Abstract
Addiction theories posit that addiction is the result of a progressive transition from voluntary to habitual, compulsive drug use—changes that have been linked, in animals, to a shift from ventral to dorsal striatal control over drug-seeking behavior. Thus, we hypothesized that early-onset (EOs) cannabis users versus late-onset (LOs) cannabis users might exhibit, respectively, greater dorsal versus ventral striatal response to drug cues. We used functional magnetic resonance imaging and an event-related blood oxygen level-dependent backward-masking task to evaluate striatal responses to backward-masked cannabis cues (vs. neutral cues) in EOs (<16 years old, n=15) and LOs (≥16 years old, n=26) with similar recent cannabis use patterns. Direct comparisons revealed that EOs showed greater response to cannabis cues in the dorsal striatum than LOs (p<0.01, k>50 voxels). Within-group analyses revealed that EOs showed greater neural response to cannabis cues in the dorsal striatum, whereas LOs exhibited greater neural response to cannabis cues in the ventral striatum. Although cross-sectional, these findings are consistent with recent addiction theories suggesting a progressive shift from ventral to dorsal striatal control over drug-seeking behavior and highlight the importance of age of onset of cannabis use on the brain and cognition.
Highlights
Cannabis is the most widely used psychoactive substance.[1]
Direct comparisons of neural responses to backwardmasked cannabis cues compared to neutral cues between EOs and LOs revealed that EOs showed significantly greater response in the dorsal striatum than LOs ( p < 0.01, k > 50 voxels)
As hypothesized, preliminary analyses revealed that EOs and LOs showed different patterns of neural response to backward-masked cannabis cues, with EOs showing greater response within the dorsal striatum compared to LOs
Summary
Cannabis is the most widely used psychoactive substance.[1]. In the United States, *22.2 million people aged 12 or older report using cannabis in the past month,[2] and numbers will likely increase as states continue to legalize cannabis for medicinal and recreational purposes.[3]. Addiction theories posit that substance use disorders are the result of ‘‘a series of transitions from initial voluntary drug use to habitual, and compulsive drug use’’9 (p.1946). These transitions include a shift from ventral to dorsal striatal control over behaviors (and impaired prefrontal inhibitory control) that contribute to habitual and progressively compulsive drug seeking.[10,11,12] The majority of the research supporting this theory has been conducted in animal models; recent human studies on age of onset of cannabis use may provide additional support for such brain changes and impairments in prefrontal inhibitory control. Early (before age 16) onset of cannabis use (EO) has been associated with structural connectivity differences of the orbitofrontal cortex (OFC),[13]
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