Pilot Study of Transcranial Magnetic Stimulation (TMS) in Nicotine Addiction

Primary objective: Transcranial magnetic stimulation (TMS) provides a non-invasive means of inhibiting brain neural activity. This pilot study will test whether 5 days of single pulse (sp) TMS reduces cue-induced nicotine craving and use in cigarette smokers. Hypothesis: We predict that active spTMS will significantly lower craving for nicotine compared with sham spTMS. Study population: Subjects will be up to 73 adult cigarette smokers (averaging greater than or equal to 10 cigarettes daily for greater than or equal to one year) with current nicotine dependence (based on DSM-IV criteria or Faerstrom Test for Nicotine Dependence score greater than or equal to 3). Subjects will not have other current major psychiatric disorders or substance abuse. Subjects in the pilot phase (one fMRI and one TMS session to valid brain mapping procedures) will be up to 25 healthy non-smokers. Design: Following a baseline day to evaluate subject characteristics, subjects will be randomly assigned to receive 5 days of active or sham spTMS session. spTMS at strength 120 percent of the motor threshold will be applied to the prefrontal cortex (PFC) using a figure-eight coil. Magnetic pulses will be triggered by cigarette-related pictorial cues and delivered at varying intervals prior to presentation of a cigarette-related picture. TMS pulses will not be delivered during emotionally salient images unrelated to nicotine or emotionally neutral images. Brain site localization will use a computerized navigation system based on functional and structural MRI scans obtained before the first session. Each session (lasting around 20 minutes) will consist of 108 trials (cue presentations): 72 with nicotine-associated cues and 18 each with non-drug-associated positive or neutral cues. Subjects return for follow-up fMRI and behavioral assessments one and two weeks after the final TMS session. Outcome measures: The primary outcome measure will be nicotine craving assessed with the Tobacco Craving Questionnaire and visual analog scales before and after every TMS session and at one- and two-week follow-up. Secondary outcome measures will include cigarette smoking over the test period and at follow-up assessed by self-report, salivary cotinine levels, and expired breath CO levels. A follow-up fMRI will evaluate changes in regional brain activity associated with changes in craving and TMS treatments. Benefits: Participants will not directly benefit from this study. This study may contribute to better scientific understanding of nicotine addiction and development of better treatment methods. Risks: The primary risks from TMS are transient headache, scalp discomfort, and hearing loss (minimized by wearing ear plugs). Seizures are very rare when spTMS is administered within accepted safety guidelines and individuals at increased risk of seizures are excluded. By excluding individuals with a history of non-drug-induced mania/ hypomania we minimize the risk of inducing a manic episode.