rTMS plus cognitive-behavioral therapy for cocaine use disorder

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 6 days in the past 28 days;
5. Agree to no more than moderate alcohol consumption (\<15 drinks/week for men and \<8 drinks/week for women) and to avoid using amphetamine/methamphetamine and non-prescribed benzodiazepines or barbiturates; and
6. Women of childbearing potential must agree to use a method of contraception with proven efficacy and agree to not become pregnant during the study.

Exclusion Criteria:

1. Meets DSM-5 criteria for current moderate or severe major depressive disorder, OCD, bipolar disorder, schizophrenia, or any psychotic disorder (other than transient psychosis due to substance use);
2. Hamilton Depression Rating Scale score \> 17;
3. Young Mania Rating Scale score \>10;
4. Meets DSM-5 criteria for current moderate or severe other substance use disorder (aside from tobacco use disorder). Thus physiologic dependence on any substance other than nicotine is exclusionary (including alcohol);
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. Non-prescribed medications/drugs that in the opinion of the investigator may change the seizure threshold, including benzodiazepines, barbiturates, GHB/GBL, amphetamines/methamphetamine;
8. Any current DSM-5 psychiatric disorder(s) that meet the following criteria in the investigator's opinion 1) are unstable, 2) would be worsened by study procedures, or 3) are likely to require acute intervention 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 \<25);
16. Disqualifying response on the TMS Adult Safety Screen (TASS);
17. Implanted devices or stimulators (cardiac pacemakers, vagus nerve stimulators, spinal cord stimulators, cochlear implant, implanted brain stimulators)
18. Currently taking ototoxic medications (aminoglycosides, cisplatin);
19. Metal implants or paramagnetic objects in the body that prohibits MR scanning;
20. Claustrophobia that prohibits MR scanning; or
21. Legally mandated (e.g., to avoid incarceration or other penalties) to participate in SUD treatment program.
22. Moderate to severe heart disease