Introduction: Cue reactivity is defined as an observable, classically conditioned response to drugs. Chronic cocaine use is associated with enhanced cue reactivity. Our aims were: (1) to evaluate reactivity to cocaine and neutral picture cues in non-treatment seeking chronic cocaine smokers who were abstinent from cocaine use for 72 hours and control participants using functional magnetic resonance imaging (fMRI), and (2) to assess whether cue reactivity related brain areas were correlated with subjective craving ratings. Method: fMRI data were collected from non-treatment seeking cocaine-smokers (29-53 yrs.; 15M; 5F) who were abstinent from cocaine smoking for 72 hours, and control participants (25-53 yrs.; 13M; 4F) using a Siemens 3T magnet while they took part in a cue viewing task that included cocaine and neutral cues. Participants also provided craving ratings while they viewed the cues. Results: Contrasting activation of cocaine smokers to that of controls revealed significantly greater activation in response to cocaine cues in the following brain areas: anterior cingulate gyrus, posterior cingulate gyrus, left insula, right amygdala, left precuneous, and bilateral orbitofrontal cortex, caudate, Para hippocampal gyrus, thalamus, frontal pole, and lingual gyrus. In contrast, when comparing cocaine smokers to controls no significant difference in activation to neutral cues was observed. Increased cue reactivity was not positively correlated with cocaine users’ subjective craving ratings. Conclusion: Enhanced cue reactivity reflects cocaine users’ increased salience to cocaine cues, and this enhancement may not indicate increased craving for the drug. Results have implications for treatment development. Future studies will examine how these cue reactivity related brain areas are causally related during viewing cocaine cues in cocaine users.
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