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.