rTMS for Smoking Cessation

Cigarette smoking causes significant morbidity and mortality in the United States. Smoking
cessation is difficult, with the average smoker attempting to quit five times before
permanent success. Moreover, the majority of smoking quit attempts result in relapse. Brain
stimulation for smoke cessation is an exciting new area that builds on advancing neuroscience
knowledge concerning the functional neurocircuitry of addiction. Cortical stimulation can now
be performed non-invasively by transcranial magnetic stimulation (TMS). A few studies have
shown that TMS can reduce cue-elicited craving in smokers. Previous research by our group has
shown that a single session of 15 minutes high frequency (10 Hz) repetitive TMS (rTMS) at
100% motor threshold over the left dorsal lateral prefrontal cortex (an area that is likely
involved in inhibiting craving) can reduce cue-induced craving compared to sham TMS. However,
methodological concerns surrounding these preliminary findings limit definitive conclusions
about the effectiveness of TMS over a longer period of time. This R21 proposal will integrate
more rigorous experimental conditions, a true double-blind methodology, MRI guided
stimulation site and a longer-term follow-up assessment. Using rigorous double-masked methods
and MRI guided stimulation site, we propose that using active rTMS or sham rTMS, to determine
whether 10 sessions over a two week period consisting of 15 minute high frequency rTMS can
reduce cue-induced craving and cigarette consumption for cigarette smokers. The project will
also optimize rational rTMS parameters to make TMS to an efficacious treatment for nicotine
dependence. In the two years of project, we plan to recruit 42 treatment-seeking
nicotine-dependent cigarette smokers, both males and females of all ethnic and racial groups
between the ages of 18 and 60 to participate in the study. The 42 participants will be
randomly assigned to receive active prefrontal TMS or sham prefrontal TMS. The data from this
R21 will provide the information needed for launching a definitive larger-scale investigation
into potential clinical applications of TMS in smoke cessation. The results from this pilot
will also likely supply substantial information about the utility of cortical stimulation for
smoke cessation.

Inclusion Criteria:

1. Be between the ages of 18 and 60 years old.

2. Smoke 10 or more cigarettes per day and have a carbon monoxide (CO) level > 10 ppm
indicative of recent smoking.

3. Not received substance abuse treatment within the previous 30 days.

4. Meet criteria for nicotine dependence as determined by the FTND.

5. Be in stable mental and physical health.

6. If female, test non-pregnant and use adequate birth control.

7. No evidence of focal or diffuse brain lesion on MRI.

8. Be willing to provide informed consent.

9. Be able to comply with protocol requirements and likely to complete all study
procedures.

Exclusion Criteria:

1. Current dependence, defined by DSM-V criteria, on any psychoactive substances other
than nicotine or caffeine.

2. Contraindication to MRI (e.g., presence of metal in the skull, orbits or intracranial
cavity, claustrophobia).

3. Contraindication to rTMS (history of neurological disorder or seizure, increased
intracranial pressure, brain surgery, or head trauma with loss of consciousness for >
15 minutes, implanted electronic device, metal in the head, or pregnancy).

4. History of autoimmune, endocrine, viral, or vascular disorder affecting the brain.

5. History or MRI evidence of neurological disorder that would lead to local or diffuse
brain lesions or significant physical impairment.

6. Unstable cardiac disease, uncontrolled hypertension, severe renal or liver
insufficiency, or sleep apnea.

7. Life time history of major Axis I disorders such as: Bipolar Affective disorder
(BPAD), Schizophrenia, Post-traumatic Stress disorder (PTSD) or Dementia or Major
Depression.

8. Self report of >21 standard alcohol drinks per week in any week in the 30 days prior
to screening.

9. Other forms of nicotine delivery, such as nicotine patch, electronic cigarettes