# Use of a GLP-1 Agonist to Treat Opioid Use Disorder in Rats and Man

> **NIH NIH UG3** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2020 · $2,557,628

## Abstract

Project Summary. According to the Centers for Disease Control and Prevention, there were 70,237 drug
overdose deaths reported in the United States in 2017, more than 130 per day, with 67.8% involving opioids
[1]. While medications are available to treat the disease (e.g., methadone, suboxone, and extended release
naltrexone), relapse rates remain alarmingly high [2-4]. Clearly, new approaches are needed. To this end, we
recognize that addiction involves not only hijacking of the reward pathway, but also of the need pathway [5]. As
such, we posited that heroin seeking and taking should be reduced by peripheral stimulation of the glucagon-
like peptide-1 receptor (GLP-1R) ‘satiety’ pathway. In support, activation of the GLP-1R pathway has been
shown to inhibit not only ingestion of palatable sweets, water when thirsty, and salt when sodium deprived, but
also responding for alcohol, nicotine, and cocaine in rats and mice [6-12]. Here, we show for the first time that
pretreatment with a GLP-1R agonist also reduces heroin taking, seeking, and drug-induced reinstatement in
rats. The objective of this application is to test whether treatment with a GLP-1R agonist can reduce relapse in
humans with an opioid use disorder (OUD). One advantage of using GLP-1R agonists is that various
formulations already are approved for treatment of obesity and type 2 diabetes [13, 14]. UG3 Phase Aim G1
will conduct a randomized, double blind, placebo-controlled pilot study to determine whether once daily
treatment with the shorter acting GLP-1R agonist, liraglutide, can safely and effectively reduce craving and
brain responses to drug cues among patients in residential treatment for an OUD. UG3 Phase Aim G2 will use
well established animal models to test the efficacy and safety of a more risky, longer-acting, but more
efficacious, GLP-1R agonist, semaglutide, on heroin seeking and cue/drug/stress-induced reinstatement.
Milestones: (1) Demonstrate safety and efficacy liraglutide at approved doses to reduce craving and brain
responses to drug cues among patients in residential treatment for OUD who also are receiving counseling
only (CO) or counseling+buprenorphine/naltrexone (BUP/NA); (2) Verify that semaglutide is safe and effective
in reducing cue/drug/stress-induced heroin seeking in an animal model. If these milestones are met, UH3
Phase Aim H1 will conduct a two-arm, pseudo-randomized, placebo controlled multi-site clinical trial in
outpatients with an OUD to test whether treatment with semaglutide vs. placebo will reduce relapse out to 180
days in patients treated with CO and counseling+BUP/NA. UH3 Phase Aim H2 will use animal models to
further probe the efficacy and usefulness of semaglutide to prevent initiation of heroin self-administration, to
reduce ongoing heroin self-administration, or to serve as a non-opioid “bridge to care”, for example. If our
hypotheses are supported, we will show that treatment with GLP-1R agonists can safely and effectively reduce
opioi...

## Key facts

- **NIH application ID:** 10022118
- **Project number:** 5UG3DA050325-02
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** SCOTT C BUNCE
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,557,628
- **Award type:** 5
- **Project period:** 2019-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022118

## Citation

> US National Institutes of Health, RePORTER application 10022118, Use of a GLP-1 Agonist to Treat Opioid Use Disorder in Rats and Man (5UG3DA050325-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10022118. Licensed CC0.

---

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