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Naltrexone and Bupropion Alone or Combined Do Not Alter the Reinforcing Effects of Intranasal Methamphetamine

机译:纳曲酮和安非他酮(单独或联合使用)不会改变鼻内甲基苯丙胺的增强作用

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摘要

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.
机译:在临床试验中单独使用纳曲酮和安非他酮时,可适度减少苯丙胺的使用。与单独使用这两种药物相比,将这些药物组合使用是否会导致甲基苯丙胺的服用量进一步减少尚不确定。这项研究检查了纳曲酮,安非他酮和纳曲酮-安非他酮组合对人体中甲基苯丙胺自我给药的影响。七名报告最近使用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,该研究在维持期间对安慰剂,纳曲酮(0,10和30 mg)鼻内甲基苯丙胺(0、10和30 mg)的增强,受试者评定和生理学作用进行了评估( 50毫克),安非他酮(300毫克/天)和纳曲酮联合安非他酮。甲基苯丙胺维持反应并产生原型的主观和生理效应(例如,良好效果等级的提高,收缩压的升高)。维持剂量具有良好的耐受性,通常没有影响。没有维持条件会减少甲基苯丙胺的自我给药或系统地改变甲基苯丙胺的受试者疗效。这些结果表明,甲基苯丙胺具有强大的行为作用,可以使其对药理操作具有抵抗力。尽管这些结果表明该组合可能无法有效管理甲基苯丙胺使用障碍,但未来的工作应评估更长的维持剂量,苯丙胺使用水平不同的个体,并将该组合添加到行为平台和其他药物治疗组合中以减少甲基苯丙胺的使用。

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