The findings suggest that modafinil improves learning in MA-dependent participants, possibly by enhancing neural function in regions important for learning and cognitive control. After controlling for performance differences, MA-dependent participants showed a greater effect of modafinil on brain activation in bilateral insula/ventrolateral prefrontal cortex and anterior cingulate cortices than control participants. Modafinil boosted learning in MA-dependent participants, bringing them to the same performance level as control subjects the control group did not show changes in performance with modafinil. Under placebo conditions, MA-dependent participants showed worse learning performance than control participants. Modafinil (200 mg) and placebo were administered orally (one single dose each), in counterbalanced fashion, 2 h before each of two testing sessions. We therefore conducted a randomized, double-blind, placebo-controlled, cross-over study, using functional magnetic resonance imaging, to examine the effects of modafinil on learning and neural activity related to cognitive function in abstinent, MA-dependent, and healthy control participants. Modafinil has been shown to improve cognitive performance in neuropsychiatric patients and healthy volunteers. Therefore, medications that improve cognition in these subjects may improve the success of therapy for their addiction, especially when cognitive behavioral therapies are used. Methamphetamine (MA)-dependent individuals exhibit deficits in cognition and prefrontal cortical function.

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