Sleep disruption in stimulant use disorder is not merely an uncomfortable side effect — it is one of the most powerful predictors of relapse, making it a critical and under-addressed therapeutic target. For the millions managing cocaine or methamphetamine use disorders, persistent insomnia and circadian dysregulation can persist for months after cessation, creating a neurobiological environment that actively undermines recovery. This review attempts to systematically map what pharmacology currently offers for that problem.
Drawing on 18 studies encompassing 678 participants — 11 focused on cocaine use disorder (CUD) and seven on methamphetamine use disorder (MUD) — this PRISMA-compliant review evaluated agents across both conditions using rigorous sleep measurement tools. For CUD, modafinil emerged as a particularly interesting candidate, showing preliminary associations with improved sleep parameters and, notably, higher abstinence rates, suggesting a possible dual benefit on recovery and sleep architecture. Buprenorphine and suvorexant also showed early promise in CUD. Results for mirtazapine, cannabidiol, lorazepam, tiagabine, and lisuride were inconsistent. For MUD, mirtazapine and modafinil demonstrated modest early benefits, while quetiapine and suvorexant showed signal in smaller samples.
The findings are directionally useful but must be interpreted carefully. The aggregate sample of 678 across 18 studies is modest, meaning most individual trials were underpowered to detect subtle sleep-stage effects. The moderate-to-high methodological quality is reassuring, but the heterogeneity of outcome measures across studies makes head-to-head comparisons difficult. Modafinil's dual association with sleep improvement and abstinence is the most clinically provocative signal here — it may reflect a common mechanism involving dopaminergic stabilization rather than independent effects. Suvorexant's appearance in both CUD and MUD cohorts is also worth tracking, given its orexin-receptor mechanism, which has theoretical relevance to the arousal dysregulation seen in stimulant withdrawal. This review is confirmatory of the field's early-stage status rather than paradigm-shifting, but it provides a useful evidence scaffold for future adequately powered trials.