RIVASTIGMINE AS A TREATMENT FOR METHAMPHETAMINE DEPENDENCE

卡巴拉汀治疗甲基苯丙胺依赖

• 批准号: 8356773
• 负责人: Richard De La Garza
• 金额: $ 3.4万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8356773
• 关键词: Acetylcholinesterase Inhibitors; Admission activity; Alzheimer' s Disease; Attenuated; Behavior; Clinical; Clinical Research; Dose; Double-Blind Method; Evaluation; Exhibits; Exposure to; Funding; Grant; Human; Laboratories; Laboratory Study; Measures; Methamphetamine; Methamphetamine dependence; National Center for Research Resources; Nicotinic Receptors; Participant; Placebo Control; Principal Investigator; Psychological reinforcement; Rattus; Reporting; Research; Research Infrastructure; Resources; Screening procedure; Self Administration; Source; United States National Institutes of Health; Work; base; cost; craving; donepezil; dosage; pre-clinical; rivastigmine

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT We recently completed a double-blind placebo-controlled human laboratory study demonstrating that treatment with a low dose of the acetylcholinesterase (AChE) inhibitor rivastigmine reduced methamphetamine (MA)-induced craving (see Preliminary Studies, Fig. 2). This finding is consistent with the preclinical report indicating that the AChE inhibitor donepezil reduced MA-seeking behavior in rats following exposure to a non-contingent dose of MA (Hiranita et al. 2006). To extend our clinical findings, we propose a 3-year human laboratory study to evaluate effects of higher doses of rivastigmine on MA-induced craving and on self-administration of MA. Our recently completed work indicates that 3mg rivastigmine attenuated MA-induced craving in the laboratory. Given that higher dosages of this produce greater inhibition of nicotinic acetylcholine (ACh) receptors (in the treatment of Alzheimers disease), it is reasonable to predict that 6mg and 12mg will have more pronounced effects on craving and other measures of reinforcement. This human laboratory study is a critical next step in the evaluation of rivastigmine as a potential treatment for MA dependence. We propose to include only participants exhibiting MA-induced craving by screening potential participants prior to admission (criterion based upon Preliminary Studies, Fig. 5). Selection of participants demonstrating MA-induced craving will facilitate assessment of effects of rivastigmine on craving.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 抽象的 我们最近完成了一项双盲安慰剂对照人体实验室研究，证明低剂量乙酰胆碱酯酶 (AChE) 抑制剂卡巴拉汀治疗可减少甲基苯丙胺 (MA) 诱发的渴望（参见初步研究，图 2）。这一发现与临床前报告一致，表明乙酰胆碱酯酶抑制剂多奈哌齐可减少暴露于非偶然剂量的 MA 后大鼠的 MA 寻求行为（Hiranita 等，2006）。为了扩展我们的临床发现，我们提出了一项为期 3 年的人体实验室研究，以评估高剂量卡巴拉汀对 MA 诱发的渴望和自我服用 MA 的影响。 我们最近完成的研究表明，3 毫克卡巴拉汀在实验室中减弱了 MA 引起的渴望。鉴于较高剂量的这种药物会对烟碱乙酰胆碱 (ACh) 受体产生更大的抑制（在阿尔茨海默病的治疗中），因此可以合理地预测 6 毫克和 12 毫克将对渴望和其他强化措施产生更明显的影响。这项人体实验室研究是评估卡巴拉汀作为 MA 依赖性潜在治疗方法的关键下一步。 我们建议通过在入院前筛选潜在参与者（基于初步研究的标准，图 5），仅纳入表现出 MA 引起的渴望的参与者。选择表现出 MA 引起的渴望的参与者将有助于评估卡巴拉汀对渴望的影响。