Abstract
Substance use and substance use disorders represent ongoing major public health crises. Specifically, the use of substances such as cocaine and heroin are responsible for over 50,000 drug-related deaths combined annually. We used a comparative meta-analysis procedure to contrast activation patterns associated with cocaine and heroin cue reactivity, which may reflect substance use risk for these substances. PubMed and Google Scholar were searched for studies with within-subject whole brain analyses comparing drug to neutral cues for users of cocaine and heroin published between 1995 and 2022. A total of 18 studies were included, 9 in each subgroup. Voxel-based meta-analyses were performed using seed-based d mapping with permuted subject images (SDM-PSI) for subgroup mean analyses and a contrast meta-regression comparing the two substances. Results from our mean analysis indicated that users of heroin showed more widespread activation in the nucleus accumbens, right inferior and left middle temporal gyrus, right thalamus, and right cerebellum. Cocaine use was associated with recruitment of dorsolateral prefrontal cortex during cue reactivity. Direct comparison of cue reactivity studies in heroin relative to cocaine users revealed greater activation in dopaminergic targets for users of heroin compared to users of cocaine. Differential activation patterns between substances may underlie differences in the clinical characteristics observed in users of cocaine and heroin, including seeking emotional blunting in users of heroin. More consistent research methodology is needed to provide adequate studies for stringent meta-analyses examining common and distinct neural activation patterns across substances and moderation by clinically relevant factors.