Abstract

Objectives: To evaluate the clinical safety and efficacy of N-acetylcysteine (NAC) in prolonging abstinence time among adults with cocaine base paste (CBP) use disorder. Methods: A phase II, randomised, double-blind, placebo-controlled clinical trial, with a parallel group design, was conducted in CBP use disorder treatment-seeking adults in public outpatient mental health units in the province of Concepción, Chile (n = 140). Participants were randomised to receive daily doses of 2400 mg of NAC or placebo. They were followed for 4 weeks, attending twice-weekly to assess medication-related evaluate adverse effects and to measure abstinence in terms of the days until first new CBP use after study entry. Statistical analysis was performed using the R statistical program, and survival analysis was conducted using Kaplan-Meier. Results: NAC was a safe treatment without a severe adverse reaction, but it was not better than placebo to prolong the CBP abstinence time (P = 0.12). However, when considering a previous abstinence time of more than 7 days, differences were found in the NAC treatment arm, with better survival in the subgroup that had greater prior abstinence (P = 0.0052), which was not observed in the placebo treatment arm (P = 0.12). Conclusions: Although NAC did not demonstrate superiority over placebo in prolonging CBP abstinence, evidence suggests that its efficacy may be influenced by prior abstinence. These findings underscore the need for further research into how prior abstinence affects NAC efficacy, while also supporting the notion that NAC may be more effective for relapse prevention than for initiating abstinence. © © 2025 American Society of Addiction Medicine.