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Drug Alcohol Depend. 2010 Jun 1;109(1-3):20-9. doi: 10.1016/j.drugalcdep.2009.11.023. Epub 2010 Jan 25.

Randomized, double-blind, placebo-controlled trial of modafinil for the treatment of methamphetamine dependence.

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Department of Family Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.



To compare modafinil to placebo for reducing methamphetamine (MA) use, improving retention, and reducing depressive symptoms and MA cravings. Rates of adverse events and cigarette smoking with modafinil versus placebo were also compared.


Following a 2-week, non-medication lead-in period, 71 treatment-seeking MA-dependent participants were randomly assigned to modafinil (400mg once daily; N=34) or placebo (once daily; N=37) for 12 weeks under double-blind conditions. Participants attended clinic thrice-weekly to provide urine samples analyzed for MA-metabolite, to complete research assessments, and to receive contingency management and weekly cognitive behavioral therapy (CBT) sessions.


There were no statistically significant effects for modafinil on MA use, retention, depressive symptoms, or MA cravings in pre-planned analyses. Outcomes for retention and MA use favored modafinil in a post hoc analysis among participants with low CBT attendance and among participants with baseline high-frequency of MA use (MA use on >18 of past 30 days), but did not reach statistical significance in these small subgroups. Modafinil was safe and well tolerated and did not increase cigarette smoking.


Modafinil was no more effective than placebo at 400mg daily in a general sample of MA users. A post hoc analysis showing a trend favoring modafinil among subgroups with baseline high-frequency MA use and low CBT attendance suggests that further evaluation of modafinil in MA users is warranted.

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