AIMS:To understand processes placing individuals at risk for stimulant (amphetamine and cocaine) use disorder. DESIGN:Longitudinal study. SETTING:University of California, San Diego Department of Psychiatry, CA, USA. PARTICIPANTS:Occasional stimulant users (OSU; n = 184) underwent a baseline clinical interview and a functional magnetic resonance imaging (fMRI) session. On the basis of a follow-up clinical interview completed 3 years later, OSU (n = 147) were then categorized as problem stimulant users (PSU: n = 36; those who developed stimulant use disorders in the interim) or desisted stimulant users (DSU: n = 74; those who stopped using). OSU who did not meet criteria for PSU or DSU (n = 37) were included in dimensional analyses. MEASUREMENTS:fMRI blood oxygen level-dependent (BOLD) contrast percentage signal change from baseline collected during a Paper-Scissors-Rock task was examined during three decision-making conditions, those resulting in: (1) wins, (2) ties and (3) losses. These data were used as dependent variables in categorical analyses comparing PSU and DSU, as well as dimensional analyses including interim drug use as predictors, controlling for baseline drug use. FINDINGS:PSU exhibited lower anterior cingulate, middle insula, superior temporal, inferior parietal, precuneus and cerebellum activation than DSU across all three conditions (significant brain clusters required > 19 neighboring voxels to exceed F(1,108) = 5.58, P < 0.01 two-tailed; all Cohen's d > 0.83). Higher interim marijuana use was linked to lower pre-central and superior temporal activation during choices resulting in wins (> 19 neighboring voxels to exceed t = 2.61, P < 0.01 two-tailed; R2 change > 0.11). CONCLUSIONS:Individuals who transition from stimulant use to stimulant use disorder appear to show alterations in neural processing of stimulus valuation and outcome monitoring, patterns also evident in chronic stimulant use disorder. Attenuated anterior cingulate and insular processing may constitute a high-risk neural processing profile, which could be used to calculate risk scores for individuals experimenting with stimulants.