Reducing both glutamatergic and dopaminergic drive in the nucleus accumbens may offer complementary mechanisms by which to reduce drug cravings. This 8-week study sought to examine the efficacy of a combination of a glutamate modulator, N-acetyl cysteine (NAC), plus the opioid antagonist, naltrexone, compared to placebo in the treatment of methamphetamine dependence. Thirty-one subjects with methamphetamine dependence (mean age 36.8 ± 7.12 years; 29% female) were randomly assigned in a 1:1 fashion to NAC plus naltrexone or placebo and returned for one post-baseline visit. The Penn Craving Scale was the primary outcome measure. Self-report methamphetamine use frequency and urine toxicology were secondary measures. NAC plus naltrexone failed to demonstrate statistically significant differences from placebo on primary and secondary outcomes. The current study failed to demonstrate greater efficacy for NAC plus naltrexone compared to placebo. Given the small sample size, the statistical power to detect significant effects of active treatment versus placebo was limited. The question of whether a larger, well-powered sample would have detected differences between NAC plus naltrexone and placebo deserves further examination.
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