# Portable hand-held proprietary xenon inhaler for rapid reduction of opioid withdrawal symptoms

> **NIH NIH R41** · NOBILIS THERAPEUTICS, INC. · 2021 · $319,992

## Abstract

Summary/Abstract
People with opioid use disorder (OUD) experience aversive opioid withdrawal symptoms (OWS) including
nausea, diarrhea, vomiting, and anxiety, which emerge when blood opioid levels wane. These symptoms
perpetuate unprescribed opioid use and accompanying morbidity and mortality, costing society nearly $80
billion per year. Withdrawal symptoms also emerge upon initiation of OUD pharmacotherapy with µ opioid
receptor antagonists (buprenorphine: partial; naltrexone: full), complicating, and sometimes resulting in patient
refusal of, treatment initiation or continuation. Better management of OWS is considered a “gateway to opioid
dependence treatment”. The a2-adrenergic receptor agonists clonidine and lofexidine attenuate opioid
withdrawal symptoms by inhibiting noradrenergic signaling. However, these agents have shortcomings: they
don’t fully suppress withdrawal symptoms or subjective discomfort, they induce problematic side effects
(hypotension, sedation, discontinuation syndrome), their dosing must be adjusted for renal or hepatic
impairment patients, and, as oral medications, they are slow acting. Thus, there is an urgent unmet need for
better and faster-acting treatments. One strategy to reduce OWS severity is to lower opioid-induced
inflammation and oxidative stress, which upregulate noradrenergic tone, sympathetic nervous system (SNS)
activity, and OWS severity. Inhaled xenon (Xe) gas inhibits inflammation and SNS activity and is hypothesized
to attenuate OWS severity. Xe is used at low concentration (28%) as an imaging agent and rarely induces
hypotension or dizziness, even in critical care populations. Xe rapidly (within minutes) equilibrates in brain and
other tissues and inhibits SNS activity, suggesting that it may be superior to a2-adrenergic agonists for
attenuating OWS. Moreover, Xe has no demonstrable abuse liability, making it superior to opioid agonist
substitution treatment for relieving OWS. In this Phase I STTR program, we propose to conduct preclinical
proof of concept studies in morphine-dependent mice to determine whether 30% Xe, which is non-sedating
when given by inhalation, rapidly reduces OWS severity. If Xe is effective, we will file an IND for a human
STTR Phase II study to evaluate whether Xe decreases OWS during medically-managed opioid tapering
required before buprenorphine initiation. Nobilis Therapeutics developed a proprietary portable hand-held Xe
inhalation device and the drug/device combination has been cleared by the US Food and Drug Administration
for testing in humans with Posttraumatic-Stress Disorder. This device also could be used in OUD studies,
supporting capital efficiency with exit potential. Nobilis holds a patent covering Xe’s anti-inflammatory effects
and licenses a patent from McLean Hospital covering Xe’s antianxiety effects. Accordingly, elements are in
place to develop and market Xe therapy, if effective, to several potential clients including care providers and
companies that sel...

## Key facts

- **NIH application ID:** 10390876
- **Project number:** 1R41DA055403-01
- **Recipient organization:** NOBILIS THERAPEUTICS, INC.
- **Principal Investigator:** Vlad Bogin
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $319,992
- **Award type:** 1
- **Project period:** 2021-09-30 → 2023-05-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10390876

## Citation

> US National Institutes of Health, RePORTER application 10390876, Portable hand-held proprietary xenon inhaler for rapid reduction of opioid withdrawal symptoms (1R41DA055403-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10390876. Licensed CC0.

---

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