N-acetylcysteine (NAC) for methamphetamine dependence: A randomised controlled trial

Randomized, placebo-controlled trial in adults with methamphetamine dependence who were seeking to reduce use. The active NAC arm included 76 participants; 77 were assigned to placebo. Participants were recruited across three Australian sites and stratified by site, sex, and injecting versus non-injecting methamphetamine use.

Participants in the active arm received oral N-acetylcysteine (NAC) 2400 mg/day for 12 weeks, given as two 600 mg capsules twice daily in the morning and evening. The comparison was matched placebo capsules.

NAC did not improve methamphetamine use outcomes versus placebo over 12 weeks. Methamphetamine use days fell in both groups, but the between-group difference was not significant (0.5 days, 97.5% CI -3.4 to 4.3), and mean reduction in use days was similar: placebo 7.3 [1.2] versus NAC 6.8 [1.2]. NAC also showed no significant benefit for methamphetamine-positive oral fluid samples, craving, severity of dependence, withdrawal, hostility, depression, or suicidality. Adverse events were similar overall, with 11 serious adverse events affecting 10 participants (6 on NAC, 4 on placebo).

The trial tested a single NAC dose for a relatively short 12-week period, which limits inference about longer-term treatment effects. Adherence was only moderate, with a reported median of about 66%, and the sample was drawn from adults seeking to reduce methamphetamine use at three Australian sites, which may limit generalizability.