The Insomnia-Addiction Positive Feedback Loop: Role of the Orexin System

Jennifer E. Fragale, Morgan H. James, Jorge A. Avila, Andrea M. Spaeth, R. Nisha Aurora, Daniel Langleben, Gary Aston-Jones

Research output: Contribution to journalArticlepeer-review


Significant sleep impairments often accompany substance use disorders (SUDs). Sleep disturbances in SUD patients are associated with poor clinical outcomes and treatment adherence, emphasizing the importance of normalizing sleep when treating SUDs. Orexins (hypocretins) are neuropeptides exclusively produced by neurons in the posterior hypothalamus that regulate various behavioral and physiological processes, including sleep-wakefulness and motivated drug taking. Given its dual role in sleep and addiction, the orexin system represents a promising therapeutic target for treating SUDs and their comorbid sleep deficits. Here, we review the literature on the role of the orexin system in sleep and drug addiction and discuss the therapeutic potential of orexin receptor antagonists for SUDs. We argue that orexin receptor antagonists may be effective therapeutics for treating addiction because they target orexin's regulation of sleep (top-down) and motivation (bottom-up) pathways.

Original languageEnglish (US)
Pages (from-to)117-127
Number of pages11
JournalFrontiers of Neurology and Neuroscience
StatePublished - 2021

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Neurology


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