Sleep and circadian rhythm phenotypes and mechanisms associated with opioid use disorder treatment outcomes

Opioid use disorder (OUD) is a rapidly escalating public health crisis with recent evidence suggesting that close to 70% of drug overdoses involved opioids in the last year. Although many individuals seek treatment for OUD over half return to use despite being maintained on a medication for opioid use disorder (MOUD), underscoring

the critical need to identify factors that are associated with OUD reoccurrence. Chronic opioid use has been linked to disturbances in sleep continuity and architecture, increased risk of sleep disordered breathing (SDB), and abnormalities in proxy measures of circadian rhythms. However, less is known about the longitudinal

association of sleep/circadian phenotypes with non-medical opioid use among individuals in OUD treatment, and malleable pathways that may account for these associations. Such knowledge is critical to informing translational research and the development of novel interventions aimed at improving sleep, circadian rhythms, and OUD

outcomes. The proposed observational, longitudinal study will capitalize on existing collaborations with community-based providers to determine the association of sleep duration, sleep architecture, SDB, and proxy measures of circadian rhythms with illicit opioid use during treatment, and potential pathways (e.g., positive and

negative affect) that may influence these relationships. Participants (N = 130) will be enrolled in buprenorphine or methadone treatment and complete a 6-month longitudinal study wherein they will complete overnight, in-lab polysomnography (PSG) sessions three times to assess changes over time in sleep metrics (e.g., total sleep

time, sleep architecture, SDB). Before and after PSG sessions, we will collect saliva samples from participants to determine diurnal cortisol patterns. Participants will also be fitted with a wrist-worn actigraphy device to further quantify sleep and circadian rest activity rhythms. At baseline and during the final week of each month of

treatment, participants will complete a week-long “data burst” that includes ecological momentary assessments of affect, craving, and stress. Participants will complete urine toxicology screens and self-report on their drug use at the end of each data burst. Specific aims of the study are to (Aim 1) determine the bi-directional

association of circadian RARs and diurnal cortisol patterns with non-medical opioid use, (Aim 2) investigate whether sleep duration and architecture over the course of treatment are associated with non-medical opioid use, and (Aim 3) examine (a) associations of MOUD use with SDB, and (b) whether SDB is associated with low

positive affect and high negative affect. We will also explore whether clinically significant sleep and circadian rhythm phenotypes are associated with low positive affect, high negative affect, and non-medical opioid use, and whether affective processes mediate the association of sleep/circadian rhythm phenotypes and opioid use.

Findings from this project will enhance our understanding of specific sleep and circadian rhythms parameters implicated in OUD, and the relationships among sleep phenotypes, affective processes, and non-medical opioid use. This highly rigorous study will shed light on clinically relevant endpoints for future intervention trials.