The role of brief potent glutamatergic modulation in addressing problem drinking: a randomized, controlled trial

项目总结： 谷氨酸神经递质的改变被认为是药物治疗的重要靶点 酒精使用障碍(AUD)。高效谷氨酸调节剂氯胺酮的初步研究 前额叶效应，提示亚麻醉剂的输注可能通过以下方式促进行为改变 解决各种物质使用障碍的严重脆弱性，包括澳门氏症。在基础上扩展 初步研究表明，氯胺酮联合应用可减少重度饮酒天数 通过动机增强疗法(MET)，这项为期12周的试验旨在检测比例差异 与我们之前的数据(n=120)一致的目的是评估氯胺酮是否促进HDD的减少 相对于主动控制(咪达唑仑)。我们将随机(1：1)120名寻求澳元病治疗的参与者 在两次注射氯胺酮或咪达唑仑时表现出高基线问题 每周(0.71 mg/kg氯胺酮或0.025 m/kg咪达唑仑52min)。此外，为了更严格地 评估行为治疗对氯胺酮疗效的影响，我们将采用2乘2因子 (2x2)设计，每个药物组的参与者随机(1：1)接受标准药物治疗 管理，或使用激励增强疗法(MET)的手册序列，然后 基于正念的复发预防(MBRP)。MBRP有望在以下情况下促进复发预防 在MET期间，个人已经减少了使用或开始禁欲。我们预测，与对照组相比， 咪达唑仑、氯胺酮会显著降低HDD患者的比例。一个重要的次要角色 假说是，那些接受氯胺酮和行为治疗的人会表现得明显更好 结果比单独接受氯胺酮的人要好。其他目的与氯胺酮对数字的影响有关 每日饮酒量和饮酒天数；氯胺酮对首次出现硬化症或辍学的时间的影响；以及 氯胺酮与MET/MBRP联合应用时的附加效果评价如果成功，这个项目 将对AUD的治疗做出重大贡献，针对AUD的新药物治疗策略是 需要的。未来的研究可能会使用这里介绍的设计来测试其他药物，并专注于 阐明氯胺酮治疗AUD的机制。 好了！

Project Summary: Alterations in glutamate neurotransmission are recognized as an important target of pharmacotherapy for alcohol use disorder (AUD). Preliminary investigations with ketamine, a glutamate modulator with potent prefrontal effects, suggest sub-anesthetic infusions may work to facilitate behavioral modification by addressing critical vulnerabilities for a variety of substance use disorders, including AUD. Expanding on a preliminary study suggesting that ketamine reduces number of heavy drinking days (HDD) when combined with motivational enhancement therapy (MET), this 12-week trial powered to detect proportional differences consistent with our prior data (n=120) aims to evaluate whether ketamine promotes a reduction in HDDs relative to an active control (midazolam). We will randomize (1:1) 120 participants seeking treatment for AUD and demonstrating high baseline problem drinking to 2 infusions of ketamine or midazolam separated by 5 weeks (0.71 mg/kg ketamine or 0.025 m/kg midazolam over 52 min). Further, in order to more rigorously assess the impact of behavioral treatment on the efficacy of ketamine, we will employ a two by two factorial (2x2) design, with participants in each medication arm randomized (1:1) either to standard medication management, or to a manualized sequence of motivational enhancement therapy (MET) followed by mindfulness-based relapse prevention (MBRP). MBRP is expected to facilitate relapse prevention after individuals have reduced use or initiated abstinence during MET. We predict that, compared to the control midazolam, ketamine will significantly reduce the proportion of individuals with HDDs. An important secondary hypothesis is that those receiving ketamine and behavioral treatment will demonstrate significantly better outcomes than individuals receiving ketamine alone. Other aims pertain to the effects of ketamine on number of daily drinks, and number of drinking days; the impact of ketamine on time to first HDD or drop-out; and the evaluation of added effectiveness when ketamine is combined with MET/MBRP. If successful, this project stands to contribute significantly to the treatment of AUD, for which new pharmacotherapy strategies are needed. Future studies might test other medications using the design introduced here, as well as focus on clarifying the mechanisms by which ketamine addresses AUD. !