The Effects of Theta Burst Stimulation on the Brain Response to Drug and Alcohol Cues

High relapse rates among substance dependent individuals are likely due to a combination of factors that involve limbic circuits in the brain involved in craving, including vulnerability to salient cues. Emerging data suggests that non-invasive, targeted brain stimulation may be able to modulate activity in these circuits and decrease craving. The primary goal of this pilot study is to determine the extent to which a single session of continuous theta burst stimulation to the medial prefrontal cortex can attenuate limbic circuitry involved in craving among cocaine users and alcohol users. This will be tested through a double-blind,sham-controlled brain stimulation and brain imaging study in a cohort of polysubstance abusers and alcohol users.

This parent protocol contains two components - one of which is targeting cocaine users, the other of which is targeting heavy alcohol users (who will also serve as an appropriate control group for the cocaine users - who typically have comorbid alcohol use disorders). All participants will receive one session of real and one session of sham (randomized) continuous theta burst stimulation (TBS).TBS is a form of non-invasive transcranial magnetic stimulation (TMS).Continuous TBS is designed to lower cortical excitability, and requires a shorter stimulation period than typical low frequency TMS. The investigators will test the hypotheses that stimulation over the medial prefrontal cortex will attenuate activity in the medial prefrontal cortex (Aim 1), using single pulse TMS in the magnetic resonance imaging scanner. Through this innovative technique it is possible to apply a single pulse of TMS to the medial prefrontal cortex and model the hemodynamic response at the stimulation site as well as monosynaptic target regions, including the striatum. The investigators will also investigate the effect of TBS on neural response to drug cues (Aim 2). The results of these aims will be further correlated with self-reported assessments of craving throughout each experimental visit. These data will be preliminary data for a subsequent R01 focused on the sustained effects of multiple sessions of TBS and their efficacy in lowering craving for extended periods of time in treatment-seekers.

Eligibility Criteria:
Inclusion Criteria:

* Age 25-55
* Non-treatment seeking cocaine users (with or without comorbid alcohol use disorder)
* Current alcohol use greater than 20 standard drinks per week
* Current DSM-V Alcohol Use Disorder diagnosis, including the loss of control item
* Currently not engaged in, and do not want treatment for, alcohol related problems
* Able to read and understand questionnaires and informed consent
* Lives within 50 miles of the study site

Exclusion Criteria \[These are listed in greater detail in the CIA Core\]:

* Any current DSM-V Axis I diagnosis except Alcohol, Cocaine, or Nicotine Use Disorder
* Current or past substance dependence criteria other than cocaine, marijuana, or alcohol, smoking \>1 pack of cigarettes per day
* Current use of any psychoactive substance except cocaine, nicotine, and marijuana or medications as evidenced by self-report or urine drug screen
* Current breath alcohol concentration \>0.002
* Positive urine drug screen for stimulants (including cocaine, amphetamine, methamphetamine, etc.) at the Scanning/Stimulation visits and signs of alcohol withdrawal. Based on the sensitivity of this test, this will require that the participants abstain from cocaine use for 48 hours prior to the intervention
* History of seizures or migraine headaches
* History of head trauma or epilepsy
* Violation of other magnetic resonance imaging safety measures
* Current suicidal or homicidal ideation
* Presence of ferrous metal in the body, as evidenced by metal screening and self-report
* Severe claustrophobia or extreme obesity that preclude placement in the MRI scanner
* For female participants, pregnancy, as evidenced by a urine pregnancy test administered on the day of the scanning session