Naltrexone and bupropion, alone or combined, do not alter the reinforcing effects of intranasal methamphetamine

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.