Development of a Family-Based Treatment for Adolescent Methamphetamine Abuse

描述（由申请人提供）：甲基苯丙胺（冰毒）滥用在美国已达到流行病的比例，特别是在西部各州，并已与一系列身体和心理问题。更令人不安的是，在青少年时期使用冰毒可能会干扰正常的大脑发育。这些研究结果表明，冰毒的地方性使用将需要针对青少年滥用者开发和测试有效的治疗方法，以防止潜在的有害结果。此外，在跨学科模式中结合临床和神经科学方法应该会导致更规范和有效的治疗。因此，在目前的研究中，我们将冰毒特异性干预措施的发展与冰毒使用如何影响神经系统以及特定大脑区域的改变如何影响治疗反应的更详细检查相结合。拟议的研究代表了IA/IB阶段的治疗开发项目，利用跨学科的方法，与NIH路线图一致，旨在开发，完善和试点测试青少年冰毒滥用或依赖的理论基础干预。甲基特异性干预（AMT）将整合家庭治疗与有效的成人甲基治疗计划的核心要素，适应青少年的发展。这将与独立的家庭治疗干预（FFT）进行比较，FFT是一种有效的青少年物质使用障碍治疗方法。此外，为了告知我们的治疗方法，将开发一项实验室任务来测量决策（即，冒险和冲动），并结合功能性脑成像程序（fMRI）来评估冰毒和其他药物使用对这些认知功能背后的神经回路的影响。我们的1A阶段研究目标是开发和测试甲基特异性手动治疗方案。同样，我们将检查我们的功能磁共振成像程序的有效性，在评估已知受冰毒影响的大脑中与奖励相关的通路的功能，在一个由32名接受冰毒治疗的青少年和16名非吸毒对照组成的子集中，以确定两组决策相关的大脑结构是否有显著差异。第1B阶段的目标是对手动AMT程序进行初步测试，以确定其可行性并验证其与FFT的区分度，通过检查参与率和保留率来验证治疗的可接受性，确定相对于单独FFT的显著临床结局，并检查预测的介导因子和调节因子，以确定治疗疗效的核心机制。fMRI测量将被视为相对于通知治疗参与和保留以及短期和长期治疗结果。第1B阶段的研究将涉及60名青少年冰毒滥用者，他们被随机分配到AMT或FFT组，他们将在治疗前、治疗开始后3个月和6个月进行评估。该研究的最终目的是评估AMT干预的潜在前景，如fMRI技术所示，以在正式的第2阶段临床试验中进行进一步研究。

DESCRIPTION (provided by applicant): Methamphetamine (meth) abuse in the U.S. has reached epidemic proportions, especially in the Western States and has been linked to a host of physical and psychological problems. Even more troubling, meth use during the adolescent period may interfere with normal brain development. These findings suggest that the endemic use of meth will require the development and testing of effective treatments aimed at adolescent abusers to forestall potentially deleterious outcomes. Moreover, combining clinical and neuroscientific approaches in an interdisciplinary model should lead to more prescriptive and efficacious treatments. In the current study, therefore, we merge the development of meth-specific interventions with a more detailed examination of how meth use affects neural systems and how alterations in specific brain areas influence treatment response. The proposed study represents a Stage IA/IB treatment development project, utilizing an interdisciplinary approach, consistent with the NIH Roadmap and designed to develop, refine, and pilot test a theoretically grounded intervention for adolescent meth abuse or dependence. The meth-specific intervention (AMT) will integrate family therapy with core elements of effective adult meth treatment programs, adapted to be developmentally appropriate for adolescents. This will be compared to a stand-alone family therapy intervention (FFT), an efficacious and effective treatment for adolescent substance use disorders. Further, in an effort to inform our treatment approach, a laboratory task will be developed to measure decision-making (i.e., risk-taking and impulsivity) and combined with functional brain imaging procedures (fMRI) to assess the effect of meth and other drug use on the neural circuits underlying these cognitive functions. Our Stage 1A research aim is to develop and test the meth-specific manualized treatment protocol. As well, we will examine the validity of our fMRI procedures in assessing the function of reward-related pathways in the brain known to be affected by meth in a subset of 32 adolescents referred for meth treatment and 16 nondrug-using controls to determine if the brain structures underlying decision-making in the two groups differ significantly. Stage 1B aims following will pilot test the manualized AMT procedure to establish its feasibility and validate its discriminability from FFT, verify the acceptability of the treatment by examining rates of engagement and retention, determine significant clinical outcomes relative to FFT alone, and examine predicted mediators and moderators to determine the core mechanisms of treatment efficacy. fMRI measures will be viewed relative to informing treatment engagement and retention as well as both short-term and long-term treatment outcomes. Stage 1B research will involve 60 adolescent meth abusers randomly assigned to either AMT or FFT who will be assessed at pretreatment, and at 3- months and 6-months following treatment initiation. The ultimate purpose of the research is to evaluate the potential promise of the AMT intervention, as informed by fMRI technology, for further investigation in a formal Stage 2 clinical trial.