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）滥用在美国已经达到流行病的程度，特别是在西部各州，并且与许多身体和心理问题有关。更麻烦的是，青少年时期使用冰毒可能会干扰正常的大脑发育。这些发现表明，冰毒的地方性使用需要开发和测试针对青少年滥用者的有效治疗方法，以预防潜在的有害后果。此外，结合临床和神经科学的方法在一个跨学科的模式应该导致更规范和有效的治疗。因此，在目前的研究中，我们将甲基苯丙胺特异性干预措施的发展与甲基苯丙胺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结合起来。拟议的研究代表了IA/IB阶段治疗开发项目，利用跨学科方法，与NIH路线图一致，旨在开发、完善和试点测试一种理论上基于青少年冰毒滥用或依赖的干预措施。冰毒特异性干预（AMT）将把家庭治疗与有效的成人冰毒治疗方案的核心要素结合起来，使其适应青少年的发展。这将与独立的家庭治疗干预（FFT）进行比较，FFT是对青少年物质使用障碍的有效治疗。此外，为了给我们的治疗方法提供信息，我们将开发一个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1A阶段的研究目标是开发和测试特定于冰毒的手动治疗方案。同时，我们将检验fMRI程序的有效性，以评估32名接受冰毒治疗的青少年和16名不使用毒品的对照组中已知受冰毒影响的大脑中奖励相关通路的功能，以确定两组中潜在决策的大脑结构是否有显著差异。1B阶段的目标是对人工AMT程序进行试点测试，以确定其可行性并验证其与FFT的区别性，通过检查参与和保留率来验证治疗的可接受性，确定相对于单独FFT的显著临床结果，并检查预测的中介和调节因子，以确定治疗效果的核心机制。功能磁共振成像测量将相对于告知治疗参与和保留以及短期和长期治疗结果。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中，他们将在治疗前、治疗开始后3个月和6个月进行评估。这项研究的最终目的是评估AMT干预的潜在前景，根据fMRI技术的信息，在正式的2期临床试验中进行进一步的研究。

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.