Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 May 31;19(2):282-293.
doi: 10.9758/cpn.2021.19.2.282.

Effectiveness of N-acetylcysteine in Treating Clinical Symptoms of Substance Abuse and Dependence: A Meta-analysis of Randomized Controlled Trials

Chung-Ting Chang  1 , Pei-Ju Hsieh  2 , Hsin-Chien Lee  3   4 , Chun-Hong Lo  1 , Ka-Wai Tam  5   6   7   8   9 , El-Wui Loh  5   6   7   10
Affiliations

Effectiveness of N-acetylcysteine in Treating Clinical Symptoms of Substance Abuse and Dependence: A Meta-analysis of Randomized Controlled Trials

Chung-Ting Chang et al. Clin Psychopharmacol Neurosci. .

Abstract

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.

Keywords: Acetylcysteine; Addiction; Craving; Depression; Substance; Withdrawal..

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1
Fig. 1
Flowchart of trials selection. NAC, N-acetylcysteine.
Fig. 2
Fig. 2
Forest plot of comparison: N-acetylcysteine (NAC) versus control; outcome: craving symptoms. SD, standard deviation; Std, standardized; 95% CI, 95% confidence interval; IV, inverse variance.
Fig. 3
Fig. 3
Forest plot of comparison: N-acetylcysteine (NAC) versus control; outcomes: withdrawal syndrome. SD, standard deviation; Std, standardized; 95% CI, 95% confidence interval; IV, inverse variance.
Fig. 4
Fig. 4
Forest plot of comparison: N-acetylcysteine (NAC) versus control; outcome: depressive symptoms. SD, standard deviation; Std, standardized; 95% CI, 95% confidence interval; IV, inverse variance.
Fig. 5
Fig. 5
Forest plot of comparison: N-acetylcysteine (NAC) versus control; outcome: any adverse event. 95% CI, 95% confidence interval; M-H, Mantel-Haenszel.
Fig. 6
Fig. 6
Forest plot of comparison: N-acetylcysteine (NAC) versus control; outcome: smoking frequency. SD, standard deviation; 95% CI, 95% confidence interval; IV, inverse variance.
Fig. 7
Fig. 7
Forest plot of comparison: N-acetylcysteine (NAC) versus control; outcomes of specific substances: (1) alcohol craving, (2) tobacco withdrawal, and (3) depression among smokers. SD, standard deviation; Std, standardized; 95% CI, 95% confidence interval; IV, inverse variance.
See this image and copyright information in PMC

References

    1. Center for Behavioral Health Statistics and Quality, author. Key substance use and mental health indicators in the United States: results from the 2015 national survey on drug use and health. Center for Behavioral Health Statistics and Quality; Rockville (MD): 2016. Report No.: SMA 16-4984, NSDUH Series H-51)
    1. Prado E, Maes M, Piccoli LG, Baracat M, Barbosa DS, Franco O, et al. N-acetylcysteine for therapy-resistant tobacco use disorder: a pilot study. Redox Rep. 2015;20:215–222. doi: 10.1179/1351000215Y.0000000004. - DOI - PMC - PubMed
    1. Olive MF. Metabotropic glutamate receptor ligands as potential therapeutics for addiction. Curr Drug Abuse Rev. 2009;2:83–98. doi: 10.2174/1874473710902010083. - DOI - PMC - PubMed
    1. Hopf FW. Do specific NMDA receptor subunits act as gateways for addictive behaviors? Genes Brain Behav. 2017;16:118–138. doi: 10.1111/gbb.12348. - DOI - PMC - PubMed
    1. McCullumsmith RE, Sanacora G. Regulation of extrasynaptic glutamate levels as a pathophysiological mechanism in disorders of motivation and addiction. Neuropsychopharmacology. 2015;40:254–255. doi: 10.1038/npp.2014.218. - DOI - PMC - PubMed