BACKGROUND: The core clinical symptoms of addiction include an enhanced incentive for drug taking (craving), impaired self-control (impulsivity and compulsivity), emotional dysregulation (negative mood) and increased stress reactivity. Symptoms related to impaired self-control involve reduced activity in anterior cingulate cortex (ACC), adjacent prefrontal cortex (mPFC) and other brain areas. Behavioral training such as mindfulness meditation can increase the function of control networks including those leading to improved emotion regulation and thus may be a promising approach for the treatment of addiction. METHODS: In a series of randomized controlled trials (RCTs), we tested whether increased ACC/mPFC activity is related to better self-control abilities in executive functions, emotion regulation and stress response in healthy and addicted populations. After a brief mindfulness training (Integrative Body-Mind Training, IBMT), we used the Positive and Negative Affect Schedule (PANAS) and Profile of Mood States (POMS) to measure emotion regulation, salivary cortisol for the stress response and fMRI for brain functional and DTI structural changes. Relaxation training was used to serve as an active control. RESULTS: In both smokers and nonsmokers, improved self-control abilities in emotion regulation and stress reduction were found after training and these changes were related to increased ACC/mPFC activity following training. Compared with nonsmokers, smokers showed reduced ACC/mPFC activity in the self-control network before training, and these deficits were ameliorated after training. CONCLUSIONS: These results indicate that promoting emotion regulation and improving ACC/mPFC brain activity can help for addiction prevention and treatment.