Scientists Identify a Brain ‘Weak Spot’ That May Explain How Cannabis Triggers Psychosis

Researchers from the Perelman School of Medicine at the University of Pennsylvania have identified a possible biological mechanism that may explain the link between cannabis use and the development of psychotic symptoms. The findings were published in the journal Molecular Psychiatry.

Psychosis is a severe mental disorder in which a person loses touch with reality. It can involve hallucinations, delusions, and disorganized thinking. Although previous studies have consistently linked frequent cannabis use to an increased risk of psychosis, the biological basis for this association has remained unclear.

In the new study, researchers suggest that glutamate—one of the brain’s primary neurotransmitters responsible for communication between nerve cells—may play a key role.

The study included 79 participants: healthy volunteers, individuals at high risk of developing psychosis, and patients with an established psychotic disorder. Participants underwent psychiatric evaluations, reported their cannabis use, and provided biological samples to confirm recent exposure to the drug.

The researchers also used ultra-high-field 7-tesla magnetic resonance spectroscopy to measure glutamate levels in the anterior cingulate cortex, a brain region involved in emotion regulation, decision-making, and information processing.

The analysis showed that both cannabis use and lower glutamate levels were independently associated with more severe psychotic symptoms. The strongest association was observed among cannabis users: the lower the glutamate concentration, the more pronounced the hallucinations and delusions.

Patients with psychosis—particularly those who used cannabis—had lower glutamate levels than the other participants. According to the researchers, this suggests that dysfunction of the glutamate system may amplify the harmful effects of cannabis on the brain.

The authors believe that further research into the glutamate system could lead to new strategies for preventing and treating mental disorders associated with cannabis use.

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