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AbstractDeep brain stimulation (DBS) is an established method for the treatment of disabling motor symptoms in patients with Parkinson’s disease, dystonia or essential tremor. The reversibility of DBS enables its application also in brain regions supposed to be involved in cognitive processes. There is evidence that malfunction of the brain’s reward system is a crucial step for the development and maintenance of addictive behavior. Neuromodulation of this network using DBS might significantly improve the poor prognosis of addictive patients relapsing after standard therapy. Motivated by an accidental observation we used the nucleus accumbens (NAc)/ventral striatum (VS), which has a central position in the dopaminergic reward system as target for the off-label use of DBS in 5 alcohol addictive patients. The patients responded to bilateral, chronic, high-frequency DBS (average follow-up: 50 months) with significant and ongoing improvement of craving. Two patients remained completely abstinent longer than four years. Electrical stimulation was tolerated without permanent side effects. According to preliminary data from electrophysiological recordings when patients performed neuropsychological tasks neuromodulation of the NAc/VS probably counterbalances the effect of drug related stimuli triggering in addictive patients involuntarily drug-seeking behavior. Momentarily prospective randomized studies are recruiting patients for NAc-DBS to treat either opoid addiction (Cologne, Germany) or severe alcohol addiction ((i) Guodong Gao, China; (ii) Magdeburg, Germany, (iii) multicentric study, Germany (participating centers: Magdeburg, Cologne, Heidelberg/Mannheim), or to prevent opiate relapses (Guodong Gao, China).