Project #3 In addicted individuals, exposure to conditioned drug cues (e.g., paraphernalia) elicits craving: the desire to use drugs1. Craving is increasingly recognized as an important contributory factor in addiction in general, and in cigarette smoking in particular2-7. Indeed, it has been shown to predict smoking and relapse following abstinence8-16, suggesting that treatments to mitigate the effects of cue-induced craving are needed17. Consistently, skills training in regulation of craving (a form of cognitive control) is an important feature of many interventions7, 18-22, including cognitive-behavioral therapy23, 24 and mindfulness-based treatments25, 26. Craving and its regulation have distinct neurobiological mechanisms. The neural correlates of craving include the ventral striatum and ventromedial prefrontal cortex27-29. We developed the Regulation of Craving (ROC) task30-35 to investigate the neural mechanisms associated with the regulation of craving. In this task, nicotine-dependent smokers are exposed to smoking-related stimuli. In one condition they experience craving, and in another (the regulation condition), they are instructed to use a strategy to modulate their craving for cigarettes31. Research has shown that self-reported craving and craving-related neural activity are significantly reduced during the regulation condition32, 34, 36. However, the exact neural mechanisms by which regulation operates depend on the strategy used. Specifically, regulation of craving with cognitive strategies depends on activation in prefrontal regions, typically associated with cognitive control, such as dorsolateral and ventrolateral prefrontal cortex32, 36-38. However, regulation with mindfulness strategies does not involve PFC34. We propose that brief training in regulation of craving may increase the efficacy of smoking cessation treatments, but that training in cognitive vs. mindfulness-based strategies may operate via different psychological and neural mechanisms. We propose to test the efficacy of such training by randomizing 126 cigarette smokers to the following conditions: 1) brief training in cognitive regulation of craving + standard treatment, 2) mindfulness-based training + standard treatment, and 3) standard treatment (no training). Training will be delivered in 4x1 hour computerized sessions over four weeks, with an 8-week follow-up. We will evaluate the effects of training on craving and regulation of craving measured by self-report and functional magnetic resonance imaging during the ROC task administered pre- and post- treatment, as well as smoking. This project promises to advance our psychological and neurobiological understanding of craving and its regulation, how these processes change during specific types of training, and how they relate to actual smoking behaviors. Results from this study hold potential to allow neurobiologically-targeted adaptation of current treatments, with an aim of discovering potentially precise biological predictions of treatment outcomes.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Specialized Center (P50)
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Special Emphasis Panel (ZDA1-EXL-T (03))
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Yale University
New Haven
United States
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Bold, Krysten W; Morean, Meghan E; Kong, Grace et al. (2017) Early age of e-cigarette use onset mediates the association between impulsivity and e-cigarette use frequency in youth. Drug Alcohol Depend 181:146-151
Zajac, Kristyn; Ginley, Meredith K; Chang, Rocio et al. (2017) Treatments for Internet gaming disorder and Internet addiction: A systematic review. Psychol Addict Behav 31:979-994
Morie, Kristen P; Yip, Sarah W; Zhai, Zu Wei et al. (2017) White-matter crossing-fiber microstructure in adolescents prenatally exposed to cocaine. Drug Alcohol Depend 174:23-29
Petry, Nancy M; Alessi, Sheila M; Olmstead, Todd A et al. (2017) Contingency management treatment for substance use disorders: How far has it come, and where does it need to go? Psychol Addict Behav 31:897-906
Carroll, Kathleen M; Kiluk, Brian D (2017) Cognitive behavioral interventions for alcohol and drug use disorders: Through the stage model and back again. Psychol Addict Behav 31:847-861
Yip, Sarah W; Morie, Kristen P; Xu, Jiansong et al. (2017) Shared microstructural features of behavioral and substance addictions revealed in areas of crossing fibers. Biol Psychiatry Cogn Neurosci Neuroimaging 2:188-195
Petry, Nancy M; Ginley, Meredith K; Rash, Carla J (2017) A systematic review of treatments for problem gambling. Psychol Addict Behav 31:951-961
Meredith, Steven E; Rash, Carla J; Petry, Nancy M (2017) Alcohol use disorders are associated with increased HIV risk behaviors in cocaine-dependent methadone patients. J Subst Abuse Treat 83:10-14
Zakiniaeiz, Yasmin; Cosgrove, Kelly P; Mazure, Carolyn M et al. (2017) Does Telescoping Exist in Male and Female Gamblers? Does It Matter? Front Psychol 8:1510
Kiluk, Brian D; DeVito, Elise E; Buck, Matthew B et al. (2017) Effect of computerized cognitive behavioral therapy on acquisition of coping skills among cocaine-dependent individuals enrolled in methadone maintenance. J Subst Abuse Treat 82:87-92

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