Study links lower brain glutamate and cannabis use with psychosis symptoms

Cannabis use has been associated with a higher risk of psychosis in earlier research, but scientists do not yet know exactly why. Psychosis describes a disrupted sense of reality that can include hallucinations, delusions, or disorganized thinking.

In this study, researchers examined whether glutamate might be part of the picture. Glutamate is a chemical messenger that helps brain cells communicate. The team focused on the anterior cingulate cortex, a region near the front of the brain.

The study included 79 participants across what the researchers called the psychosis spectrum. This included typically developing controls, people considered at clinical high risk of psychosis, and patients with psychosis. Participants completed assessments of symptoms, detailed surveys about cannabis use, and urine testing. They also had a specialized 7 Tesla magnetic resonance spectroscopy scan, which can measure certain brain chemicals without surgery.

The researchers found that lower glutamate levels in the anterior cingulate cortex and higher cannabis use were each independently associated with more positive and negative psychosis symptoms. Positive symptoms include experiences added to a person’s usual experience, such as hallucinations or delusions. Negative symptoms include reduced motivation, less ability to feel pleasure, social withdrawal, or limited emotional expression.

The study’s central finding was an interaction between cannabis use and glutamate. Among people who used cannabis, lower glutamate was associated with more positive psychosis symptoms. This pattern was not seen in people who did not use cannabis.

The researchers also reported exploratory findings involving depressive and manic symptoms. These analyses suggested that glutamate differences could be linked with greater overall symptom severity related to cannabis use. In additional analyses, people with psychosis had lower glutamate levels, especially those who used cannabis.

Importantly, these results show associations, not cause and effect. The study did not establish whether cannabis use lowers glutamate, whether lower glutamate makes someone more vulnerable to symptoms, or whether symptoms and other factors affect cannabis use. It also cannot tell whether the same patterns would appear in larger or different groups of people.

The research was completed at one point in time rather than following participants over time. That makes it useful for identifying patterns, but not for showing which change came first. The abstract also does not provide effect sizes, participant demographics, or the number of people in each study group.

The authors say future longitudinal studies, which follow people over time, will be needed to test possible causal pathways. They also note that research into treatments that target glutamate would be needed before any conclusions could be drawn about whether changing this brain chemical could affect cannabis-related psychosis symptoms.

For now, the findings offer a possible clue about brain biology rather than a proven explanation. They reinforce that the relationship between cannabis, brain chemistry, and psychosis symptoms is complex and remains under study.