Prevention of Relapse in Addiction

预防成瘾复吸

• 批准号: 8336482
• 负责人: Kenzie Preston
• 金额: $ 129.38万
• 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/8336482
• 关键词: Adrenergic Agonists; Attenuated; Behavior; Behavioral; Boredom; Buprenorphine; Clinical; Clinical Trials; Clonidine; Cocaine; Cocaine Users; Complex; Cues; Data; Devices; Dose; Drug Exposure; Drug usage; Electronics; Environment; Experimental Models; Exposure to; Extinction (Psychology); Goals; Handheld Computers; Happiness; Heroin; Heroin Abuse; Hour; Human; Individual; Intervention; Laboratory Animals; Laboratory Study; Lead; Maintenance; Measurement; Methadone; Modeling; Moods; Natural History; Opioid; Outcome; Outpatients; Participant; Pathway interactions; Pharmaceutical Preparations; Physiological; Rattus; Relapse; Relaxation; Reporting; Role; Self Administration; Shock; Stress; Testing; Thinking; Time; Tobacco; addiction; alpha 2 agonist; cocaine use; craving; disorder later incidence prevention; drug abuser; drug of abuse; experience; foot; irritation; negative mood; pre-clinical; prevent; prospective; trend

Stress has been shown to induce resumption of drug seeking in laboratory animals. The experimental model is reinstatement of operant behavior following extinction of previously acquired drug self-administration. Physical stress in the form of electric foot-shock has been consistently shown to lead to reinstatement of heroin and cocaine seeking in rats (Shaham and Stewart, 1995; Erb et al., 1996; Shaham, 1996). This stress-induced reinstatement is blocked by the alpha-2 adrenergic receptor agonist clonidine (Erb et al., 2000; Shaham et al., 2000; Highfield et al., 2001). The alpha-2 agonists may act upon some final common pathway of stress-induced relapse, relevant to multiple drugs of abuse. We tested the effect of clonidine on stress- and cue-induced craving in human cocaine users in a laboratory study and found that responsivity to stress scripts was significantly attenuated by clonidine 0.1 and 0.2 mg; responsivity to drug-cue scripts was significantly attenuated at the higher clonidine dose (0.2 mg) only. Thus, clonidine may reduce cocaine craving and some physiological reactivity in drug abusers experiencing stressful situations or situations that remind them of drug use. To test the clinical utility of this finding, we are conducting a clinical trial of clonidine for the prevention of relapse to illicit opioid use in individuals in buprenorphine maintenance. We are using handheld electronic devices as part of our outcome measurement, so we should be able to determine whether clonidine is differentiallty effective in preventing lapses associated with stress exposure versus cue exposure. We are also evaluating the role of stress in relapse in natural-history studies in which we collect quantitative real-time data on the stress experienced by drug misusers in their daily lives. We evaluated the occurrence of stress in relation to craving, mood, relapse-trigger exposure, and cocaine use in methadone-maintained cocaine- and heroin-abusing outpatients who provided ecological momentary assessment (EMA) data on handheld computers. Ratings of stress were compared to those of craving and mood and past-hour exposure to putative drug-use triggers in randomly prompted entries, and in the 5 hours prior to participant-initiated cocaine use reports. Stress had significant positive relationships with current ratings of craving for cocaine, heroin, and tobacco and with ratings of tiredness, boredom, and irritation, and had significant negative relationships with ratings of happiness and relaxation. Stress was significantly greater in entries in which participants also reported past-hour exposure to negative-mood triggers, most of the drug-exposure triggers, or any trigger involving thoughts about drugs (e.g., tempted out of the blue). The linear increase in stress during the five hours preceding individual episodes of cocaine use was not significant, though there was a trend for such an increase before the use episodes that participants attributed to stressful states when they occurred. The findings suggest a complex role of stress in addiction. Stress reported in real time in the natural environment showed strong cross-sectional momentary relationships with craving, mood, and exposure to drug-use trigger. However, the prospective association between stress ratings and cocaine-use episodes was, at best, weak. This combination of expected and unexpected findings illustrates the value of collecting real-time, in-the-field behavioral data that can be quantified and aggregated for analysis.

已证明应力引起实验动物中寻求药物的恢复。实验模型是在先前获得的药物自我管理灭绝后恢复操作行为。始终显示出电动脚震形式的身体压力会导致在大鼠中恢复海洛因和可卡因（Shaham and Stewart，1995; Erb等，1996; Shaham，1996）。这种应力诱导的恢复原状被α-2肾上腺素能受体激动剂可乐定阻断（Erb等，2000； Shaham等，2000； Highfield等，2001）。 Alpha-2激动剂可以采取与多种滥用药物有关的压力引起的复发的最终共同途径。我们在一项实验室研究中测试了可乐定和提示引起的可卡因使用者的渴望和提示引起的渴望的影响，并发现克罗尼丁0.1和0.2 mg可大大减弱对压力脚本的响应。仅在较高的可乐定剂量（0.2 mg）下，对药物脚本的反应显着减弱。因此，可乐定可以减少可卡因的渴望，并在施加压力的情况或情况下，使他们想起吸毒的情况下的毒品施肥和某些生理反应性。 为了测试这一发现的临床实用性，我们正在对丁丙诺啡维持的个体中的非法阿片类药物的复发进行临床试验，以预防复发。我们将手持电子设备作为结果测量的一部分，因此我们应该能够确定可乐定在防止与压力暴露与提示暴露相关的失误方面是否有效。 我们还评估了压力在自然历史研究中复发中的作用，在这些研究中，我们收集了滥用药物在日常生活中遇到的压力的定量实时数据。我们评估了与美沙酮维护可卡因和滥用海洛因的门诊患者相对于渴望，情绪，复发触发的暴露以及可卡因使用的压力的发生，这些药物提供了手持计算机的生态瞬时评估（EMA）数据。将压力的评分与渴望，情绪的评分以及在随机提示的条目中以及参与者发起的可卡因使用报告之前的5个小时内对推定的药物使用触发器的持续时间进行了比较。压力与当前对可卡因，海洛因和烟草的渴望等级以及疲倦，无聊和刺激的评分具有显着的积极关系，并且与幸福和放松的评分有着显着的负面关系。参与者还报告了前几个小时暴露于负MOOD触发因素，大多数药物暴露触发因素或任何涉及对药物思想的触发因素（例如，从蓝色诱惑）的参与者中，应力明显更大。在使用可卡因的单个发作之前的五个小时内，应力的线性增加并不显着，尽管在使用发作之前有这种增加的趋势，即参与者在发生时归因于压力状态。研究结果表明，压力在成瘾中的重要作用。自然环境中实时报道的压力显示出与渴望，情绪和暴露于药物使用触发因素的牢固的横断面瞬时关系。但是，压力等级与可卡因使用的发作之间的前瞻性关联充其量是弱的。 这种预期和意外发现的结合说明了可以量化和汇总进行分析的实时，现场行为数据的价值。