# Towards treatment for the complex patient: investigations of low-intensity focused ultrasound.

> **NIH NIH UG3** · INSTITUTE FOR CLINICAL RESEARCH, INC. · 2023 · $778,802

## Abstract

Opioid use disorder with co-morbid chronic pain and anxiety (OCpA) is a clinical triad associated with the
highest risk of opiate overdose deaths. Co-occurrence of these three disorders amplifies symptoms of each
and results in poorer treatment outcomes. There are shared neurobiological substrates for these disorders
such as reward processing and stress response. The anterior insula (AI) is a brain region involved in these
processes as well as in clinical disorder of pain, addiction, and anxiety. The AI is upregulated in pain, addiction
and anxiety disorders and is therefore a potential therapeutic target for neuromodulation. Low-intensity focused
ultrasound (LIFU) is a noninvasive method to inhibit cortical and deep brain regions. LIFU can reach deep
brain regions such as the AI with spatial specificity, unlike traditional noninvasive neuromodulation methods
which lack spatial specificity and depth penetration. LIFU can selectively target the insula and its subregions
and provides a potentially transformative method to reduce symptoms of pain, opiate craving, and anxiety in a
complex patient population such as OCpA. In the UG3 phase of this study, we will administer one session of
inhibitory LIFU to the AI in individuals with OCpA [opiate use disorder, chronic back pain, and anxiety disorders
(generalized anxiety disorder, post-traumatic stress disorder, or social anxiety disorder)]. The aim of this phase
of the study is to establish that LIFU vs sham LIFU to AI is safe and well tolerated as measured by adverse
events, clinical evaluation and repeated structural brain magnetic resonance imaging scans. We will also
gather preliminary data on the effect of LIFU to AI on opiate cue-induced craving and laboratory measures of
central sensitization(CS) which occurs with pain chronicity such as temporal summation of pain and
conditioned pain modulation. In the second phase of this project (UH3), we will examine the efficacy, in a larger
sample of individuals with OCpA, of repeated LIFU delivery on measures of pain and opiate cue-induced
craving, anxiety symptoms, interoception and autonomic reactivity as these outcomes are dysregulated in
OCpA and are mediated by the AI. LIFU will be delivered for 10 minutes each hour for 4 hours on a single day.
We hypothesize that repeated sessions of LIFU will reduce measures of CS, opiate cue-induced craving, state
anxiety symptoms, increase heart rate variability and normalize measures of interoception. We will examine
the durability and effect of 1 vs 2 sessions of repeated LIFU on these outcome measures. Repeated sessions
of other forms of neuromodulation result in increased magnitude and longer lasting effects. We hypothesize
that 2 sessions vs 1 of repeated LIFU will result in greater magnitude of change in the outcome measures.
Lastly, we will examine the safety and tolerability of repeated LIFU sessions. There is a need for improved
treatments for complex patients such as OCpA beyond combining treatments for...

## Key facts

- **NIH application ID:** 10775216
- **Project number:** 1UG3DA059407-01
- **Recipient organization:** INSTITUTE FOR CLINICAL RESEARCH, INC.
- **Principal Investigator:** MARY LEE
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $778,802
- **Award type:** 1
- **Project period:** 2023-09-30 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10775216

## Citation

> US National Institutes of Health, RePORTER application 10775216, Towards treatment for the complex patient: investigations of low-intensity focused ultrasound. (1UG3DA059407-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10775216. Licensed CC0.

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