Stoops William W, Pike Erika, Hays Lon R, Glaser Paul E, Rush Craig R
University of Kentucky College of Medicine, Department of Behavioral Science, 140 Medical Behavioral Science Building, Lexington, KY, 40536-0086, USA; University of Kentucky College of Arts and Sciences, Department of Psychology, 110 Kastle Hall, Lexington, KY 40506-0044 USA; University of Kentucky College of Medicine, Department of Psychiatry, 245 Fountain Court, Lexington, KY 40509 USA.
University of Kentucky College of Arts and Sciences, Department of Psychology, 110 Kastle Hall, Lexington, KY 40506-0044 USA.
Pharmacol Biochem Behav. 2015 Feb;129:45-50. doi: 10.1016/j.pbb.2014.11.018. Epub 2014 Nov 29.
Naltrexone and bupropion, when administered alone in clinical trials, modestly reduce amphetamine use. Whether combining these drugs would result in greater reductions in methamphetamine taking relative to either drug alone is undetermined. This study examined the influence of naltrexone, bupropion and a naltrexone-bupropion combination on methamphetamine self-administration in humans. Seven subjects reporting recent illicit stimulant use completed a placebo-controlled, crossover, double-blind study in which the reinforcing, subject-rated and physiological effects of intranasal methamphetamine (0, 10 and 30 mg) were assessed during maintenance on placebo, naltrexone (50 mg), bupropion (300 mg/day), and naltrexone combined with bupropion. Methamphetamine maintained responding and produced prototypic subjective and physiological effects (e.g., increased ratings of good effects, elevated systolic blood pressure). Maintenance doses were well tolerated and generally devoid of effects. No maintenance condition reduced methamphetamine self-administration or systematically altered the subject-rated effects of methamphetamine. These outcomes demonstrate the robust behavioral effects of methamphetamine that could make it resistant to pharmacological manipulation. Although these outcomes indicate that this combination may be ineffective for managing methamphetamine use disorder, future work should evaluate longer maintenance dosing, individuals with different levels of amphetamine use, adding this combination to a behavioral platform and other pharmacotherapy combinations for reducing methamphetamine use.
在临床试验中单独使用时，纳曲酮和安非他酮能适度减少苯丙胺的使用。与单独使用这两种药物中的任何一种相比，联合使用这些药物是否会导致甲基苯丙胺使用量的更大减少尚未确定。本研究考察了纳曲酮、安非他酮以及纳曲酮 - 安非他酮组合对人体甲基苯丙胺自我给药的影响。七名报告近期使用过非法兴奋剂的受试者完成了一项安慰剂对照、交叉、双盲研究，在该研究中，评估了在服用安慰剂、纳曲酮（50毫克）、安非他酮（300毫克/天）以及纳曲酮与安非他酮联合用药期间，鼻内给予甲基苯丙胺（0、10和30毫克）的强化作用、受试者评分效应和生理效应。甲基苯丙胺维持反应并产生典型的主观和生理效应（例如，良好效应评分增加、收缩压升高）。维持剂量耐受性良好且一般无效应。没有任何维持条件能减少甲基苯丙胺的自我给药或系统性改变甲基苯丙胺的受试者评分效应。这些结果表明甲基苯丙胺具有强大的行为效应，这可能使其对药物操纵具有抗性。尽管这些结果表明这种组合可能对治疗甲基苯丙胺使用障碍无效，但未来的研究应评估更长时间的维持给药、不同苯丙胺使用水平的个体、将这种组合添加到行为治疗平台以及其他减少甲基苯丙胺使用的药物治疗组合。
