N-acetylcysteine as a Potential Treatment for Methamphetamine Dependence

N-乙酰半胱氨酸作为甲基苯丙胺依赖的潜在治疗方法

• 批准号: 7647519
• 负责人: Thomas Frederick Newton
• 金额: $ 22.99万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7647519
• 关键词: Acetylcysteine; Animal Model; Antioxidants; Autoreceptors; Behavior; Clinical Research; Cocaine; Cues; Cysteine; Dependence; Development; Disease; Dose; Double-Blind Method; Exposure to; Extinction (Psychology); Glutamates; Hour; Human; Human Volunteers; Measures; Methamphetamine; Participant; Pharmaceutical Preparations; Placebo Control; Placebos; Predisposition; Procedures; Psychostimulant dependence; Public Health; Randomized; Rattus; Reporting; Rodent; Saline; Sampling; Self Administration; Series; System; Visual; analog; craving; design; discontinuation trial; extracellular; neurotoxic; neurotransmission; public health relevance; research study; therapeutic evaluation; treatment duration; treatment effect; virtual reality; volunteer

DESCRIPTION (provided by applicant): N-acetyl-l-cysteine (NAC) treatment is associated with reduced susceptibility to reinstatement of cocaine- seeking behavior in rats (Baker et al 2002) and with reduced cue-induced craving in cocaine-dependent human volunteers (LaRowe et al 2006). We propose these aims to evaluate the potential of NAC as a treatment for methamphetamine (MA) dependence: Specific Aim 1: To determine the effects of treatment with NAC (placebo, 1800 and 3600mg daily), compared to treatment with placebo, on cue- and MA-induced craving and MA subjective effects in non-treatment-seeking MA-dependent human volunteers. We hypothesize that treatment with NAC will reduce craving for MA reported following exposure to MA cues and will reduce craving and MA subjective effects reported following non-contingent administration of MA (0mg, 9mg, and 30 mg, IV). Specific Aim 2: To determine the effects of treatment with NAC (placebo, 1800 and 3600mg daily), compared to treatment with placebo, on the reinforcing effects of MA by measuring MA self-administration in non-treatment-seeking MA-dependent human volunteers. We hypothesize that treatment with NAC will reduce the number of choices made for MA during choice sessions. Fifteen participants will complete procedures during treatment with placebo, NAC 1800mg, and NAC 3600mg, using a within-subjects, double-blind, placebo-controlled design with at least 2 weeks separating each treatment episode. After 2 days of treatment with study medication, cue-induced craving will be assessed using visual analogue rating scales prior to and after exposing participants to MA and neutral cues using our newly developed virtual reality (VR) apparatus. Participants will then complete 2 sample sessions and 2 choice sessions, each occurring on a separate day. In sample sessions they will receive placebo, 9mg MA, and 30mg MA and subjective effects ratings will be collected. In 2 subsequent choice sessions participants will make a series of 10 choices between money and the drug available (placebo or MA) in that session. Any alterations in the reinforcing effects of MA associated with NAC treatment will be evident as changes in the number of choices made for MA. After discontinuation of study medication participants will be discharged, to return after at least 2 weeks until procedures have been completed during treatment with each dose of study medication. PUBLIC HEALTH RELEVANCE: N-acetyl-l-cysteine (NAC) treatment is associated with reduced susceptibility to reinstatement of cocaine-seeking behavior in rats and with reduced cue-induced craving in cocaine-dependent human volunteers. Therefore, we propose an exploratory/developmental clinical research study to evaluate the potential of NAC as a potential treatment in MA-dependent volunteers. This proposal is of considerable public health significance as it provides an initial evaluation of the therapeutic potential of a promising compound for the treatment of MA dependence, a disorder for which there no effective medication treatments currently exists.

描述（由申请人提供）：N-乙酰基L-半生育（NAC）治疗与大鼠恢复可卡因寻求行为的易感性降低有关（Baker等，2002），并且与可卡因依赖性人类志愿者的提示诱导的渴望降低了（Larowe等人（Larowe等人2006））。我们提出了这些旨在评估NAC作为甲基苯丙胺（MA）依赖性治疗的潜力：具体目的1：确定NAC治疗的影响（安慰剂，每天1800毫克和3600毫克），与安慰剂治疗，对提示和MA诱导的和MA诱导的迫切和MA的主体效应相比，在非企业中探索Maeking-Maeking-Ma-Ma依赖性人类依赖人Vorun everuntent。我们假设使用NAC治疗将减少报告接触MA提示后MA的渴望，并且在非固定施用MA（0mg，9mg和30 mg，IV）后，将减少渴望和MA主观效应。具体目的2：与安慰剂治疗相比，用NAC（安慰剂，1800毫克和3600毫克）治疗对MA的增强作用，通过测量MA自我给予非治疗的MA依赖人类志愿者的增强作用。我们假设使用NAC治疗将减少选择课程中对MA的选择数量。 15名参与者将在安慰剂，NAC 1800mg和NAC 3600mg的治疗过程中完成程序，并使用受试者内部，双盲，安慰剂对照设计，至少2周将每个治疗片段分开。在用研究药物治疗2天后，将使用我们新开发的虚拟现实（VR）设备在将参与者暴露于MA和中性线索之前和之后，使用视觉模拟评级量表来评估提示引起的渴望。然后，参与者将完成2次样本会议和2个选择会议，每个会议发生在一个不同的一天。在样本会话中，他们将收到安慰剂，9mg MA和30mg MA，并收集主观效果评级。在随后的两个选择会议中，参与者将在该会议中在金钱和可用药物（安慰剂或MA）之间做出一系列10个选择。随着对MA选择的选择数量的变化，MA与NAC治疗相关的增强作用的任何变化都将显而易见。在停用研究药物的参与者将在至少2周后返回，直到每种剂量的研究药物在治疗过程中都返回。公共卫生相关性：N-乙酰L-半胱氨酸（NAC）治疗与恢复大鼠可卡因寻求可卡因行为的敏感性以及可卡因依赖性人类志愿者的渴望减少有关。因此，我们提出了一项探索/发育临床研究，以评估NAC作为MA依赖志愿者的潜在治疗的潜力。该提案具有相当大的公共卫生意义，因为它提供了对MA依赖性治疗的有希望化合物的治疗潜力的初步评估，该疾病目前尚无有效的药物治疗。