title: fMRI study of neural sensitization to hedonic stimuli in long-term, daily cannabis users.
abstract: Although there is emergent evidence illustrating neural sensitivity to cannabis cues in cannabis users, the specificity of this effect to cannabis cues as opposed to a generalized hyper-sensitivity to hedonic stimuli has not yet been directly tested. Using fMRI, we presented 53 daily, long-term cannabis users and 68 non-using controls visual and tactile cues for cannabis, a natural reward, and, a sensory-perceptual 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-users (cluster-threshold z = 2.3, P < 0.05). In the users, there were positive brain-behavior correlations between neural response to cannabis cues in fronto-striatal-temporal regions and subjective craving, marijuana-related problems, withdrawal symptoms, and levels of THC metabolites (cluster-threshold z = 2.3, P < 0.05). These findings demonstrate hyper-responsivity, and, specificity of brain response to cannabis cues in long-term 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-sectional 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. Hum Brain Mapp 37:3431-3443, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
authors.affiliation: Center for BrainHealth, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, Texas.
authors.forename: Francesca M
authors.initials: FM
authors.lastname: Filbey
authors.affiliation: Center for BrainHealth, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, Texas.
authors.forename: Joseph
authors.initials: J
authors.lastname: Dunlop
authors.affiliation: Center for BrainHealth, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, Texas.
authors.forename: Ariel
authors.initials: A
authors.lastname: Ketcherside
authors.affiliation: Center for BrainHealth, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, Texas.
authors.forename: Jessica
authors.initials: J
authors.lastname: Baine
authors.affiliation: Center for BrainHealth, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, Texas.
authors.forename: Tyler
authors.initials: T
authors.lastname: Rhinehardt
authors.affiliation: Center for BrainHealth, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, Texas.
authors.forename: Brittany
authors.initials: B
authors.lastname: Kuhn
authors.affiliation: Center for BrainHealth, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, Texas.
authors.forename: Sam
authors.initials: S
authors.lastname: DeWitt
authors.affiliation: Center for BrainHealth, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, Texas.
authors.forename: Talha
authors.initials: T
authors.lastname: Alvi
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D001931:Brain Mapping; D002188:Cannabis / Q000009:adverse effects*; D066249:Craving / Q000502:physiology; D003430:Cross-Sectional Studies; D003463:Cues; D005260:Female; D005518:Food Preferences / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D002189:Marijuana Abuse / Q000503:physiopathology* / Q000523:psychology; D009042:Motivation / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests; D012201:Reward; D013375:Substance Withdrawal Syndrome; D014796:Visual Perception / Q000502:physiology
keywords: addiction; cannabis use disorder; cue-elicited craving; fMRI; marijuana; mesocorticolimbic; reward