The therapeutic effect of N-acetylcysteine as an add-on to methadone maintenance therapy medication in outpatients with substance use disorders: A randomized, double-blind, placebo-controlled clinical trial.

Objective: Patients with substance use disorders (SUD) under methadone maintenance therapy (MMT) are susceptible to a number of complications (psychological and metabolic disorders). Evidence studies have shown the roles of the glutamatergic system in addiction. N-Acetylcysteine (NAC) enhances extracellular glutamate, and is effective in the treatment of neuropsychiatric disorders. We assessed oral NAC as an add-on to MMT medication for the treatment of SUD.

Methods: In the current randomized, double-blind, placebo-controlled clinical trial, outpatients with SUD under MMT who were 18-60 years old received 2400 mg/day NAC (n = 30) or placebo (n = 30) for 12 weeks. Psychological status and metabolic biomarkers were assessed at baseline and the end of the trial.

Results: Compared with the placebo group, NAC treatment resulted in a significant improvement in depression score (β -2.36; 95% CI, -3.97, -0.76; p = .005), and anxiety score (β -1.82; 95% CI, -3.19, -0.44; p = .01). Furthermore, NAC treatment resulted in a significant elevation in total antioxidant capacity levels (β 72.28 mmol/L; 95% CI, 11.36, 133.19; p = .02), total glutathione (GSH) levels (β 81.84 μmol/L; 95% CI, 15.40, 148.28; p = .01), and a significant reduction in high-sensitivity C-reactive protein levels (β -0.89 mg/L; 95% CI, -1.50, -0.28; p = .005), and homeostasis model of assessment-insulin resistance (β -0.33; 95% CI, -0.65, -0.009; p = .04), compared with the placebo group.

Conclusion: In the current study, improvement in depression and anxiety symptoms as well as some metabolic profiles with NAC treatment for 12 weeks in outpatients with SUD under MMT was detected.