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. 2024 Sep 6:15:1462612.
doi: 10.3389/fphar.2024.1462612. eCollection 2024.

Effect of N-acetylcysteine on craving in substance use disorders (SUD): a meta-analysis of randomized controlled trials

Micol Cuocina #  1   2 , Giuseppe Aiello #  1   2 , Pierfelice Cutrufelli  3 , Martina Rampello  3 , Laura Rapisarda  1   2 , Alessandro Rodolico  4 , Giuseppina Cantarella  1 , Maria Salvina Signorelli  3 , Renato Bernardini  1   2
Affiliations

Effect of N-acetylcysteine on craving in substance use disorders (SUD): a meta-analysis of randomized controlled trials

Micol Cuocina et al. Front Pharmacol. .

Abstract

Background: N-acetyl cysteine (NAC) appears promising as a treatment in patients with substance use disorder (SUD) as it helps rebalance glutamate levels in the central nervous system (CNS). Basal concentrations of glutamate are indeed reduced in SUD patients but increased during craving.

Materials and methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). We assessed whether NAC reduce craving rating as compared to a placebo in SUD patients. Secondary outcomes were withdrawal symptoms (WS), side effects (SE) and drop-outs. Estimates are presented as standardized mean differences (SMD) or risk ratio (RR) with 95% confidence interval (CI).

Results: Eleven RCTs were included. NAC reduced craving rating (SMD -0.61 (-1.17, -0.06), p = 0.03, I2 = 85%), with no differences in the subgroup analysis according to the drug addiction (alcohol, cocaine, poly-drugs, amphetamine, nicotine) (p = 0.98). Among the secondary outcomes, for WS data showed no significant difference between groups (SMD -0.18 (-0.43, 0.08), p = 0.17); for SE no substantial difference was observed between the two treatment groups (RR = 1.06 (0.89-1.27), p = 0.52, I2 = 0%); for dropouts the results are in favor of the placebo but no statistically significant (RR 1.17 (0.85, 1.61), p = 0.34; I2 = 0%).

Conclusion: NAC seem to reduce craving rating in SUD patients, but evidence is weak. More studies are needed to confirm this finding.

Keywords: N-acetylcysteine; SUD; addiction; craving; drugs.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
PRISMA flowchart graphically describes the process of screening, selection and inclusion of articles. Abbreviation. PRISMA: Preferred Reporting Items for Systematic reviews and Meta-Analyses.
FIGURE 2
FIGURE 2
Forest plot reporting the differences in craving ratings in patients with SUD and treated with NAC as compared to Placebo. Abbreviation. SUD, Substances Use Disorder; NAC, N-acetylcysteine; CI, confidence interval; IV, Inverse Variance.
FIGURE 3
FIGURE 3
Trial Sequential Analysis on Craving ratings. Abbreviation. RE, random effect; RRR, relative risk reduction.
See this image and copyright information in PMC

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