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Using fMRI, we presented 53 daily, long\u2010term cannabis users and 68 non\u2010using controls visual and tactile cues for cannabis, a natural reward, and, a sensory\u2010perceptual control object to evaluate brain response to hedonic stimuli in cannabis users. The results showed an interaction between group and reward type such that the users had greater response during cannabis cues relative to natural reward cues (i.e., fruit) in the orbitofrontal cortex, striatum, anterior cingulate gyrus, and ventral tegmental area compared to non\u2010users (cluster\u2010threshold<jats:italic>z<\/jats:italic>\u2009=\u20092.3,<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). In the users, there were positive brain\u2010behavior correlations between neural response to cannabis cues in fronto\u2010striatal\u2010temporal regions and subjective craving, marijuana\u2010related problems, withdrawal symptoms, and levels of THC metabolites (cluster\u2010threshold<jats:italic>z<\/jats:italic>\u2009=\u20092.3,<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). These findings demonstrate hyper\u2010responsivity, and, specificity of brain response to cannabis cues in long\u2010term cannabis users that are above that of response to natural reward cues. These observations are concordant with incentive sensitization models suggesting sensitization of mesocorticolimbic regions and disruption of natural reward processes following drug use. Although the cross\u2010sectional nature of this study does not provide information on causality, the positive correlations between neural response and indicators of cannabis use (i.e., THC levels) suggest that alterations in the reward system are, in part, related to cannabis use.<jats:italic>Hum Brain Mapp 37:3431\u20133443, 2016<\/jats:italic>. \u00a9<jats:bold>2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.<\/jats:bold><\/jats:p>","DOI":"10.1002\/hbm.23250","type":"journal-article","created":{"date-parts":[[2016,5,11]],"date-time":"2016-05-11T12:42:25Z","timestamp":1462970545000},"page":"3431-3443","source":"Crossref","is-referenced-by-count":82,"title":["fMRI study of neural sensitization to hedonic stimuli in long\u2010term, daily cannabis users"],"prefix":"10.1002","volume":"37","author":[{"given":"Francesca M.","family":"Filbey","sequence":"first","affiliation":[{"name":"Center for BrainHealth, School of Behavioral and Brain Sciences University of 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