Testing an accelerated transcranial magnetic stimulation protocol for methamphetamine use disorder — study protocol

Background Methamphetamine use disorder (MUD) is associated with increased mortality and high societal costs, yet no medication has shown consistent efficacy, and none are FDA-approved. Emerging evidence suggests that transcranial magnetic stimulation (TMS) targeting circuits implicated in cognitive control, incentive salience, craving and reward may offer therapeutic benefit. This study aims to evaluate the safety, feasibility, and preliminary efficacy of an accelerated intermittent theta-burst stimulation (iTBS) protocol applied to the left dorsolateral prefrontal cortex (DLPFC) for individuals with moderate to severe MUD. Methods This single-site, randomized, double-blind, sham-controlled (1:1 active: sham) pilot trial seeks to randomize 20 adults with moderate to severe MUD. Eligible participants are admitted to an inpatient research unit and receive up to 40 intermittent theta-burst stimulation (iTBS) or sham treatments over five days. After discharge, participants who receive at least one TMS treatment are followed weekly for 12 weeks. Primary outcomes are safety/tolerability and feasibility. Secondary outcomes include methamphetamine use (Timeline Follow-Back and weekly urine drug screens) and craving (Stimulant Craving Questionnaire-Brief and visual analog scale). Exploratory outcomes include pre- to post-treatment changes in MRI cue craving and MRI resting-state networks. Discussion If this pilot protocol proves safe and feasible, and provides preliminary evidence of efficacy, it would prompt future well-powered studies. This short-stay accelerated TMS protocol could provide a scalable model for neuromodulation in stimulant use disorder treatment, bridging the gap between residential and outpatient care. Trial registration ClinicalTrials.gov: NCT06320366. Registered 13 March 2024. https://clinicaltrials.gov/study/NCT06320366?term=NCT06320366 . Protocol version July 8, 2025.