Development Of New Pharmacologic And Biologic Treatments For Drug Dependence

药物依赖性新药物和生物治疗的开发

• 批准号: 8148495
• 负责人: DAVID ALAN GORELICK
• 金额: $ 25.52万
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 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/8148495
• 关键词: Binding; Brain region; Counseling; Development; Drug Addiction; Drug abuse; Human immunodeficiency virus test; Marijuana Receptor; Pharmaceutical Preparations; Risk Reduction; rimonabant

This project explores pharmacodynamic approaches to developing new treatments for drug dependence and reduction of HIV transmission risk behaviors, with a current focus on cocaine, marijuana, and nicotine dependence. Many subjects are at high risk for contracting and spreading HIV infection. HIV transmission risk behaviors are assessed and HIV testing and risk reduction counseling are offered to all subjects. The pharmacokinetic approach being studied is blunting the rate of onset of drug effect by enhancement of drug metabolism. Rate of onset of drug effect is considered an important influence on the reinforcing effects of drugs. The influence of rate has treatment implications, in that drugs from the same pharmacologic class but with slower rate of onset may have therapeutic efficacy without themselves inducing addiction. Pharmacodynamic approaches being studied include modulation of brain neurotransmitters and blockade of relevant neurotransmitter receptors. The former approach is being implemented using transcranial magnetic stimulation (TMS), in collaboration with the Maryland Psychiatric Research Center. TMS involves projecting pulsed magnetic fields through the skull into the brain, where they alter neuronal firing and change levels of neurotransmitters. TMS is a safe, non-invasive way of modulating activity in brain circuits that mediate drug craving and reward, thus offering a potential treatment for drug addiction. Pilot studies are being conducted to evaluate the safety and efficacy of either single-pulse or low-frequency repetitive TMS in users of cannabis, cocaine, and nicotine. A pilot study showed that functional magnetic resonance imaging (fMRI) could be successfully used to target TMS pulses to a desired brain region. The second approach is being implemented, in collaboration with the Chemistry & Drug Metabolism Section and the Maryland Psychiatric Research Center, by evaluating the effects in humans of an experimental compound, rimonabant, which acts as an antagonist at the cannabinoid 1 (CB1, marijuana) receptor in the brain. Previous studies found that rimonabant blocked the effects of smoked marijuana, without altering THC plasma pharmacokinetics, suggesting that CB1 receptors play an important role in mediating the effects of marijuana in humans. Recently terminated studies evaluated the interaction of rimonabant with oral THC and its safety and efficacy in patients with schizophrenia.

该项目探讨了为开发用于药物依赖和减少HIV传播风险行为的新治疗方法的药效方法，目前关注可卡因，大麻和尼古丁依赖性。许多受试者有收缩和传播艾滋病毒感染的高风险。评估HIV传播风险行为，并向所有受试者提供艾滋病毒测试和降低风险咨询。所研究的药代动力学方法是通过增强药物代谢来使药物作用发作率降低。药物作用的发作率被认为是对药物增强作用的重要影响。率的影响具有治疗意义，因为来自同一药物类别但发病率较慢的药物可能具有治疗功效而不会诱发成瘾。 研究的药效方法包括调节脑神经递质和相关神经递质受体的阻断。 前者与马里兰州精神病研究中心合作，使用经颅磁刺激（TMS）实施了这种方法。 TMS涉及通过头骨将脉冲磁场投射到大脑中，它们会改变神经元的发射并改变神经递质的水平。 TMS是一种调节介导药物渴望和奖励的脑回路活动的安全，无创的方法，从而为药物成瘾提供了潜在的治疗方法。 正在进行试点研究，以评估大麻，可卡因和尼古丁用户中单脉冲或低频重复TMS的安全性和功效。 一项初步研究表明，功能磁共振成像（fMRI）可以成功地将TMS脉冲靶向所需的大脑区域。 第二种方法正在与化学和药物代谢部分和马里兰州精神病学研究中心合作，通过评估人类对大脑中大麻素1（CB1，大麻）受体的拮抗剂的影响，通过评估人类的影响。 先前的研究发现，Rimonabant阻止了烟熏大麻的作用，而不会改变THC血浆药代动力学，这表明CB1受体在介导大麻对人类的影响中起着重要作用。最近终止的研究评估了Rimonabant与口服THC的相互作用及其在精神分裂症患者中的安全性和功效。