rTMS and Cognitive-behavioral Therapy for Cocaine Use Disorder

The goal of the study is to investigate the feasibility, safety, and effect of rTMS on mPFC/dACC activity using a combination of fMRI and clinical outcome measures, when used as an augmentation to CBT. Our hypothesis is that we will meet the following milestones prior to moving forward to the UH3 phase (a clinical trial for CUD). * Feasibility: At least 75% of participants will receive at least 15 out of 20 rTMS sessions with no participants experiencing a study-related serious adverse event * Mechanism: Compared to baseline, after 1 week of rTMS, participants who received active rTMS will demonstrate a 15% decrease in RSFC (resting state functional connectivity) between the DLPFC (dorsolateral prefrontal cortex) and anterior cingulate * Efficacy: During the final 12 weeks of the trial (weeks 2-13), at least 15% of participants who received active rTMS will demonstrate 3 consecutive weeks of abstinence Participants will: * Have two brain MRI scans; * Undergo 1 week of daily rTMS (or sham) treatments (up to 20 sessions), and; * Have 12 weeks of once-weekly cognitive-behavioral therapy for the treatment of cocaine use disorder. Researchers will compare active (real) rTMS to sham (placebo) rTMS. All participants will receive cognitive-behavioral therapy. The former principle investigator, Dr. Derek Blevins, has vacated his position (February 2025), and has transferred the principle investigator role to Dr. John Mariani, the STARS Clinic Director.

Inclusion Criteria: 1. Age 22-65; 2. Able to give informed consent and comply with study procedures; 3. Meets DSM-5 criteria for current moderate/severe CUD and are treatment-seeking; 4. Used cocaine at least 9 days in the past 28 days, with at least weekly cocaine use; 5. Agree to no more than moderate alcohol consumption (\10; 4. Meets DSM-5 criteria for current moderate/severe other substance use disorder (aside from tobacco use disorder; physiologic dependence on any other substance other than nicotine, including alcohol, is exclusionary); 5. Heavy weekly alcohol drinking as defined by an average of \>14 drinks/week for men or \>7 drinks/week for women on average during the past 28 days; 6. Prior alcohol, benzodiazepine, or barbiturate withdrawal that resulted in hospitalization, medical detoxification, or resulted in seizures or delirium tremens; 7. More than twice weekly use of non-prescribed medications/drugs that may change the seizure threshold, including benzodiazepines, barbiturates, GHB/GBL, amphetamines/methamphetamine; 8. Any other current DSM-5 psychiatric disorder(s) that in the investigator's judgment are unstable, would be disrupted by study procedures, or are likely to require pharmacotherapy or psychotherapy during the study period; 9. Significant current risk of suicide, indicated by either: (1) "yes" response on #3, #4, or #5 on the C-SSRS and a psychiatric risk assessment indicating a moderate or high risk of suicide or (2) suicidal behavior in the past year that, in the opinion of the clinician, increases risk of future suicidal behavior over the study period (note: non-suicidal self-injurious behavior is not exclusionary). 10. Females with a positive urine pregnancy test and/or breast feeding 11. Clinically significant abnormal cardiac functioning per electrocardiogram (ECG) (required for any participant age 60 years and older); 12. Seizure history including: seizure disorder/epilepsy, alcohol/drug withdrawal seizure, or seizure deemed by the study physician to be related to cocaine intoxication/withdrawal (note: febrile seizures are not exclusionary) 13. Other conditions associated with seizure: epilepsy and the following acute or subacute neurologic disorders: stroke (ischemic or hemorrhagic), multiple sclerosis, traumatic brain injury (moderate or severe), neurosurgery, meningoencephalitis, increased intracerebral pressure, or intracerebral abscess, neurodegenerative disorders, and parenchymal or leptomeningeal brain tumors (per the TMS core guidelines which is attached). Participants with a history of metabolic abnormalities (hyponatremia, hypocalcemia, hypomagnesemia, hypo or hyperglycemia, renal failure/uremia, liver failure), recent infection with fever, and serious alcohol withdrawal will be assessed by the MD/NP to ensure these conditions have resolved and are not currently present (per the TMS core guidelines which is attached). In this protocol, we will also exclude glaucoma, severe migraine (particularly complicated migraines with significant aura and hemiparesis, and severe vertebrobasilar migraines, that may lead to brainstem infarctions). 14. Medications that lower seizure threshold and in the opinion of the investigator impose significant seizure risk for the individual (including tricyclic antidepressants, monoamine oxidase inhibitors, bupropion, clozapine, and anticholinergics). The use of lithium, antipsychotics (other than clozapine), antibiotics, antihistamines, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors will be carefully assessed by the physician 15. Cognitive disorder (MMSE \