Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

A mechanistic study of the role of the orexin system and insomnia within a buprenorphine opioid use disorder treatment sample

Award Number: R01DA061265
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2025
PERIOD OF PERFORMANCE END DATE: 04/30/2030

Group Awards By:

View Award Description

A mechanistic study of the role of the orexin system and insomnia within a buprenorphine opioid use disorder treatment sample - Opioid use disorder (OUD) is a leading cause of death, demanding improvements in OUD treatments. Medica- tions for OUD are life-saving; increasing their consistent utilization is the most effective pathway forward to combat this public health crisis. However, after treatment engagement, multiple factors can hinder outcomes, such as sleep problems and neurofunctional impairment that can leave patients at persistent overdose risk. NIDA has promoted targeting the mechanisms underlying each individual patient's addiction as an avenue to advance precision medicine and improve treatment quality. Targeting the orexin system is one mechanism that could ultimately lead to improved treatments. The orexin system is hypothesized to be a predominant mecha- nism linking poor OUD outcomes with disturbances in sleep/wake cycles and with other orexin-activity effects on reward-related neurofunctional domains known to underlie OUD. Consistent with this advancing science, our group has identified how insomnia exists as part of a constellation of symptoms related to neurofunctional dysfunctions among buprenorphine-treatment patients. Thus, we propose that targeting insomnia by way of orexin perturbation shows high potential to advance OUD medication development, such as via identifying tar- gets for adjunctive relapse prevention therapeutics to medications for OUD. However, how the orexin system and insomnia engage neurobiological mechanisms in humans with OUD has not been investigated. Using in- novative dynamic causal modeling, our group has identified a neurocircuit connectivity (Anterior cingulate cor- tex (ACC) to Hippocampus) that is associated with drug cue driven attentional bias in individuals with OUD, making this a promising marker in the evaluation of potential relapse prevention therapeutics. We propose herein a mechanistic study where we will recruit OUD treatment patients receiving buprenorphine with and without clinically significant insomnia (N=100). We will experimentally manipulate the orexin system using lem- borexant, a dual orexin receptor antagonist, which our group has found to be safe and tolerable with buprenor- phine in our Phase 1 clinical trial. We will rigorously measure sleep (actigraphy) and fMRI-based brain connec- tivity before and after randomization to 14 days of placebo or lemborexant added to their ongoing buprenor- phine treatment. Building from our group's extensive preliminary data, we propose that the effective (direc- tional) connectivity of the ACC to Hippocampus pathway, with its overlapping system involvements related to orexin, drug use, and sleep, represents an optimal primary outcome for this mechanistic trial in response to RFA-DA-25-044. In Aim 1, we will identify differences in this baseline drug cue-elicited brain connectivity be- tween insomnia groups. In Aim 2, we will determine whether pharmacologic orexin antagonism attenuates this connectivity, regardless of insomnia status. These mechanistic findings will characterize the interplay between insomnia, orexin and OUD in a buprenorphine treatment sample to advance the development of personalized relapse prevention therapeutics which are urgently needed in the ongoing overdose crisis.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Drug Use and Addiction Research Programs	000	1	12/10/2025	NEW	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $465,669 )
2025	2025	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Drug Use and Addiction Research Programs	000	1	7/11/2025	NEW	$465,669
2025	2025	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Drug Use and Addiction Research Programs	001	1	9/15/2025	NEW	$0
														Subtotal = $465,669

Grand Total All Awards = $465,669

Top

All Categories

About

Search

Reports

Data Submission

Award Information

A mechanistic study of the role of the orexin system and insomnia within a buprenorphine opioid use disorder treatment sample

Award Number: R01DA061265

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/15/2025

PERIOD OF PERFORMANCE END DATE: 04/30/2030

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer