10 Days of Theta Burst Stimulation as a Tool to Treat Cocaine Dependence

Cocaine dependence is a particularly difficult substance use disorder to treat. There is
currently a lot of scientific inertia focused on the development of novel, neural circuit
based strategies for intervention. A prior NARC funded pilot project in non-treatment seeking
cocaine users demonstrated that a single session of medial prefrontal cortex theta burst
stimulation (MPFC cTBS) decreases baseline frontal-striatal activity in limbic regions and
decreases neural responses to cocaine uses. The effects of a single session however, erode
over the first few hours after treatment. Sustainable effects require multiple days of
treatment. GOAL: The next steps in pursuing this as a novel treatment are to 1) apply it to
treatment-engaged patients and 2) determine whether several sessions of cTBS will produce
sustainable and clinically-meaningful changes in cocaine use among these patients.

DESIGN: Treatment-engaged cocaine users and heavy alcohol users will be randomized to receive
10 sessions of real or sham LTD-like MPFC cTBS. This will be achieved by leveraging our
existing partnership with the MUSC Center for Drug and Alcohol Programs (CDAP) and the
Veterans Administration Substance Abuse Treatment Center Program (SATC) - which both provide
a 4 week intensive outpatient treatment program. MPFC cTBS will be given during weeks 2 and 3
of the program. Functional MRI data and clinical assessments will be acquired during weeks 1,
4, and at participant's 1 month and 2 month Accountability/Continuity visits. Hypothesis:
real cTBS treatment will enhance clinical outcomes (Aim 1 - including retention rates, number
of clean urine drug screens during CDAP treatment, relapse rates at 1 and 2 months) and will
produce a sustainable decrease in neural reactivity to cocaine cues (Aim 2 - week 1 versus
week 4, 1 month & 2 month follow ups).

Inclusion Criteria:

- Individuals from 21-65 years old currently enrolled in an intensive outpatient
treatment program.

Exclusion Criteria:

- Participants will be excluded if they are not between 21-65 years old, have current or
prior dependence (DSM-IV, because a DSM-V version of the SCID is not yet available) on
prescription or psychoactive drugs other than cocaine, alcohol, or nicotine but
including marijuana; past 6 month abuse of any prescription or psychoactive drugs
excluding cocaine, marijuana, alcohol or nicotine, lifetime history of head injury
with loss of consciousness, being pregnant or breast feeding, unstable medical illness
(e.g., hypertension, diabetes, myocardial infarction), presence of ferromagnetic metal
in their body, history of seizures. Additionally, to mitigate any potential risk of
seizures. As mentioned above, all participants will receive the Clinical Institute
Withdrawal Assessment of Alcohol (CIWAar) assessment before each TMS visit.
Individuals with a CIWA score >5 will be excused from the study. All individuals with
a history of medical detoxification or hospitalization for AUD (per the Assessments
listed above), self-reported alcohol withdrawal seizures, or delirium tremens will be
excluded from the study.