Human Laboratory Model of Cocaine Treatment: Behavioral Economic Analysis

可卡因治疗的人体实验室模型：行为经济学分析

• 批准号: 7894996
• 负责人: Mark K Greenwald
• 金额: $ 69.75万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7894996
• 关键词: Accounting; Affect; Agonist; Behavior Therapy; Behavioral; Carrots - dietary; Clinical Trials; Cocaine; Cocaine Dependence; Dextroamphetamine; Disease; Dose; Drug usage; Economics; Elasticity; Frequencies; Goals; Human; Individual Differences; Inpatients; Laboratories; Magic; Modeling; Oral; Outpatients; Patients; Pharmaceutical Preparations; Pharmacotherapy; Placebos; Positive Reinforcements; Predisposition; Price; Prize; Probability; Psychological reinforcement; Public Health; Punishment; Recording of previous events; Relative (related person); Schedule; Screening procedure; Severities; Testing; Treatment Efficacy; Withdrawal Symptom; adverse outcome; analog; base; cocaine use; contingency management; cost; drug reinforcement; improved; non-drug; public health relevance; social

DESCRIPTION (provided by applicant): Background: No anti-cocaine medication will be universally effective because non-medication factors such as environmental conditions (e.g. alternatives to drug use) and individual differences (e.g. behavioral history) constrain the efficacy of any medication. Therefore, tests of cocaine medications need to be conducted in synchrony with behavior therapies also taking into account individual differences in order to understand the mechanisms of interaction and potential boundary conditions of a medication's efficacy. Approach: In this human laboratory model of cocaine treatment, we will investigate the ability of continuous and intermittent schedules of non-drug positive reinforcement ("Carrots"; analogues of standard and prize-based contingency management [CM] treatment) and punishment ("Sticks"; analogue of the adverse consequences of cocaine use) and a promising agonist-like medication for treatment of cocaine dependence (sustained release d- amphetamine [SR-AMP]) to alter cocaine demand using behavioral economic analyses. We will also prospectively explore two individual difference factors, level of cocaine use and severity of cocaine withdrawal symptoms, which may influence sensitivity to these effects. By conducting thematically integrated and parametrically organized studies (including systematic replications and extensions), we hope to understand how these factors interact (short term goal) and ultimately improve treatment efficacy for cocaine dependence (long term goal). Primary Aims: (1) Determine in a laboratory model of CM, using money as a non-drug alternative, whether: (a) higher- vs. lower-magnitude continuous positive reinforcement increases cocaine elasticity; (b) intermittent positive reinforcement conditions (which will be equated in magnitude with continuous reinforcement) differentially affect cocaine elasticity; and (c) cocaine demand is functionally equivalent at matched unit prices comprised of differing fixed ratio/unit dose combinations, (2) Determine whether (a) drug choice-contingent money loss (predictable punishment, relative to no punishment) increases cocaine elasticity, (b) higher vs. lower probabilities of punishment (equated for average magnitude of money loss) increase cocaine elasticity, and (c) the combination of higher (relative to lower) magnitude positive reinforcement and higher (relative to lower) probability of punishment additively increases cocaine elasticity. (3) Determine whether SR-AMP 15 mg BID (30 mg/day total) relative to placebo: (a) increases cocaine elasticity under minimally assisted conditions (i.e. low-magnitude non-drug reinforcement and absence of punishment), and (b) enhances the ability of positive reinforcement/punishment combinations to increase cocaine elasticity. Secondary Aim: Determine whether pre-experimental individual differences in cocaine use or withdrawal symptoms moderate the efficacy of positive reinforcement or punishment contingencies on cocaine demand. PUBLIC HEALTH RELEVANCE: As we develop medications for cocaine dependence, it is critical to investigate the extent to which non-drug (environmental and individual difference) factors influence medication efficacy. In this human laboratory model of cocaine treatment, we will programmatically examine the ability of continuous and intermittent schedules of non-drug positive reinforcement (money choice-contingent earnings) and punishment (drug choice-contingent money loss), in combination with oral sustained release d-amphetamine (vs. placebo), for reducing cocaine demand using behavioral economic analyses. We will also explore whether individual differences in cocaine use and withdrawal symptom severity influence sensitivity to these effects. Three thematically integrated and parametrically organized studies (including systematic replications and extensions) are intended to understand how these factors interact (short term goal) and to improve treatment efficacy for cocaine dependence (long term goal).

描述（由申请人提供）： 背景：没有一种抗可卡因药物会普遍有效，因为环境条件（例如药物使用的替代方案）和个体差异（例如行为史）等非药物因素限制了任何药物的功效。因此，可卡因药物的测试需要与行为疗法同步进行，同时考虑个体差异，以了解相互作用的机制和药物功效的潜在边界条件。方法：在可卡因治疗的人类实验室模型中，我们将研究连续和间歇性非药物正强化（“胡萝卜”；标准和基于奖励的应急管理[CM]治疗的类似物）和惩罚（“棍子”；可卡因使用的不良后果的类似物）和用于治疗可卡因依赖的激动剂类药物（持续释放d-）的能力。 安非他明 [SR-AMP]）使用行为经济分析来改变可卡因需求。我们还将前瞻性地探讨两个个体差异因素，即可卡因使用水平和可卡因戒断症状的严重程度，这可能会影响对这些效应的敏感性。通过进行主题整合和参数组织的研究（包括系统复制和扩展），我们希望了解这些因素如何相互作用（短期目标）并最终提高可卡因依赖的治疗效果（长期目标）。主要目标：(1) 在 CM 实验室模型中，使用金钱作为非药物替代品，确定是否： (a) 较高与较低幅度的连续正强化是否会增加可卡因弹性； (b) 间歇性正强化条件（其强度与连续强化相当）对可卡因弹性的影响不同； (c) 可卡因需求在由不同的固定比例/单位剂量组合组成的匹配单价下在功能上是等价的，(2) 确定 (a) 药物选择-或有金钱损失（可预测的惩罚，相对于无惩罚）是否会增加可卡因弹性，(b) 较高与较低的惩罚概率（相当于金钱损失的平均程度）是否会增加可卡因弹性，以及 (c) 较高的组合 （相对于较低）幅度的正强化和较高（相对于较低）的惩罚概率会增加可卡因的弹性。 (3) 确定 SR-AMP 15 mg BID（总计 30 mg/天）相对于安慰剂是否：（a）在最低限度辅助条件下（即低强度非药物强化和无惩罚）增加可卡因弹性，以及（b）增强积极强化/惩罚组合增加可卡因弹性的能力。次要目标：确定可卡因使用或戒断症状的实验前个体差异是否会调节积极强化或惩罚意外事件对可卡因需求的功效。 公共卫生相关性：当我们开发治疗可卡因依赖的药物时，研究非药物（环境和个体差异）因素影响药物疗效的程度至关重要。在这个可卡因治疗的人体实验室模型中，我们将通过行为经济学分析，有计划地检查连续和间歇性非药物正强化（金钱选择-或有收入）和惩罚（药物选择-或有金钱损失）计划，结合口服缓释d-安非他明（与安慰剂），以减少可卡因需求的能力。我们还将探讨可卡因使用和戒断症状严重程度的个体差异是否会影响对这些效应的敏感性。三项主题整合和参数组织的研究（包括系统复制和扩展）旨在了解这些因素如何相互作用（短期目标）并提高可卡因依赖的治疗效果（长期目标）。

项目成果

N-acetylcysteine reduces cocaine-seeking behavior and anterior cingulate glutamate/glutamine levels among cocaine-dependent individuals.

• DOI: 10.1111/adb.12900
• 发表时间: 2021-03
• 期刊: ADDICTION BIOLOGY
• 影响因子: 3.4
• 作者: Woodcock, Eric A.;Lundahl, Leslie H.;Khatib, Dalal;Stanley, Jeffrey A.;Greenwald, Mark K.
• 通讯作者: Greenwald, Mark K.