Opioid use disorder (OUD) affects millions worldwide and remains the leading cause of fatal overdoses. Gold-standard medications such as buprenorphine reduce mortality and drug use, but relapse and treatment discontinuation rates remain high. The early months after treatment initiation carry particularly elevated risk for return to opioid use. These persistent challenges motivate adjunctive interventions that target drivers of craving and relapse.
Noninvasive brain stimulation, including transcranial magnetic stimulation (TMS), has been explored across substance use disorders (SUDs) to modulate cortical excitability and promote neuroplasticity. Patterned stimulation known as intermittent theta burst stimulation (iTBS) is designed to enhance synaptic potentiation and has demonstrated clinical utility in other indications cleared by regulatory authorities. Meta-analyses and reviews across SUDs report that TMS, including iTBS, can reduce craving and substance use, and it is hypothesized to act by engaging neural circuits that support drug-seeking and cue reactivity. Despite these findings, TMS research specifically in OUD is limited: few studies exist, many used single-session or accelerated designs, and only a minority included individuals on buprenorphine—the most commonly prescribed medication for OUD. The Vanderbilt Integrated Community TMS for Opioid Recovery (VICTORY) protocol aims to address these gaps by testing a repeated-session, clinically compatible iTBS schedule in buprenorphine-maintained patients and assessing neural circuitry changes when feasible.
VICTORY is a randomized, single-blind, sham-controlled clinical trial planning to enroll up to 120 individuals with OUD who are receiving buprenorphine. The study will be implemented at both an academic medical center and a private outpatient TMS clinic to evaluate feasibility and generalizability across care settings. The single-blind design blinds participants to active versus sham stimulation; study staff procedures for maintaining blinding are described in the full protocol.
Participants are adults with a diagnosis of opioid use disorder who are currently maintained on buprenorphine. Specific inclusion and exclusion criteria, screening procedures, and informed consent processes are detailed in the protocol. Recruitment occurs at the two study sites to capture a sample of individuals receiving routine buprenorphine care.
Active treatment consists of left dorsolateral prefrontal cortex (left DLPFC)–targeted iTBS. Each week participants receive two sessions of 1800 pulses each, administered once per week over an 8-week period for a total of 16 sessions. The comparator arm receives sham stimulation matched to the active schedule. The weekly schedule was chosen to align with routine clinical visits and improve feasibility for patients maintained on buprenorphine.
Primary clinical outcomes are change in craving, opioid use, and treatment retention. Assessments occur at baseline and at scheduled follow-up time points noted in the protocol (10 weeks, 12 weeks, and 20 weeks). Measures include validated craving assessments and substance use evaluation; specifics of instruments and urine toxicology schedules are reported in the protocol. The primary aim is to determine whether 16 sessions of active iTBS reduce craving and opioid use and increase retention relative to sham.
A subset of participants will be offered optional pre- and post-iTBS neuroimaging to probe neural mechanisms. The neuroimaging component aims to assess functional connectivity changes associated with treatment. A secondary aim tests whether reductions in craving correlate with changes in connectivity between the left DLPFC and the dorsal striatum and the anterior cingulate cortex (ACC).
The primary analysis will compare active and sham groups on craving, opioid use, and retention outcomes across follow-up visits. The neuroimaging substudy will examine associations between iTBS-related craving changes and functional connectivity alterations between left DLPFC and target subcortical and cingulate regions. Sample size, power calculations, and statistical models are specified in the full protocol. Where sample sizes are limited (for example, the neuroimaging subset), analyses are planned to be exploratory and hypothesis-generating.
The weekly iTBS schedule is intentionally aligned with routine care to enhance feasibility and participant adherence. Conducting the trial at both an academic center and a private outpatient TMS clinic is intended to test generalizability to different clinical settings. Ethical oversight, safety monitoring, and procedures for adverse event reporting are included in the protocol. The trial responds to prior limitations in OUD TMS research, such as small samples, exclusion of buprenorphine-treated patients, and inconsistent stimulation schedules.
This clinical trial is registered at ClinicalTrials.Gov (ID NCT07457489). Funding sources include a grant from the Tennessee Opioid Abatement Council and support from the National Institute on Drug Abuse (K23DA059690). The authors disclose that some investigators are employed by a commercial organization (Synaptic PSYCH); the protocol states that study design and reporting were developed independently of commercial influence. No study datasets were generated or analyzed at the time of the protocol publication. The protocol publication includes complete information on authorship, review, and editorial handling.
By testing a repeated weekly iTBS regimen targeted to the left DLPFC in people with OUD maintained on buprenorphine, VICTORY seeks to evaluate both clinical efficacy and underlying neural mechanisms in a pragmatic, real-world–oriented design. If active iTBS reduces craving, opioid use, or improves retention relative to sham, and if these changes track with functional connectivity alterations in frontostriatal and cingulate circuits, the findings would help justify larger trials and inform the integration of TMS into adjunctive care for OUD. The inclusion of multi-site implementation and neuroimaging aims to advance understanding of feasibility and mechanism in this high-risk patient population.