N-acetyl cysteine in the treatment of cannabis use disorder: A systematic review of clinical trials

Background and Aim: Cannabis is the most consumed illicit drug globally, with a high risk of developing cannabis use disorder (CUD). No approved pharmacological treatment exists for CUD, but N-Acetyl Cysteine (NAC) has shown promising results in different clinical studies. This study aims to conduct a systematic review of NAC clinical trials for the treatment of CUD. Methods: Systematic review of randomized controlled trials (RCTs) was conducted to determine the effect of NAC for the treatment of cannabis dependence/cannabis use disorder (CUD). Articles were electronically searched across different databases using PubMed, Google Scholar, EMBASE, Cochrane Library, Medline and PsycINFO from inception to June 2021. Several study characteristics, including study duration, sample size, study population and age group, intervention, adverse effects, and outcome measure were extracted. A PICO table was used for data extraction. Results: We included 08 RCTs in the qualitative analysis. The risk of bias (RoB) was assessed according to Cochrane RoB criteria, and a 5 point grading system according to the Oxford Centre for Evidence-Based Medicine was used to rate the methodological quality (level of evidence) of the included articles. Mild and well-tolerated adverse events were reported in the placebo and NAC group. Conclusions: The studies collectively offer mixed results, although the strength of the evidence available on which to make a recommendation is strong. NAC has shown to be effective in promoting abstinence, medication adherence and reducing cannabis use and craving among cannabis dependent users. This review also suggests recommendations for future research.