# Targeting the Ghrelin System for Novel Opioid Use Disorder Therapeutics

> **NIH NIH UG3** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $237,381

## Abstract

PROJECT SUMMARY
The coronavirus disease 2019 (Covid-19) pandemic erupted into the midst of the drug overdose crisis in the US.
Over 60% of drug overdoses are linked to opioid analgesics, with repeated overdoses indicative of the
development of opioid use disorder (OUD), a growing and life-threatening medical condition. Given that we are
unable to decouple opioid-induced pain relief from opioid abuse and OUD at present, opioid analgesics will
remain essential in medicine and their use is likely to co-occur with Covid-19 illness. Opioid medications generally
enhance viral replication, pathogenesis, and infectious disease progression, in part via weakening the immune
system. The SARS-CoV-1 virus is neuroinvasive and neurovirulent and is linked to progressive central nervous
system (CNS) symptoms (e.g., confusion, delirium, dysphoria), aligning with symptomatology seen in some
Covid-19 patients. As for other viruses, SARS-CoV-2 immunopathology and disease progression will prove to
be a function of virus pathogenesis and host vulnerability, one of which may be chronic opioid use in pain
management and/or OUD. These findings inspire the urgent need to understand how opioids impact specific
host vulnerability factors and cofactors, and how medications proposed to treat Covid-19 affect opioid signaling,
particularly within single cells that control CNS actions of opioids. Initial observations suggest that host factors
involved in SARS-CoV-2 cellular entry are altered in the brains of heroin users. We recently reported that brain-
region specific expression of immune cytokines and chemokines tracks with lifetime fentanyl intake in rats,
suggesting that opioid exposure regulates host viral entry and immune function relevant to Covid-19 infection.
Given the concurrent Covid-19 and overdose crises, the chronic use of opioids in pain management, the growing
problem of OUD as well as illegal abuse of opioid drugs, we propose two specific aims of immediate relevance
to predicting Covid-19 disease severity and appropriate therapeutics in opioid-exposed OUD patients. Based
upon this premise, we will test the hypothesis that withdrawal from chronic fentanyl self-administration in male
and female rats will impact key targets that mediate SARS-CoV-2 infection in identified single cells in CNS via
single-nuclei RNAseq transcriptomics (Aim 1) and that acute or chronic Covid-19 medication candidates will
alter signaling profiles of opioids (e.g., fentanyl, buprenorphine) in a cellular system (Aim 2). We expect to
discover altered markers of host viral entry and immunological status in identified single CNS cells following
chronic fentanyl self-administration, establishing the potential for enhanced neurological damage in Covid-19
patients. We also expect to demonstrate interactions between Covid-19 medications and opioid signaling which
predict potential interactions in vivo. These innovative aims are consistent with the goals of NOT-DA-20-047 to
determine if opioid exp...

## Key facts

- **NIH application ID:** 10168769
- **Project number:** 3UG3DA050317-01S1
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Kathryn A. Cunningham
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $237,381
- **Award type:** 3
- **Project period:** 2019-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168769

## Citation

> US National Institutes of Health, RePORTER application 10168769, Targeting the Ghrelin System for Novel Opioid Use Disorder Therapeutics (3UG3DA050317-01S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10168769. Licensed CC0.

---

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