Effects of naltrexone on the subjective response to amphetamine in healthy volunteers

While dopaminergic mechanisms in amphetamine-taking behavior have been extensively studied, the contribution of the endogenous opioid system is less clear. We assessed the effects of an opioid antagonist, naltrexone (50 mg), on the subjective response to an oral dose of dexamphetamine (30 mg) in 12 healthy volunteers in a double-blind, placebo-controlled design. Volunteers received a total of 4 combinations of the study preparation (placebo-naltrexone, placebo-amphetamine) over 4 occasions with 1-week intervals. The primary objective of the study was to evaluate the effect of pretreatment with naltrexone on the subjective response to amphetamine. This was measured using a Visual Analog Scale, assessing the subjective effects over 7 hours. The secondary objective was to measure the effects of naltrexone on behavioral and physiologic responses to amphetamine. This was measured by blood pressure, heart rate, skin conductance, and speed of reading at the end of each session. Amphetamine produced significant effects on subjective arousal when compared to placebo after 1 hour (P < 0.001) and continued to be evident until 7 hours. Pretreatment with naltrexone significantly attenuated the subjective effects of amphetamine (P < 0.05), and this effect was time-dependent with a reduction from the 3-hour time point. Naltrexone did not influence the behavioral and physiologic effects of amphetamine in this sample. The results provide preliminary evidence that naltrexone may reduce the reinforcing effects of amphetamine via modulation of the opioid system. The potential of naltrexone as an adjunct pharmaceutical for the treatment of amphetamine dependence is promising and needs to be investigated further.