Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023;10(1):1117.
Epub 2023 Aug 2.

Noninvasive Vagal Nerve Stimulation for Opioid Use Disorder

J Douglas Bremner  1   2   3 , Asim H Gazi  4 , Tamara P Lambert  5 , Afra Nawar  4 , Anna B Harrison  4 , Justine W Welsh  1 , Viola Vaccarino  6   7 , Kevin M Walton  8 , Nora Jaquemet  1 , Kellen Mermin-Bunnell  1 , Hewitt Mesfin  1 , Trinity A Gray  1 , Keyatta Ross  1 , Georgia Saks  5 , Nikolina Tomic  4 , Danner Affadzi  1 , Marom Bikson  9 , Amit J Shah  3   6   7 , Kelly E Dunn  10 , Nicholas A Giordano  11 , Omer T Inan  4   5
Affiliations

Noninvasive Vagal Nerve Stimulation for Opioid Use Disorder

J Douglas Bremner et al. Ann Depress Anxiety. 2023.

Abstract

Background: Opioid Use Disorder (OUD) is an escalating public health problem with over 100,000 drug overdose-related deaths last year most of them related to opioid overdose, yet treatment options remain limited. Non-invasive Vagal Nerve Stimulation (nVNS) can be delivered via the ear or the neck and is a non-medication alternative to treatment of opioid withdrawal and OUD with potentially widespread applications.

Methods: This paper reviews the neurobiology of opioid withdrawal and OUD and the emerging literature of nVNS for the application of OUD. Literature databases for Pubmed, Psychinfo, and Medline were queried for these topics for 1982-present.

Results: Opioid withdrawal in the context of OUD is associated with activation of peripheral sympathetic and inflammatory systems as well as alterations in central brain regions including anterior cingulate, basal ganglia, and amygdala. NVNS has the potential to reduce sympathetic and inflammatory activation and counter the effects of opioid withdrawal in initial pilot studies. Preliminary studies show that it is potentially effective at acting through sympathetic pathways to reduce the effects of opioid withdrawal, in addition to reducing pain and distress.

Conclusions: NVNS shows promise as a non-medication approach to OUD, both in terms of its known effect on neurobiology as well as pilot data showing a reduction in withdrawal symptoms as well as physiological manifestations of opioid withdrawal.

PubMed Disclaimer

Figures

Figure 1:
Figure 1:
Neural circuits in Opioid Use Disorder (OUD) and Post-traumatic Stress Disorder (PTSD) and effects of Non-invasive Vagal Nerve Stimulation (nVNS). OUD and PTSD share overlapping brain circuits (hence the association of trauma with OUD) including Orbitofrontal Cortex (OFC), thalamus and hippocampus (red colored regions in diagram) as well as areas also impacted by nVNS like Prefrontal Cortex (PFC), Anterior Cingulate Cortex (ACC), insula and amygdala. nVNS additionally has effects on Somatosensory Cortex (SC).
Figure 2:
Figure 2:
Study protocol for Transcutaneous Cervical Vagus Nerve Stimulation (tcVNS) in Opioid Use Disorder (OUD). Patients with OUD discontinued use of opioids by midnight of the night before the protocol. They presented early in the morning before initiation of Medication for Opioid Use Disorder (MOUD) initiation and underwent measurement of physiological variables with wearable sending devices (heart rate, respiratory variability) and behavioral variables with rating scales (withdrawal, pain, distress). tcVNS or sham was paired with opioid use cues (videos) in a double blind randomized fashion. There were significant increases in behavioral and physiological measures of withdrawal in the sham versus tcVNS group (i.e. tcVNS blocked measures of opioid withdrawal both subjective and objective related to sympathetic nervous system function).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Buchanich JM, Balmert LC, Williams KE, Burke DS. The effect of incomplete death certificates on estimates of unintentional opioid-related overdose deaths in the United States, 1999–2015. Public Health Rep. 2018; 133: 423–31. - PMC - PubMed
    1. Centers for Disease Control and Prevention. Drug Overdose Death Data https://www.cdc.gov/drugoverdose/data/statedeaths.html. Centers for Disease Control and Prevention. p. 2018; 2017; [cited Jul 9 2018]. Available from: https://www.cdc.gov/drugoverdose/data/statedeaths.html.
    1. CDC. Drug overdose deaths in the U.S. Top 100,000 annually. In: CDC, editor. Atlanta: Centers for Disease Control; 2021.
    1. Bailey GL, Herman DS, Stein MD. Perceived relapse risk and desire for medication assisted treatment among persons seeking inpatient opiate detoxification. J Subst Abuse Treat. 2013; 45: 302–5. - PMC - PubMed
    1. Sigmon SC, Bisaga A, Nunes EV, O’Connor PG, Kosten T, et al. Opioid detoxification and naltrexone induction strategies: recommendations for clinical practice. Am J Drug Alcohol Abuse. 2012; 38: 187–99. - PMC - PubMed

LinkOut - more resources