DEVELOPMENT OF METHODS FOR SCREENING PHARMACOLOGIC TREATMENTS OF SUBSTANCE ABUSE

药物滥用药物治疗筛查方法的开发

• 批准号: 5201690
• 负责人: K L PRESTON
• 金额: --
• 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/5201690
• 关键词: behavior modification; behavioral habituation /sensitization; cardiovascular function; cocaine; dosage; drug abuse chemotherapy; drug addiction; emotions; human subject; human therapy evaluation; opiate alkaloid; oral administration; performance; psychopharmacology; substance abuse related disorder

We have begun a program of research to develop a laboratory model of cocaine abuse using very low doses of oral cocaine, doses that produce measurable behavioral effects but minimal cardiovascular effects. The first protocol in this research program used a drug discrimination procedure to explore the limits of human behavioral sensitivity to oral cocaine. Initially, subjects in this protocol are taught to distinguish 50 mg of oral cocaine from placebo using a drug discrimination procedure. Then subjects were exposed to 4 doses of oral cocaine (6.25 mg, 12.5 mg, 25 mg, and 50 mg) and placebo in random order across days to determine the lowest doses of cocaine that subjects can detect. A second study was initiated to identify the lowest dose of oral cocaine that subjects could detect by first teaching subjects to distinguish 50 mg of oral cocaine from placebo and then gradually decreasing the dose of oral cocaine while continuing discrimination training. Throughout both studies the cardiovascular and self-reported mood effects of these cocaine doses were determined. These studies demonstrated behavioral activity of doses of oral cocaine that are lower than those previously shown to affect human behavior. Oral cocaine produced a similar profile of self-reported mood and performance effects as cocaine administered by other routes. These methods revealed important behavioral effects of oral cocaine at doses that produced minimal or no detectable cardiovascular effects. The results of this study suggest that these procedures may be useful in studying the behavioral pharmacology of cocaine under conditions that minimize risk to subjects. Further studies are planned to study cocaine and opioid drug discrimination, cocaine and opioid self-administration studies, and a multiple-choice behavioral paradigm for screen medications.

我们已经开始了一项研究计划，开发一个实验室模型 可卡因滥用使用非常低剂量的口服可卡因，剂量产生 可测量的行为影响，但对心血管的影响最小。 这 该研究计划的第一个方案使用了药物歧视 探索人类行为对口腔的敏感性极限的程序 可卡因。 最初，该协议中的受试者被教导区分 使用药物歧视程序从安慰剂中口服 50 毫克可卡因。 然后受试者接受 4 剂口服可卡因（6.25 毫克、12.5 毫克、 25 毫克和 50 毫克）和安慰剂在几天内随机排列以确定 受试者可以检测到的可卡因的最低剂量。 第二项研究是 旨在确定受试者可以口服可卡因的最低剂量 首先教学受试者检测以区分 50 毫克口服可卡因 从安慰剂开始，然后逐渐减少口服可卡因的剂量，同时 持续进行歧视培训。 在这两项研究中 这些可卡因剂量对心血管和自我报告的情绪影响 决定。 这些研究证明了一定剂量的行为活动 口服可卡因含量低于先前显示的对人类的影响 行为。 口服可卡因产生了类似的自我报告情绪 以及通过其他途径施用可卡因时的表现效果。 这些 方法揭示了口服可卡因剂量的重要行为影响 产生最小或没有可检测到的心血管影响。 这 这项研究的结果表明，这些程序可能有助于 研究可卡因在以下条件下的行为药理学 最大限度地减少受试者的风险。 计划进一步研究可卡因 和阿片类药物歧视、可卡因和阿片类药物自我给药 研究和屏幕多项选择行为范式 药物。