A study published in JAMA Psychiatry, sheds new light on the long-debated connection between cannabis use and psychosis. Led by researchers from McGill University and Western University, the study employs a cutting-edge imaging technique to trace how cannabis use disorder (CUD) interacts with dopamine pathways in the brain—providing a possible biological explanation for the increased risk of psychotic disorders among cannabis users.
The study focused on the midbrain’s substantia nigra and ventral tegmental area (SN/VTA), regions crucial to dopamine production and long implicated in schizophrenia. Using neuromelanin-sensitive magnetic resonance imaging (neuromelanin-MRI), a noninvasive marker for long-term dopamine activity, researchers observed elevated dopamine-related signals in individuals with CUD—even in those without schizophrenia.
The study included 61 participants, both with and without CUD, some of whom also had first-episode schizophrenia (FES). Strikingly, individuals with CUD showed significantly increased neuromelanin-MRI signals in specific SN/VTA regions previously linked to untreated psychosis. This pattern was particularly evident in a cluster of 387 brain voxels associated with dopamine turnover. Even more revealing was the dose-dependent effect: the more severe the cannabis use, the stronger the signal—a clear indication that continued cannabis exposure may amplify dopaminergic activity in psychosis-sensitive areas.
Interestingly, participants diagnosed with schizophrenia alone did not show such elevated signals, which the authors suggest may be due to early antipsychotic treatment normalizing dopamine function. However, among those with both CUD and FES, the dopamine signal was nearly twice as strong as in those with CUD alone, hinting at an additive effect that could further intensify psychosis risk.
One of the study's most compelling findings is that elevated dopamine-related signals persisted over a year in participants with ongoing cannabis use. This challenges earlier studies using PET scans that found blunted dopamine release in chronic cannabis users. According to the researchers, this discrepancy may reflect differences in participant age, cannabis dependence severity, or imaging modality.
But what does an elevated neuromelanin-MRI signal really mean? Neuromelanin, a byproduct of dopamine metabolism, builds up in brain cells over time and is thought to be a marker of cumulative dopamine activity. While it may have protective antioxidant properties, chronic elevation can indicate prolonged dopaminergic stress—an underlying factor in the development of psychotic symptoms.
While the authors caution that causality can’t yet be definitively established, their findings provide a strong case for cannabis use impacting the same “final common pathway” in the brain that drives psychosis. They also emphasize the need for larger, long-term studies to explore whether heightened neuromelanin levels precede CUD—or result from it.
The full article, “Convergence of Cannabis and Psychosis on the Dopamine System,” is available open-access at JAMA Psychiatry: https://doi.org/10.1001/jamapsychiatry.2025.0432
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