Investigating mechanisms underpinning outcomes in people on opioid agonist treatment for OUD: Disentangling sleep and circadian rhythm influences on craving and emotion regulation

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.

Grant Number: 5R01DA059469-03
NIH Institute/Center: NIH
Principal Investigator: Mary Carskadon