alcohol Consumption , 1992 .

[54]  Charles E. McCulloch,et al.  Tests for Equality of Variances with Paired Data , 1987 .

[55]  W. Schofield.  Predicting basal metabolic rate, new standards and review of previous work. , 1985, Human nutrition. Clinical nutrition.

[56]  P. Watson,et al.  Total body water volumes for adult males and females estimated from simple anthropometric measurements. , 1980, The American journal of clinical nutrition.