# Deep Brain Stimulation (DBS) For Severe Treatment Refractory Methamphetamine Use Disorder

> **NIH NIH UG3** · UNIVERSITY OF COLORADO DENVER · 2022 · $721,027

## Abstract

Abstract:
Substance use disorders are prevalent, cause significant morbidity, and are a common cause of preventable
death. In contrast to alcohol and opioids, there are currently no FDA approved pharmacotherapies for
methamphetamine use disorder (MUD), despite extensive efforts at prior medication trials. Psychosocial
interventions are used to treat MUD, but many individuals remain refractory, highlighting the continued need for
novel treatment development. Our understanding of the neural basis of addiction has grown in recent decades,
underscoring the potential to selectively target addiction-related brain areas such as the nucleus accumbens
(NAc). Deep brain stimulation is commonly used to treat movement disorders, as well as obsessive compulsive
disorder, and allows chronic stimulation of subcortical brain structures, such as NAc. A growing body of animal
model and human clinical data suggests NAc stimulation may be beneficial in the treatment of addiction. Here
we propose a two-phase study, to test DBS of bilateral NAc for the treatment of MUD. Under the UG3 phase,
we will enroll a small number of subjects (n=5) with treatment-refractory MUD and will employ a subject- and
rater-blinded cross-over design using subjects as their own control. Subjects will receive inpatient detoxification,
followed by DBS surgery, then 1 month of residential substance use disorder treatment, and 12 weeks of
psychosocial interventions, along with 18 months of monitored DBS programming (subjects randomized to 6-
months-sham then 12-months-active stimulation vs. active-then-sham treatment). Our clinical outcomes are
methamphetamine use as measured by timeline followback and confirmed by urine drug screens, and self-
reported methamphetamine craving. We will also carefully assess safety and feasibility of the study procedures.
To investigate circuit-based target engagement, we will test for changes in activity during cue-craving and at rest
with longitudinal functional MRI (fMRI) and local field potential recording (pre-DBS programming, 6-, 12-, and
18-months post-surgery). The Medtronic Percept implantable pulse generator allows recording from the
implanted DBS leads, providing local field potential recording from the NAc itself during craving events
experienced in daily life and with cue-craving presentation in the clinic. If our pre-hoc safety, feasibility and
clinical and target engagement endpoints are achieved, we will proceed to the UH3 phase. In this phase, we will
conduct a randomized, subject- and rater-blinded, sham-controlled trial of DBS for methamphetamine use
disorder (n=20). Our design will be informed by UG3 findings (e.g., to determine expected time course for DBS
response) and will seek to test whether NAc DBS added to standard psychosocial interventions provides clinical
improvement in reducing methamphetamine use and craving above and beyond sham intervention. We will
further explore the underlying mechanisms associated with DBS treatment respon...

## Key facts

- **NIH application ID:** 10463210
- **Project number:** 1UG3DA054746-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** AVIVA ABOSCH
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $721,027
- **Award type:** 1
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463210

## Citation

> US National Institutes of Health, RePORTER application 10463210, Deep Brain Stimulation (DBS) For Severe Treatment Refractory Methamphetamine Use Disorder (1UG3DA054746-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10463210. Licensed CC0.

---

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