In the past 12 years, we have learned that: a) ondansetron, a serotonin-3 receptor antagonist, is efficacious treatment for alcohol dependence among alcohol-dependent adults who develop problem drinking before the age of 25 years (i.e., early-onset alcoholics);b) alcohol-dependent adolescents reduce their drinking markedly following ondansetron treatment, and c) alcoholics who are homozygous for the long polymorphic form (LL) of the serotonin transporter (5-HTT) allele experience greater reduction in severe drinking following ondansetron treatment than those who are homozygous for the short form (SS) or heterozygous for the long form (SL) of the 5-HTT allele. Ondansetron is, therefore, suited uniquely to enhancing current treatment approaches for severe or binge drinking among emerging (18- to 25-year-old) adults, especially those with the LL genotype. Whilst the mainstay of individual-focused interventions for emerging adults has been to provide brief motivational interventions such as the BASICS program to increase awareness of drinking consequences and readiness for change for reducing severe or binge drinking, many participants do not progress to the action phase of readiness to quit and continue to drink at hazardous levels. We, therefore, plan to apply what we have learned over the last 12 years to test the hypothesis that ondansetron plus our adapted version of BASICS (BASICS Plus) will be more efficacious than BASICS Plus alone at reducing severe or binge drinking, especially among emerging adults with the LL genotype. We also shall test the additional hypothesis that ondansetron adds to the therapeutic benefit of BASICS Plus even in those with lower readiness for change. The study design will be a randomized, double-blind, placebo-controlled trial in which emerging adults will receive 1 week of single-blind placebo followed by 8 weeks of ondansetron + BASICS Plus or 1 week of single-blind placebo followed by 8 weeks of placebo + BASICS Plus. Each treatment group shall contain 150 individuals (total N=300), stratified into two equal subgroups of those who are LL vs. Sx (i.e., LS or SS) for the 5-HTT allele. This innovative and significant study is designed to develop an efficacious pharmacotherapeutic and pharmacogenetic approach that can enhance the efficacy of a brief intervention to treat severe drinking in emerging adults.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
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Roach, Deidra
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University of Virginia
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Johnson, Bankole A (2017) Toward Rational, Evidence-Based, and Clinically Relevant Measures to Determine Improvement Following Treatment for Alcohol Use Disorder. Alcohol Clin Exp Res 41:703-707
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