Effects of Opioid Pharmacotherapy on Functioning

描述（由申请人提供）：阿片类药物依赖是一个重大的公共卫生问题，最广泛的单一干预措施是药物治疗（例如美沙酮维持）。药物治疗的一个重要好处是，它可以提供必要的稳定性，以启动生活方式的改变，获得稳定的就业和社会功能。因此，一个关键的问题是药物治疗在多大程度上与可能影响功能的精神运动和认知表现的损害有关。然而，很少有控制良好的研究使用复杂的评估技术来解决这个问题。在这项具有翻译意义的研究应用中，提出了四个实验来评估药物治疗阿片类药物依赖对与日常活动表现相关的广泛功能的影响，以及参与和受益于药物滥用治疗的认知/社会心理方面，包括动眼肌功能、感觉知觉、精神运动协调、反应时间、视觉跟踪、注意力（集中、选择性和分裂）。概念灵活性，工作记忆，情景记忆和元记忆/元认知，使用最先进的评估技术和复杂的药理学操作。具体目标1是比较美沙酮和新批准的丁丙诺啡/纳洛酮联合产品对性能的慢性影响，并将在实验1中使用实验性剂量设计对阿片类药物依赖滥用者进行测试。具体目标2是评估高剂量美沙酮对性能的慢性影响，并将在实验1中使用实验剂量设计进行测试，在实验2中使用患者组比较设计来比较当地诊所已有的三组美沙酮维持患者的性能，包括维持高于先前在对照研究中评估的剂量的组。具体目标3-4是评估美沙酮对表现的急性影响以及美沙酮与酒精（阿片类药物滥用者常滥用的一种药物）联合使用对表现的影响，并将在实验3-4中的急性剂量设计中对依赖和非依赖阿片类药物滥用者进行测试。具体目标5是评估美沙酮引起的功能障碍的程度，相对于有充分证据证明对功能有影响的药物引起的功能障碍，并将在实验4中以酒精作为参考进行测试。从这个项目中获得的信息可以被临床医生用来指导重要的决策，如药物选择和给药计划，教育患者预期的效果和相互作用，以及潜在的活动限制，并根据正在接受药物治疗的阿片类药物滥用者的特定认知能力量身定制非药物治疗干预措施。这个项目的数据也可以增强对药理学和认知机制的科学理解。

DESCRIPTION (provided by applicant): Opioid dependence is a significant public health problem and the most widespread single intervention is pharmacological treatment (e.g., methadone maintenance). An important benefit of pharmacotherapy is that it can provide the stability necessary to initiate lifestyle changes, obtain steady employment and function in society. Thus, a critical question is the extent to which pharmacotherapy is associated with impairment in psychomotor and cognitive performance that might affect functioning. Yet, few well-controlled studies using sophisticated assessment techniques have addressed this question. In this research application with translational implications, four experiments are proposed to evaluate the effects of pharmacotherapy for opioid dependence on a wide range of functions relevant to performance of daily activities and to participating in and benefiting from cognitive/psychosocial aspects of substance abuse treatment, including oculomotor function, sensory perception, psychomotor coordination, reaction time, visual tracking, attention (focused, selective, and divided), conceptual flexibility, working memory, episodic memory, and metamemory/metacognition, using state-of-the-art assessment techniques and sophisticated pharmacological manipulations. Specific Aim 1 is to compare the chronic effects on performance of methadone and the newly-approved buprenorphine/naloxone combination product, and will be tested in Experiment 1 using an experimental dosing design in dependent opioid abusers. Specific Aim 2 is to evaluate the chronic effects of high-dose methadone on performance, and will be tested in Experiment 1 using an experimental dosing design and in Experiment 2 using a patient group comparison design to compare the performance of three pre-existing groups of methadone maintenance patients in local clinics, including a group maintained on higher doses than those previously evaluated in controlled studies. Specific Aims 3-4 are to evaluate the acute effects of methadone on performance and the effects on performance of methadone in combination with alcohol (a drug commonly abused by opioid abusers), and will be tested in an acute dosing design in Experiments 3-4 in dependent and non-dependent opioid abusers. Specific Aim 5 is to evaluate the magnitude of methadone-induced performance impairment relative to that induced by a drug with well-documented effects on functioning, and will be tested in Experiment 4 using alcohol as a reference. Information obtained from this project can be used by clinicians to guide important decisions such as medication selection and dosing schedules, to educate patients about expected effects and interactions, as well as potential activity restrictions, and to tailor non-pharmacological treatment interventions to the specific cognitive capabilities of opioid abusers being treated with pharmacotherapy. Data from this project may also enhance the scientific understanding of pharmacological and cognitive mechanisms.