Project Summary/Abstract Cocaine use disorder (CUD) continues to be a significant public health problem in the U.S. and more effective treatment strategies are needed. Repetitive transcranial magnetic stimulation (rTMS) is a non- invasive method of modulating specific brain regions that has shown preliminary efficacy in the treatment of CUD. However, sham-controlled clinical trials assessing cocaine consumption in CUD are lacking. Previous imaging studies in CUD have implicated broad regions of the prefrontal cortex, including the medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (dlPFC). Alterations in connectivity and cortical thickness have been shown to correlate with treatment response in CUD across different imaging modalities in each of these brain regions. Thus, our goal is to employ rTMS, using the H7-coil, since this coil can simultaneously and bilaterally stimulate the mPFC and dorsal ACC. Additionally, the H7-coil has been FDA-cleared for obsessive-compulsive disorder (OCD), based on its ability to reach these broad, deeper regions within the prefrontal cortex. As a result, treatment centers using the H7-coil are found across the United States (in 42 of 50 states), meaning that the use of this coil could move from the laboratory to the clinic relatively quickly. In this application, we first propose an outpatient double-blind sham-controlled trial (UG3 Phase) to investigate H7-coil feasibility, brain-behavior mechanism(s) using fMRI, and effect on initiation of abstinence from cocaine when administered prior to cognitive behavioral therapy (CBT). If the proposed go/no-go criteria are met, we will recruit a larger sample to evaluate the efficacy of combined rTMS/CBT for abstinence initiation in adults with CUD (UH3 Phase). If the UH3 data support therapeutic efficacy, this treatment could rapidly translate to the clinic given existing FDA-clearance for the H7-coil in psychiatric populations (i.e., OCD), and could become the first FDA-approved therapy for CUD.

Project Narrative Cocaine use disorder is prevalent in the U.S. and recent increases in the rate of cocaine-related deaths are concerning. Medications for cocaine use disorder have not shown consistent results and none have received FDA approval. Repetitive transcranial magnetic stimulation (rTMS) is an effective, FDA-cleared treatment option for patients with mental health disorders that have not responded to other treatments, including obsessive-compulsive disorder, and rTMS may be an effective strategy for cocaine use disorder.