Review of: Gray KM et al, Drug and Alcohol Dependence 2017;177:249–257

N-acetylcysteine (NAC) is an over-the-counter supplement related to the amino acid cysteine. In addition to its use as an antidote for acetaminophen poisoning, it has shown evidence of efficacy in some psychiatric disorders. For substance use disorders, its primary mechanism of action is the reversal of glutamate dysregulation, theoretically reducing vulnerability to relapse. A 2012 study of 116 adolescents with cannabis use disorder (CUD) found that subjects randomly assigned to 1200 mg of NAC were twice as likely to have cannabis-negative urines than those taking placebo. This most recent study attempted to replicate these findings in adults.

In this 12-week double-blind randomized controlled trial, 302 treatment-seeking adult participants diagnosed with CUD were randomized to placebo or 1200 mg NAC, both prescribed twice daily. The primary outcome was the percent likelihood of a negative urine cannabinoid test (UCT). UCTs were collected at baseline and twice weekly throughout the trial. Both groups also received a contingency management intervention (escalating cash payments to positively reinforce attendance and abstinence) and weekly medication counseling. The majority of the participants were white and male.

The results were discouraging: After 12 weeks, patients assigned to NAC submitted no more cannabis-free samples (22.3%) than those taking placebo (22.4%). However, a post-hoc analysis found that the younger participants in the trial (ages 18–21) were twice as likely to produce a negative UCT when assigned to the NAC group compared with placebo—although this finding did not reach statistical significance (p = 0.187). Though the medication was well tolerated, a major limitation of the study was poor medication adherence (73% adherence to NAC, 72% placebo), which was not problematic in the adolescent study (95% NAC, 93% placebo).

CATR’s Take
NAC does not appear to be effective for CUD in adults, though it’s possible that adolescents respond better to this supplement. Given that it is cheap and well tolerated (and that there are no effective alternatives), you might consider offering NAC to adolescents who are having difficulty cutting down their cannabis use.