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.

在实验动物中，压力已被证明会诱发药物寻找的恢复。实验模型是先前获得性药物自我给药消失后操作行为的恢复。以足部电击形式出现的生理压力一直被证明会导致大鼠重新寻求海洛因和可卡因（Shaham and Stewart, 1995; Erb et al., 1996; Shaham, 1996）。这种应激诱导的恢复可被α -2肾上腺素能受体激动剂可乐定阻断（Erb等人，2000；Shaham等人，2000；Highfield等人，2001）。α -2激动剂可能作用于应激诱导复发的一些最终共同途径，与多种药物滥用有关。我们在一项实验室研究中测试了可乐定对人类可卡因使用者的压力和线索诱导的渴望的影响，发现可乐定0.1和0.2 mg显著减弱了对压力剧本的反应；仅在较高的可乐定剂量（0.2 mg）下，对药物提示脚本的反应性显著减弱。因此，可乐定可以减少吸毒者对可卡因的渴望和一些生理反应，在经历压力情况或提醒他们吸毒的情况下。