Developing rTMS Treatment Strategies for Pain in Opiate Dependence

Chronic use of opiates is a rapidly escalating crisis in the United States, with over 4.3
million Americans dependent on opiate analgesic, an escalating rate of opiate overdose
deaths, and a resurgence of intravenous heroin use leading to total societal cost exceeding
$55 billion. The struggle to break the addiction cycle is likely due to factors that affect
neural circuits that govern craving and cognitive control. There is growing interest in the
utilization of prefrontal cortex repetitive transcranial magnetic stimulation (rTMS) as a
novel, non-invasive, non-pharmacologic approach to decreasing craving among chronic opiate
users. At this early stage of development, however, it is unclear if the best TMS strategy is
to (Strategy 1, Aim 1) increase activity in the dorsolateral prefrontal cortex, or (Strategy
2, Aim 2) decrease activity in the ventromedial prefrontal cortex.

DESIGN: To parametrically evaluate these two promising treatment strategies, the
investigators have developed a design where opiate dependent individuals and healthy controls
will be randomized to receive either one placebo-like TMS treatment, or one of two real TMS
treatments (DLPFC iTBS or MPFC cTBS). Participants with opiate dependence will be recruited
from the local community, as well as the MUSC Center for Drug and Alcohol Programs (CDAP),
the Ralph H. Johnson Substance Abuse Treatment Center and local pain clinics. Healthy
controls will be recruited from the local community. Approved Study Team Members will visit
the above mentioned clinics and community and talk with patients. Individuals who consent
will receive interleaved TMS/BOLD imaging and our established MRI-based thermal pain paradigm
immediately before and after rTMS. The investigators will also measure subjective pain and
opiate craving ratings. The relative efficacy of Strategy 1 vs 2 will directly translate to
development of a large clinical trial of rTMS as an innovative, new treatment option for pain
in opiate dependent individuals.

Inclusion Criteria:

1. Able to read and understand questionnaires and informed consent.

2. Able to read and understand questionnaires and informed consent.

3. Lives within 50 miles of the study site.

4. Is not at elevated risk of seizure (i.e., does not have a history of seizures, is not
currently prescribed medications known to lower seizure threshold)

5. Does not have metal objects in the head/neck.

6. Does not have a history of traumatic brain injury, including a head injury that
resulted in hospitalization, loss of consciousness for more than 10 minutes, or having
ever been informed that they have an epidural, subdural, or subarachnoid hemorrhage.

7. Does not have a history of claustrophobia leading to significant clinical anxiety
symptoms.

Exclusion Criteria:

1. Any psychoactive illicit substance use (except marijuana and nicotine) within the last
30 days by self-report and urine drug screen. For marijuana, no use within the last
seven days by verbal report and negative (or decreasing) urine THC levels.

2. Meets DSM IV criteria for current axis I disorders of major depression, panic
disorder, obsessive-compulsive disorder, post traumatic stress syndrome, bipolar
affective disorder, schizophrenia, dissociate disorders, eating disorders, and any
other psychotic disorder or organic mental disorder.

3. Has current suicidal ideation or homicidal ideation.

4. Has the need for maintenance or acute treatment with any psychoactive medication
including anti-seizure medications and medications for ADHD.

5. Females of childbearing potential who are pregnant (by urine HCG), nursing, or who are
not using a reliable form of birth control.

6. Has current charges pending for a violent crime (not including DUI related offenses).

7. Does not have a stable living situation.

8. Suffers from chronic migraines.