Deep Repetitive Transcranial Magnetic Stimulation for Alcohol Use Disorder

Phase 1: (up to 2 weeks), participants undergo a set of baseline assessments, including questionnaires, rating scales, and resting state functional magnetic resonance imaging (rsfMRI).

Phase 2, patients receive one of two treatments: High-frequency (10Hz, 100 trains of 3 sec with 15 sec inter train interval) dTMS targeting the ACC or sham stimulation for 30 min. Each treatment is preceded by provocation (pouring, holding and smelling the subject's favorite alcoholic beverage) designed to activate the relevant brain circuitry (provocation of symptoms may increase response rate to Deep TMS as was evident in the treatment of PTSD, cigarette smoking and OCD). dTMS sessions are conducted five times per week for 3 weeks, for a total of 15 sessions. A second scan that include rsfMRI and a risk-related decision-making task is conducted at the end of this phase.

Phase 3 includes 12 weeks of patients' follow-up, including clinical visits at weeks 1, 2, 4, 8 and 12 post treatment. During this phase, subjective and objective measures of alcohol use (self-report and analysis of urine samples for levels of ethyl glucuronide (EtG) and ethyl sulfate (EtS), respectively) are collected. Following completion of the main part by the individual, an "open label" treatment using the same parameters of the experiment is offer (regardless of treatment group).

Inclusion criteria

• Age 18 - 65
• Current diagnosis of alcohol dependence
• Alcohol use in the past month
• Right handed (self-report)
• If female, negative urine pregnancy test
• If female, must either agree to practice an effective birth control method; agree to abstinence from intercourse; be surgically sterile or postmenopausal for at least one year

Exclusion criteria

• Currently pregnant or breastfeeding
• More than mild cognitive impairment, as determined by a score on the Montreal cognitive assessment (MoCA) <25.
• Current diagnosis of schizophrenia, bipolar disorder, or other psychotic disorder
• Use in the past 2 weeks of medication or illicit drug with known high pro-convulsant action, as self-reported, or detected using urine toxicology screening; and with accordance to the Physician best Judgment.
• Any history of clinically significant neurological disorders, including organic brain disease, epilepsy, stroke, brain lesions, multiple sclerosis, previous neurosurgery or personal history of head trauma that resulted in loss of consciousness for > 5 minutes and retrograde amnesia for > 30 minutes (self-reported history).
• Any history of seizures other than febrile childhood seizures (self-reported history)
• Clinically significant hearing impairment
• Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head (pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips, metallic prostheses, permanent eyeliner, implanted delivery pump, or shrapnel fragments) or fear of enclosed spaces). Eligibility will be determined by the "MRI Safety Screening Questionnaire" and verified, if necessary, by a radiology consultant. Some of the patients that will be excluded from the imaging part of the study will be included in the clinical part.
• Any psychiatric, medical or social condition whether or not listed above, due to which, in the judgment of the investigators and after any consults if indicated, participation in the study is not in the best interest of the patient.