Mechanisms of Naltrexone Action on Drinking in Adolescents

说明(申请人提供)：青少年酗酒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)已被证明对降低成年酒精依赖(AD)患者的饮酒率有效。然而，到目前为止，只有两份病例报告、一项开放标签研究和一项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通过减轻渴望来减少青少年饮酒，但没有受控的实验室研究评估NTX对青少年饮酒的渴望或其他假定的机制。这项拟议的探索性研究(R21)的主要目的是提供有关NTX在青少年中作用机制的重要新信息，同时建立一个全面而有效的范例来研究青少年药物治疗的作用机制。90名未寻求治疗的阿尔茨海默病青少年(年龄从15岁到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求的影响将使用我们的人体实验室线索反应性范式进行评估。此外，NTX对酒精消费的主观奖励/刺激和烦躁影响的影响将在自然环境中使用生态瞬时评估方法进行评估，方法是让青少年使用手持电子日记监测他们的饮酒、渴望和10天酒精摄入的主观影响。了解特定药物如何减少饮酒将允许更有针对性的药物治疗方法，并告知哪些药物组合可能对治疗年轻人的AD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.