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SYSTEMATIC REVIEW article

Front. Pharmacol.
Sec. Neuropharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1462612

Effect of N-acetylcysteine on Craving in Substance Use Disorders (SUD): A Meta-analysis of Randomized Controlled Trials

Provisionally accepted
Micol Cuocina Micol Cuocina 1,2Giuseppe Aiello Giuseppe Aiello 1,2Pierfelice Cutrufelli Pierfelice Cutrufelli 3Martina Rampello Martina Rampello 3Laura Rapisarda Laura Rapisarda 1,2Alessandro Rodolico Alessandro Rodolico 3Giuseppina Cantarella Giuseppina Cantarella 1,4*Maria S. Signorelli Maria S. Signorelli 3Renato Bernardini Renato Bernardini 1,2
  • 1 Department Biomedical and Biotechnological Sciences (BIOMETEC), Section of Pharmacology, University of Catania, 95123 Catania, Italy;, Catania, Italy
  • 2 Clinical Toxicology Unit, University Hospital of Catania, 95123 Catania, Italy;, Catania, Italy
  • 3 Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, Via Santa Sofia 78, 95123 Catania, Italy, Catania, Italy
  • 4 University of Catania, Catania, Italy

The final, formatted version of the article will be published soon.

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

    Keywords: craving1, N-acetylcysteine2, SUD3, addiction4, drugs5

    Received: 10 Jul 2024; Accepted: 28 Aug 2024.

    Copyright: © 2024 Cuocina, Aiello, Cutrufelli, Rampello, Rapisarda, Rodolico, Cantarella, Signorelli and Bernardini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Giuseppina Cantarella, University of Catania, Catania, Italy

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.