Psychosis may arise from the brain incorrectly assigning novelty and importance to ordinary objects and associations, a process linked to dopamine's role in reward prediction and motivational salience. Antipsychotics block dopamine receptors, reducing this aberrant salience and creating a state of detachment from symptoms rather than eradicating them. Contrary to the idea of a delayed onset, improvement is evident within the first few days. The framework accounts for existing data and questions assumptions about antipsychotic action, including their effects in animal models, where they dampen both aberrant and normal motivational salience.
Long-term cannabis users (26 participants) and non-using controls (47 participants) underwent brain scans measuring chemicals in the anterior cingulate cortex. Markers of glial function and glutamate metabolism did not differ between groups overall. However, lower myo-inositol, a glial marker, was linked to more problematic drug use and greater cannabis dependence severity. Past-year cannabis exposure affected glutamate metabolites differently by sex: greater exposure was associated with higher glutamate levels in male users but not in female users. These findings suggest that cannabis use may alter brain chemistry in ways related to problematic use and that sex differences exist in these effects.