Immunopharmacotherapy for Methamphetamine Addiction

D-甲基苯丙胺（METH）的滥用和成瘾干扰了许多方面的治疗。 个人健康、职业表现、人际关系和财务状况。 甲基苯丙胺滥用和甲基苯丙胺贸易的行为后果也使法律的和紧急情况变得紧张 美国各地的医疗资源。因此，METH是一个重要的和持续的公共卫生 关心目前治疗METH成瘾的方法不完全有效， 存在用于METH成瘾的批准的药物疗法。最近在早期临床试验中取得的成功， 针对可卡因和尼古丁成瘾的免疫疗法激发了人们对创造 类似的方法来治疗甲基苯丙胺成瘾。在本项目的初始资助间隔下工作 一个项目创造了MH 6疫苗，该疫苗被证明能产生隔离METH的抗体 血液中该疫苗还减弱了METH对自发活动、体温调节和 静脉内自我给药METH。新的研究寻求优化疫苗以获得更高的抗体 通过测定不同载体蛋白和佐剂的作用来测定效价。大鼠研究将使用聚合 药物相关奖赏模型，包括颅内自我刺激奖赏和多巴胺 反应的核壳，以确定如何改变疫苗的收购自我- 局额外的工作将确定优化的疫苗是否可以防止升级到 使用长期接触程序的不受管制的METH摄入量，如果疫苗可以逆转既定的 自我管理模式。总之，这些研究将在优化 抗METH疫苗的设计和可能的翻译应用。

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.