Childhood adversity negatively influences all stages of the addiction process and is associated with persistent alterations in neuroendocrine, autonomic and brain responses to stress. We sought to characterize the impact of childhood abuse and neglect on the neural correlates of stress- and drug cue-induced drug craving associated with cocaine addiction. Cocaine-dependent men with (n=20) and without (n=18) moderate to severe childhood maltreatment histories underwent fMRI during script-guided mental imagery of personalized stress, drug use, and neutral experiences. Compared to the neutral script, the stress and drug use scripts activated striatal, prefrontal, posterior cingulate, temporal and cerebellar regions consistent with prior studies of induced states of stress and drug craving. For the stress script, maltreated men exhibited reduced activation of the anterior precuneus and supplementary motor area (SMA); the interaction of maltreatment severity and stress-induced craving responses predicted lesser rostral anterior cingulate cortex activation. For the drug use script, maltreated men exhibited greater left dorsolateral prefrontal cortex activation. The interaction of maltreatment severity and craving responses was associated with greater activation of the visual cortex and SMA, whereas a maltreatment-by-anxiety interaction effect included lesser ventromedial prefrontal cortex activation. The outcomes indicate an association of childhood maltreatment with a heightened appetitive anticipatory response to drug cues and a diminished engagement of regulatory and controlled action selection processes in response to stress- or drug cue-induced drug craving and anxiety responses for cocaine-dependent men. These findings provide novel insights into possible brain mechanisms by which childhood maltreatment heightens risk for relapse in drug-dependent individuals
