Mechanisms of Naltrexone Action on Drinking in Adolescents

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DESCRIPTION (provided by applicant): Adolescent alcohol misuse is a serious public health concern and there is a clear need for effective alcohol treatment for youth. Naltrexone (NTX) has been shown to be efficacious for reducing drinking rates among adults with alcohol dependence (AD) in approximately 25 controlled clinical trials. However, to date only two case reports, one open-label study, and one double-blind randomized trial have examined the usefulness of NTX for adolescents with AD. Although these reports suggest that NTX reduces drinking in youth by attenuating craving, no controlled laboratory studies have assessed craving or other putative mechanisms of NTX action on drinking in adolescents. This major purpose of the proposed exploratory study (R21) is to provide important new information about the mechanisms of NTX action in adolescents while establishing the utility of a comprehensive yet efficient paradigm for studying mechanisms of pharmacotherapy action in youth. Ninety non-treatment seeking adolescents with AD (ages 15 to 18) will participate in a randomized, double-blind, placebo-controlled, between-subjects study. The effects of NTX on alcohol cueinduced craving will be assessed using our human laboratory cue reactivity paradigm. In addition, the effects of NTX on the subjective rewarding/stimulatory and dysphoric effects of alcohol consumption will be assessed in the natural environment using an ecological momentary assessment approach by having teenagers use handheld electronic diaries to monitor their drinking, craving, and the subjective effects of alcohol ingestion for 10-days. Understanding how particular medications may reduce drinking would allow for a more targeted pharmacotherapeutic approach to treatment and inform which combinations of medications may be most beneficial for treating AD among youth.