Cortical Stimulation of the Prefrontal Cortex With Transcranial Direct Current Stimulation Reduces Cue-Provoked Smoking Craving: A Randomized, Sham-Controlled Study

Felipe Fregni, M.D., Ph.D.; Paola Liguori, B.A.; Shirley Fecteau, Ph.D.; Michael A. Nitsche, M.D.; Alvaro Pascual-Leone, M.D., Ph.D.; and Paulo S. Boggio, Ph.D.

Objective: Because neuroimaging studies have shown that cue-provoked smoking craving is associated with changes in the activity of the bilateral dorsolateral prefrontal cortex (DLPFC), we aimed to investigate whether a powerful technique of noninvasive brain stimulation, transcranial direct current stimulation (tDCS), reduces cue-provoked smoking craving as indexed by a visual analog scale.

Method: We performed a randomized, sham-controlled crossover study in which 24 subjects received sham and active tDCS (anodal tDCS of the left and right DLPFC) in a randomized order. Craving was induced by cigarette manipulation and exposure to a smoking video. The study ran from January 2006 to October 2006.

Results: Smoking craving was significantly increased after exposure to smoking-craving cues (p < .0001). Stimulation of both left and right DLPFC with active, but not sham, tDCS reduced craving significantly when comparing craving at baseline and after stimulation, without (p = .007) and with (p = .005) smoking-craving cues. There were no significant mood changes in any of the conditions of stimulation. Adverse events were mild and distributed equally across all treatment conditions.

Conclusions: Our findings extend the results of a previous study on the use of brain stimulation to reduce craving, showing that cortical stimulation with tDCS is beneficial for reducing cue-provoked craving, and thus support the further exploration of this technique for smoking cessation.

(J Clin Psychiatry 2008;69:32-40; online ahead of print December 19, 2007)

Received Dec. 2, 2006; accepted April 12, 2007. From Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass. (Drs. Fregni, Fecteau, and Pascual-Leone); the Department of Clinical Neurophysiology, Georg-August University, Goettingen, Germany (Dr. Nitsche); and Mackenzie University, Sao Paulo, Brazil (Dr. Boggio and Ms. Liguori).

This work was supported by a grant from the Harvard Medical School Scholars in Clinical Science Program (NIH K30 HL04095) to Dr. Fregni. Ms. Liguori is supported by a research grant from Mackenzie University, Sao Paulo, Brazil (PIBIC-Mackenzie).

The authors thank Barbara Bonnetti, University of Sao Paulo, for administrative support. Ms. Bonnetti reports no financial affiliations or other relationships relevant to the subject of this article.

Dr. Pascual-Leone has received grant/research support from the National Institutes of Health. Drs. Fregni, Fecteau, Nitsche, and Boggio and Ms. Liguori report no financial affiliations or other relationships relevant to the subject of this article.

Corresponding author and reprints: Felipe Fregni, M.D., Ph.D., Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, 330 Brookline Ave. KS 452, Boston, MA 02215 (e-mail: ffregni@bidmc.harvard.edu).