Project Summary/Abstract The US opioid epidemic costs over $1.5T and over 75,000 deaths annually. An understudied risk factor for opioid use disorder (OUD) and its treatment is the importance of sleep and circadian rhythms (CR). Opioids impact sleep quality in a fashion that inhibits recovery, and sleep remains a critical factor even when patients enter treatment: the two most efficacious medications for OUD (MOUD) also cause sleep problems that contribute to suboptimal outcomes. To address the enormous costs of the opioid epidemic, it is essential to understand the mechanisms underlying the relationship between MOUD, poor sleep, and negative outcomes. Thus, our central hypothesis is that examination of sleep and circadian phenotypes, will help to identify individuals on MOUD who will benefit from specific interventions. Characterization of the bidirectional interplay between sleep behaviors, sleep architecture, circadian rhythms, and neurocognitive measures in individuals on MOUD is a crucial first step in identifying potential mechanisms or modifiable variables to improve MOUD outcomes. Identifying the specific type of sleep/circadian disruption by MOUD may highlight adjunctive treatment options to address the relevant sleep problem (e.g., cognitive behavioral therapy for insomnia). Moreover, MOUDs disrupt sleep, but it is not known whether this is via alterations of CR or alterations of sleep behavior/architecture. Sleep/CR science provides experimental methods for separating circadian timing from sleep physiology in the form of the 90-minute day. Prior work highlights neurocognitive phenotypes, craving and emotion regulation (ER), that are critical for successful MOUD outcomes. Cravings are both an OUD symptom and frequent predictor of relapse. Sleep quality affects craving possibly through positive and negative affect, emphasizing that ER is of critical concern with MOUD, as patients report an inability to regulate emotions as a primary motivation for use and for relapse. Poor sleep is associated with diminished ER. In 100 individuals on MOUD we will 1) evaluate (a) naturally occurring sleep patterns using activity monitoring for one week and (b) sleep physiology through polysomnographic recording in the sleep lab to contribute to the common aim across research sites and to provide descriptive analyses; 2) examine sleep and circadian phenotypes using variables collected via actigraphy, PSG, and the 90-min day protocol to examine associations of these phenotypes with neurocognitive mechanisms that may impact outcome of OUD treatment including craving and emotion regulation; and 3) use qualitative methods to investigate the acceptability, feasibility, and perceived utility of interventions targeting the specific mechanistic relationships hypothesized. In summary, we plan a comprehensive examination of novel pathways between sleep/circadian rhythms and neurocognitive factors —craving and emotion regulation—critical to success in MOUD as putative mechanisms underpinning the association of poor sleep and suboptimal treatment outcomes.

PROJECT NARRATIVE The opioid epidemic in the US continues at a cost of over $1.5T and over 75,000 deaths annually. Poor sleep is a major risk factor that both influences opioid problems and is influenced by opioid treatments and opioids themselves. Improved understanding of mechanisms that link sleep and opioid-related factors, such as changes in craving and/or ability to regulate emotions may highlight new opportunities for targeted treatment.