Rush Craig R, Stoops William W, Hays Lon R
Department of Behavioral Science, University of Kentucky College of Medicine, College of Medicine Office Building, Lexington, KY 40536-0086, USA.
Drug Alcohol Depend. 2009 Jan 1;99(1-3):261-71. doi: 10.1016/j.drugalcdep.2008.08.009. Epub 2008 Oct 15.
Agonist replacement therapies are effective for managing substance abuse disorders including nicotine and opioid dependence. The results of preclinical laboratory studies and clinical trials indicate that agonist replacements like D-amphetamine may be a viable option for managing cocaine dependence. This experiment determined the physiological and behavioral effects of cocaine during D-amphetamine maintenance in seven cocaine-dependent participants. We predicted cocaine would be well tolerated during D-amphetamine maintenance. We also predicted D-amphetamine would attenuate the behavioral effects of cocaine. After 3-5 days of D-amphetamine maintenance (0, 15, and 30 mg/day), volunteers were administered ascending doses of cocaine (4, 30, 60 mg, i.n.) within a single session. Cocaine doses were separated by 90 min. Cocaine produced prototypical physiological (e.g., increased heart rate, blood pressure, and body temperature) and subject-rated (e.g., increased ratings of Good Effects) effects. During maintenance on the highest D-amphetamine dose, the heart rate increasing effects of cocaine were larger than observed during placebo maintenance. These effects were not clinically significant and no unexpected or serious adverse events were observed. D-amphetamine attenuated some of the subject-rated effects of cocaine. These results are concordant with those of previous preclinical studies, human laboratory experiments and clinical trials, further suggesting that agonist replacement therapy may be a viable strategy for managing cocaine abuse. Additional research in humans is needed to determine whether D-amphetamine attenuates the effects of cocaine under different experimental conditions (e.g., higher cocaine doses) and behavioral arrangements (e.g., drug self-administration or discrimination).
激动剂替代疗法对于治疗包括尼古丁和阿片类药物依赖在内的物质使用障碍有效。临床前实验室研究和临床试验结果表明，像右旋苯丙胺这样的激动剂替代物可能是治疗可卡因依赖的一个可行选择。本实验确定了在7名可卡因依赖参与者中，右旋苯丙胺维持治疗期间可卡因的生理和行为效应。我们预测在右旋苯丙胺维持治疗期间，可卡因会有良好的耐受性。我们还预测右旋苯丙胺会减弱可卡因的行为效应。在右旋苯丙胺维持治疗3 - 5天（0、15和30毫克/天）后，志愿者在单个疗程内接受递增剂量的可卡因（4、30、60毫克，经鼻内给药）。可卡因剂量间隔90分钟。可卡因产生了典型的生理效应（如心率、血压和体温升高）以及受试者评定的效应（如“良好效应”评分增加）。在最高剂量的右旋苯丙胺维持治疗期间，可卡因引起的心率增加效应比安慰剂维持治疗期间观察到的更大。这些效应在临床上不显著，且未观察到意外或严重不良事件。右旋苯丙胺减弱了可卡因的一些受试者评定效应。这些结果与先前的临床前研究、人体实验室实验和临床试验结果一致，进一步表明激动剂替代疗法可能是治疗可卡因滥用的一种可行策略。需要在人体中进行更多研究，以确定右旋苯丙胺在不同实验条件（如更高的可卡因剂量）和行为安排（如药物自我给药或辨别实验）下是否会减弱可卡因的效应。
