Objective: Treatment with N-acetylcysteine (NAC) is believed to reduce the clinical symptoms among individuals with substance abuse or dependence. We conducted a meta-analysis of randomized controlled trials to evaluate the effectiveness of NAC in treating substance abuse and dependence. Methods: PubMed, EMBASE, ClinicalTrials.gov registry, and the Cochrane Library were searched for trials published before June 2020. Results: A total of 16 trials were analyzed. The treatment effectiveness domains assessed in this study were craving and depressive symptoms, withdrawal syndrome, adverse events, and smoking frequency. Standardized mean difference (SMD), weighted mean difference (WMD), and odds ratio (OR) were used for evaluation where appropriate. A significant decrease in craving symptoms was observed in the NAC treatment group compared with the control group (SMD, -0.67; 95% confidence interval [CI], -1.21 to 0.21). When withdrawal and depressive symptoms were considered as a single domain, the NAC treatment group demonstrated a significantly higher overall improvement than the control group (SMD, -0.35; 95% CI, -0.64 to -0.06). No between-group differences in term of the OR of adverse events (OR, 1.18; 95% CI, 0.68 to 2.06) and a non-significant trend toward reduction in smoking frequency was observed in the NAC treatment group compared with the control group (WMD, -3.09; 95% CI, -6.50 to 0.32). Conclusion: NAC provides certain noticeable benefits in attenuating substance craving and might help alleviate depressive symptoms and withdrawal syndrome. Precautious measures should be considered when using NAC although no difference in adverse effects was found between NAC treatment and control group.
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