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.

Early Cannabis Use and Neurocognitive Risk: A Prospective Functional Neuroimaging Study

“…A significant dose-response relationship was found in cuneus activity at follow-up, where greater deactivation was associated with greater cannabis use. These results are consistent with work demonstrating differential cuneus activation between abstinent adolescent marijuana users and control subjects (11) and adult daily marijuana users and control subjects (33). Furthermore, a recent pharmacological fMRI study showed that cuneus activity is modulated by THC administration (34).…”

Orbitofrontal cortex connectivity as a mechanism of adolescent behavior change

“…For example, recent studies reflect that the OFC may underlie neural sensitivity to cannabis cues 65 and place individuals at greater risk for a more protracted trajectory of use, particularly when youth begin using at an earlier age 66 . Further, OFC dysregulation appears to be a signature feature across anxiety, OCD, and anorexia nervosa 67–69 , subsequently indicating its relevance as a marker of neural health, and potentially, a region that may be disrupted during the transition into emergent or more long-standing psychiatric conditions.…”

The cannabis withdrawal syndrome: current insights

“…If compared with nonusers, long-term cannabis users were demonstrated to have greater brain activity during cannabis cues relative to natural reward cues (ie, fruit itself being superior to neutral cues) in the orbitofrontal cortex, striatum, anterior cingulate gyrus, and ventral tegmental area 72. The users had positive correlations between neural response to cannabis cues in the fronto-striatal-temporal regions and subjective craving, cannabis-related problems, serum levels of THC metabolites, and the intensity of CWS.…”

“…The users had positive correlations between neural response to cannabis cues in the fronto-striatal-temporal regions and subjective craving, cannabis-related problems, serum levels of THC metabolites, and the intensity of CWS. All of which were not found in non-cannabis users,72 suggesting a sensitization and specificity of the brain response to cannabis cues in long-term cannabis users 72…”