# Non-Invasive Vagal Nerve Stimulation in Patients with Opioid Use Disorders

> **NIH NIH UG3** · EMORY UNIVERSITY · 2021 · $13,728

## Abstract

Opioid addiction is a major crisis of epidemic proportions and drug overdose is now the leading cause of
accidental death in the United States. Treatment of Opioid Use Disorders (OUDs) includes medications with
effects on opioid receptors such as buprenorphine, but access is limited for many patients. Naltrexone is an
opioid antagonist that has been shown in recent studies to be equivalent in efficacy to buprenorphine. Initiation
of treatment with long-acting naltrexone, however, requires a period of abstinence of about seven days during
which time patients suffer from intense symptoms of withdrawal with a risk of relapse that can lead to
overdose-related death. Opioids have an inhibitory effect on norepinephrine and the sympathetic nervous
system, and many symptoms of withdrawal are driven by rebound activation of these systems. Dopaminergic
systems in brain areas including ventral striatum (nucleus accumbens) and medial prefrontal cortex (anterior
cingulate) play an important role in opioid addiction, craving and relapse, as do increases in inflammation. This
project will assess a form of neuromodulation involving non-invasive electrical stimulation of the vagus nerve
that may play a useful role during the period of opioid withdrawal before the initiation of long-term naltrexone
treatment in blocking norepinephrine, sympathetic, and inflammatory responses and enhancing peripheral
parasympathetic and central brain function in areas modulating drug craving (ventral striatum, anterior
cingulate). Our preliminary data on the effects of non-invasive Vagal Nerve Stimulation (nVNS) on stress
response in traumatized human subjects and patients with posttraumatic stress disorder (PTSD) show that
nVNS reliably blocks peripheral sympathetic and enhances parasympathetic function, reduces inflammatory
responses (interleukin-6, or IL-6), and enhances central brain responses (anterior cingulate) to stress. We now
propose to apply this technology to the treatment of patients with OUDs. Following verification using modelling
and determination of optimal dosing parameters, we will use these parameters to assess effects of nVNS
versus sham stimulation on opioid craving, peripheral autonomic, cardiovascular, inflammatory, and brain
functional responses measured with High-Resolution Positron Emission Tomography (HR-PET) and
radiolabeled water to videos of drug cues in recently treated patients with OUDs. Based on the outcome of this
research, we will proceed to the UH3 phase, which will involve a randomized, sham-controlled trial of nVNS in
patients with OUDs during the one to two week period of opioid withdrawal followed by assessment of craving,
HR-PET imaging of both brain function and brain dopaminergic function, and assessment of peripheral
autonomic, cardiovascular and inflammatory responses in conjunction with administration of nVNS or sham.
We hypothesize that nVNS will reduce opioid craving and inflammatory, peripheral autonomic and
cardiovascular response...

## Key facts

- **NIH application ID:** 10402169
- **Project number:** 3UG3DA048502-01A1S1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** James Douglas Bremner
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $13,728
- **Award type:** 3
- **Project period:** 2020-08-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10402169

## Citation

> US National Institutes of Health, RePORTER application 10402169, Non-Invasive Vagal Nerve Stimulation in Patients with Opioid Use Disorders (3UG3DA048502-01A1S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10402169. Licensed CC0.

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