# Evaluating the Role of the Orexin System in Circadian Rhythms of Sleep and Stress in Persons on Medication-Assisted Treatments for Opioid Use Disorder

> **NIH NIH U01** · JOHNS HOPKINS UNIVERSITY · 2024 · $623,135

## Abstract

The opioid crisis continues to devastate the lives of countless people and communities across the United
States. For individuals with moderate to severe opioid use disorder (OUD), medication-assisted treatments
(MATs) such as oral methadone and extended-release naltrexone (XR-NTX) are the gold standard in initiating
and maintaining long-term recovery. Still, many patients struggle with persistent sleep disturbance and stress
reactivity in the early stages of recovery, which drive relapse behaviors. Research on sleep disturbance and
the circadian rhythms of stress in the human experience of OUD recovery is scarce. This proposal constitutes
a novel mechanistic approach to understanding the role of the orexin system in sleep disturbance and
circadian rhythms of stress in OUD patients who are maintained on either oral methadone or XR-NTX and are
early in recovery. The scientific premise of this study is based on a rich preclinical literature demonstrating that
increased orexin signaling disrupts sleep, increases stress via the hypothalamic-pituitary-adrenal axis (HPA-
axis), and drives drug seeking behaviors in rodent models. The proposed study will determine whether the
FDA-approved sleep medication, suvorexant (SUVO)—a dual orexin-receptor antagonist—improves sleep
continuity and decreases diurnal measures of stress, and whether improvement of sleep/stress processes
translates to improved OUD treatment outcomes including reduced opioid relapse. To execute this study, we
have assembled an exceptional team of experts in OUD, MATs, sleep, stress, and ambulatory monitoring. This
study will recruit persons with OUD who have been abstinent from illicit opioids for 3-6 weeks, report sleep
disturbance, and are utilizing a stable dose of oral methadone (n=100) or XR-NTX (n=100). The study will
consist of baseline measurements for 7 days (week 0) followed by randomization to either 20mg SUVO or
placebo for an 8-week, double-blind randomized-controlled trial. Participants will undergo daily ambulatory
monitoring of sleep and daytime activity throughout the study using wrist-worn actigraphy and electronic sleep
diaries (weeks 0-8). Moreover, participants will undergo more intensive Data Bursts during study weeks 0
(baseline), 1, 4, and 8, which consist of four-times-daily ecological momentary assessments (EMA) of self-
reported stress, craving, and affect, and diurnal salivary cortisol. Primary analyses 1 and 2 examine the effect
of SUVO on total sleep time (TST), wake after sleep onset (WASO), and diurnal self-reported stress and
separately in patients on oral methadone or XR-NTX, respectively. Primary analysis 3 examines the effect of
TST, WASO, and diurnal self-reported stress and salivary cortisol on opioid relapse, across MATs. Exploratory
analyses include the effect of SUVO on opioid relapse and treatment retention, and the effect of MAT status on
TST, WASO, and diurnal self-reported stress and salivary cortisol within the placebo condition. The proposed...

## Key facts

- **NIH application ID:** 11137284
- **Project number:** 4U01HL150835-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Patrick Finan
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $623,135
- **Award type:** 4N
- **Project period:** 2019-09-23 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11137284

## Citation

> US National Institutes of Health, RePORTER application 11137284, Evaluating the Role of the Orexin System in Circadian Rhythms of Sleep and Stress in Persons on Medication-Assisted Treatments for Opioid Use Disorder (4U01HL150835-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11137284. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*