Sleep regulates drug seeking and relapse – a perspective

Mol Psychiatry. 2026 Feb 1. doi: 10.1038/s41380-025-03406-1. Online ahead of print.

ABSTRACT

The recent decade has seen an increasing recognition of the importance of sleep in substance use disorders (SUD) in both research and clinical settings. Not only is sleep disturbance a common comorbidity in SUD, but it may provide a causal link and druggable targets for complementary treatment. The interpersonal variation in sleep also provides opportunities for developing biomarkers and individualized medicine. This review is focused on the key neurotransmitter and neuromodulator systems through which sleep loss may bias reward seeking, increasing the risks for initial drug exposure as well as relapse after drug withdrawal. The review summarizes sleep changes following acute or long-term drug exposure and withdrawal, and current understanding of sleep-mediated regulation of glutamatergic, dopaminergic, and peptidergic transmissions importantly indicated in SUD research.

PMID:41620581 | DOI:10.1038/s41380-025-03406-1