Immunopharmacotherapy for Methamphetamine Addiction

描述（由申请人提供）：d-甲基苯丙胺（冰毒）的滥用和成瘾会干扰个人健康、职业表现、人际关系和财务状况的许多方面。冰毒滥用和冰毒交易的行为后果也使美国的法律和紧急医疗资源紧张。因此，冰毒是一个重大和持续的公共卫生问题。目前治疗冰毒成瘾的方法不是完全有效的，也没有批准的药物治疗冰毒成瘾的存在。最近使用免疫治疗方法治疗可卡因和尼古丁成瘾的早期临床试验取得了成功，这激发了人们对开发治疗甲基苯丙胺成瘾的类似方法的兴趣。在该项目的初始资助期下，研究人员已经研制出MH6疫苗，该疫苗被证明能产生抗体，将甲基安非他明隔离在血液中。疫苗还减弱了甲基苯丙胺对运动活动、体温调节和静脉注射甲基苯丙胺的影响。新的研究试图通过确定不同载体蛋白和佐剂的作用来优化疫苗以获得更高的抗体滴度。在大鼠身上的研究将使用药物相关奖励的聚合模型，包括颅内自我刺激奖励和伏隔核壳中的多巴胺反应，以确定疫苗如何改变自我给药的获得。进一步的工作将确定一种优化的疫苗是否能够通过长期获取程序防止升级为不受管制的甲基苯丙胺摄入，以及该疫苗是否能够扭转既定的自我给药模式。这些研究将在优化抗甲基苯丙胺疫苗的设计和可能的转化应用方面取得重大进展。

DESCRIPTION (provided by applicant): The abuse of, and addiction to, d-methamphetamine (METH) interferes with many aspects of personal health, vocational performance, interpersonal relationships and financial well-being. Behavioral consequences of METH abuse and the METH trade also strain legal and emergency medical resources throughout the US. METH is therefore a significant and continuing public health concern. Current therapeutic approaches for METH addiction are less than completely effective and no approved pharmacotherapies for METH addiction exist. Recent successes in early clinical trials using immunotherapeutic approaches for cocaine and nicotine addiction have motivated interest in creating similar approaches for methamphetamine addiction. Work under the initial funding interval of this project has created the MH6 vaccine which was shown to generate antibodies which sequester METH in the blood. The vaccine also attenuated METH effects on locomotor activity, thermoregulation and intravenous self-administration of METH. New studies seek to optimize the vaccine for higher antibody titer by determining effects of different carrier proteins and adjuvants. Studies in rats will use converging models of drug-related reward, including intracranial self-stimulation reward and the dopamine response in the nucleus accumbens shell, to determine how the vaccine alters the acquisition of self- administration. Additional work will determine if an optimized vaccine can prevent the escalation to unregulated METH intake using a long-access procedure and if the vaccine can reverse an established self-administration pattern. Together these studies will make significant progress on optimizing both the design and likely translational application of an anti-METH vaccine.