# NOP Receptor Antagonist for OUD Pharmacotherapy

> **NIH NIH UG3** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $2,793,808

## Abstract

PROJECT SUMMARY
The opioid crisis has spawned a myriad of health consequences, including increased incidence of opioid use
disorder (OUD), a condition manifested by escalating physical and psychological impairments. Medication-
assisted treatment (MAT) aids in reducing mortality, opioid withdrawal, intake and opioid-seeking behaviors, thus
substantially improving the odds of successful recovery from OUD, particularly when coupled with psychosocial
interventions. Current opioid-based MAT (i.e., buprenorphine) is a leading adjunct in the proper management of
OUD patients, however there is a need to increase the armamentarium of therapeutics for OUD. The “non-
classical” nociceptin receptor (NOPr) binds the endogenous neuropeptide nociceptin/orphanin FQ (N/OFQ),
named for its efficacy to evoke nociception. Robust evidence supports the role of the N/OFQ-NOPr axis in the
rewarding effects of alcohol and the therapeutic potential of NOPr ligands in alcohol use disorder. While less is
established regarding this system in OUD, published literature implicates NOPr function in the regulation of the
rewarding and motivational effects of opioids. Building on the premise that brain N/OFQ-NOPr axis is involved
in OUD-related behaviors, we have partnered with BlackThorn Therapeutics to assess their novel and selective
NOPr antagonist BTRX-246040 as a potential OUD therapeutic. In this UG3, we will assess BTRX-246040 to
block oxycodone intake without abuse liability and to suppress oxycodone withdrawal and relapse-like behaviors
in male and female rats. We will also determine drug metabolism and pharmacokinetics interactions (DMPK)
between oxycodone and BTRX-246040 and brain penetrability in male and female rats. With achievement of the
UG3 milestones, we will conduct a Phase 1 clinical trial in non-treatment seeking OUD participants in the UH3.
Relative to placebo, we will ascertain the safety and tolerability of BTRX-246040 following oral oxycodone, the
DMPK profile of oral oxycodone following BTRX-246040, and efficacy to suppress opioid craving and drug-liking
in OUD participants. The second goal of the UH3 phase is to develop the preclinical data to support the prospect
that BTRX-246040 may serve as an adjuvant to buprenorphine MAT. These investigations with the NOPr
antagonist BTRX-246040 in the UG3/UH3 will advance the prospects to validate a novel medication for OUD.

## Key facts

- **NIH application ID:** 10085851
- **Project number:** 1UG3DA052282-01
- **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:** $2,793,808
- **Award type:** 1
- **Project period:** 2020-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10085851

## Citation

> US National Institutes of Health, RePORTER application 10085851, NOP Receptor Antagonist for OUD Pharmacotherapy (1UG3DA052282-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10085851. Licensed CC0.

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