From a neuroscientific point of view, one of the unique archetypes of substance use disorders is its road to relapse, in which the reward system plays a crucial role. Studies on the neurobiology of substance use disorders have highlighted the central role of a protein belonging to the Fos family of transcription factors, ΔFosB. Relying on the roles ΔFosB plays in the pathophysiology of substance use disorders, we endeavour to present some evidence demonstrating that N-acetylcysteine, a low-cost and well-tolerated over-the-counter medicine, may influence the downstream pathway of ΔFosB, thereby serving as a treatment strategy to mitigate the risk of relapse in cases of substance use.