Mechanisms of Naltrexone Action on Drinking in Adolescents

描述（由申请人提供）：青少年酒精滥用是一个严重的公共卫生问题，显然需要对青少年进行有效的酒精治疗。在大约25项对照临床试验中，纳曲酮（NTX）已被证明对降低酒精依赖（AD）的成人饮酒率有效。然而，迄今为止，只有两个病例报告，一个开放标签研究和一个双盲随机试验检验了NTX对青少年AD的有效性。尽管这些报告表明，NTX通过减少渴望来减少青少年饮酒，但没有对照实验室研究评估青少年饮酒的渴望或其他假定的NTX作用机制。这项探索性研究（R21）的主要目的是提供有关青少年NTX作用机制的重要新信息，同时为研究青少年药物治疗作用机制建立一个全面而有效的范例。90名寻求非治疗的阿尔茨海默病青少年（15至18岁）将参加一项随机、双盲、安慰剂对照的受试者间研究。NTX对酒精线索诱导的渴望的影响将使用我们的人类实验室线索反应范式进行评估。此外，NTX对酒精消费的主观奖励/刺激和焦虑效应的影响将在自然环境中使用生态瞬时评估方法进行评估，通过让青少年使用手持电子日记监测他们的饮酒，渴望和酒精摄入的主观影响10天。了解特定药物是如何减少饮酒的，将有助于制定更有针对性的药物治疗方法，并告知哪种药物组合对治疗青少年阿尔茨海默病最有益。

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.