Project 3 - Prevention of Cocaine Abuse with Electrical Acupuncture

项目 3 - 通过电针预防可卡因滥用

• 批准号: 7667982
• 负责人: JI-SHENG HAN
• 金额: $ 29.37万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7667982
• 关键词: Acupuncture Analgesia; Acupuncture Points; Acupuncture procedure; Adverse effects; Alcohols; Alternative Therapies; Amygdaloid structure; Animal Experiments; Animals; Area; Brain; Brain imaging; Chemicals; Chinese People; Clinical; Cocaine; Cocaine Abuse; Cocaine Dependence; Condition; Control Groups; Dependence; Devices; Disease; Dopamine; Drug abuse; Dynorphins; Ear Acupuncture; Effectiveness; Electroacupuncture; Electrodes; Electronics; Endorphins; Enkephalins; Frequencies; Functional Magnetic Resonance Imaging; Hand; Heroin; Heroin Dependence; Human; Invasive; Mediating; Mediator of activation protein; Methamphetamine; Methods; Microinjections; Molecular Mechanisms of Action; N.I.H. Research Support; Nerve; Neurobiology; Neuromodulator; Neuropeptides; Neurotransmitters; Nucleus Accumbens; Opiate Addiction; Opiates; Opioid Peptide; Outpatients; Pain; Patients; Perfusion; Pharmaceutical Preparations; Pharmacological Treatment; Physical Dependence; Population; Prevention; Principal Investigator; Randomized Controlled Clinical Trials; Rattus; Relapse; Research Project Grants; Rodent Model; Skin; Substance Abuse, Other; Substance Withdrawal Syndrome; System; Techniques; Testing; Therapeutic Effect; Time; Transcutaneous Electric Nerve Stimulation; Upper arm; Ventral Tegmental Area; Withdrawal; Work; base; craving; delta opioid receptor; drug relapse; experience; insight; interest; novel strategies; opioid abuse; preference; prevent; programs; receptor; research study

The objective of this Research Project 3 is to evaluate the effect of electrical acupuncture (EA), specifically the non-invasive HANS method of transcutaneous electric stimulation, for the prevention of drug relapse, and to provide insight into the mechanism of action. Acupuncture is a 3000-year-old Chinese therapy commonly used to treat disease and relieve pain. Recently, the scientific basis of acupuncture has been founded, at least partly, on the frequency-dependent release of opioid peptides in the CNS. For example, high frequency (100-Hz) stimulation is more effective than low frequency (2-Hz) stimulation in reducing the opiate withdrawal syndrome by activating the dynorphin system mediated by kappa opoid receptors, but low frequency is more effective than high frequency in reducing opiate craving by activating the endorphin/enkephalin system mediated by mu/delta opioid receptors. In contrast to opiate addiction, relief from cocaine addiction seems to work through a slightly different mechanism, such that the conditioned place preference (CPP) for cocaine, a rodent model of cocaine craving, can be suppressed by 100-Hz but not by 2-Hz stimulation. Based on the successful experience of the PI's (Dr. Han) previous treatment of patients for heroin withdrawal, we propose to evaluate the potential of the HANS method for the prevention of cocaine relapse, and to investigate the molecular mechanism of action. The specific aims are (1) to further explore the mechanisms of EA suppression of cocaine CPP in rats, including brain areas and chemical mediators involved, using microinjection and brain push-pull perfusion techniques, and immunohistochemical examination, with a focus on brain areas such as the ventral tegmentum, nucleus accumbens, and amygdala, and on neurotransmitters and neuromodulators such as dopamine, enkepahlin, and dynorphin; (2) to use functional magnetic resonance imaging (fMRI) in rats and humans to characterize the difference in brain between cocaine dependent and non-dependent subjects, and the difference between 2-Hz (non effective) and 100-Hz (effective) treatment groups, to verify the findings obtained in Aim 1; and (3) to conduct a randomized, controlled clinical trial to test the effectiveness of HANS in treating cocaine addiction. In the HANS group, real current is delivered to the patient, with skin electrodes applied on the body acupoint Heku (LI 4)/Laogong (P 8) on one hand and Neiguan (P 6)/Waiguan (TE 5) on the other arm. The current can be set to two times threshold (one T = 5 mA). The control group receives a modified (mock) HANS at 2Hz, which is equivalent to "minimal acupuncture". We speculate that the HANS will produce a significantly better therapeutic effect than the mock HANS in suppressing craving and preventing relapse. In summary, acupuncture by transcutaneous electrical stimulation is a highly attractive alternative therapy for the treatment of drug abuse. This approach differs from pharmacological treatment primarily in being a non-invasive, safe way to make the body release its own natural chemicals to prevent relapse.

该研究项目 3 的目的是评估电针（EA）的效果，特别是非侵入性的经皮电刺激 HANS 方法，对于预防药物复发的效果，并深入了解其作用机制。针灸是一种具有3000年历史的中医疗法，常用于治疗疾病和缓解疼痛。最近，针灸的科学基础至少部分建立在中枢神经系统中阿片肽的频率依赖性释放上。例如，高频（100赫兹）刺激比低频（2赫兹）刺激通过激活κ阿片受体介导的强啡肽系统来减少阿片戒断综合征更有效，但低频比高频更有效通过激活 mu/delta 阿片受体介导的内啡肽/脑啡肽系统来减少对阿片的渴望。与鸦片成瘾相反，可卡因的缓解 成瘾似乎通过一种稍微不同的机制起作用，例如对可卡因的条件性位置偏好（CPP）（一种啮齿动物渴望可卡因的模型）可以被 100 Hz 刺激抑制，但不能被 2 Hz 刺激抑制。基于PI（韩博士）以往治疗海洛因戒断患者的成功经验，我们建议评估HANS方法预防可卡因复吸的潜力，并探讨其分子机制。 行动。具体目的是（1）利用显微注射和脑推拉灌注技术以及免疫组化检查，进一步探讨电针抑制大鼠可卡因CPP的机制，包括所涉及的脑区和化学介质。如腹侧被盖、伏隔核和杏仁核，以及神经递质和神经调节剂，如多巴胺、脑啡肽和强啡肽； (2) 使用 对大鼠和人类进行功能磁共振成像 (fMRI)，以表征可卡因依赖和非依赖受试者之间的大脑差异，以及 2-Hz（无效）和 100-Hz（有效）治疗组之间的差异，以验证目标 1 中获得的结果； (3) 进行一项随机对照临床试验，以测试 HANS 治疗可卡因成瘾的有效性。在 HANS 组中，真实电流通过皮肤传递给患者 电极应用于一只手的体穴合库 (LI 4)/劳宫 (P 8) 和另一只手臂的内关 (P 6)/外关 (TE 5)。电流可设置为阈值的两倍（1 T = 5 mA）。对照组接受 2Hz 的改良（模拟）HANS，相当于“最小针灸”。我们推测，HANS 在抑制烟瘾和预防复发方面将比模拟 HANS 产生明显更好的治疗效果。总之，经皮电刺激针灸是治疗药物滥用的一种极具吸引力的替代疗法。这种方法与药物治疗的主要区别在于它是一种非侵入性、安全的方法，可以使身体释放自己的天然化学物质以防止复发。