Cannabis Use Amplified a Brain Marker of Psychosis Risk in Early-Stage Patients | Research

The takeaway

A PET imaging study found that cannabis use was associated with significantly lower MAO-B levels, a marker of astrocyte function, in the brains of people with early psychosis and high-risk states, with the strongest effects in the striatum.

Psychosis researchers, psychiatrists treating early-onset psychosis, neuroscientists studying the cannabis-psychosis mechanism.

Cannabis use amplified astrocyte dysfunction in early psychosis brains, especially in the striatum

What the researchers found

Cannabis use had a significant effect on MAO-B availability (F=12.57, p=0.001, Cohen's f=0.57), with a significant group-by-cannabis interaction (p=0.03) showing lower MAO-B in cannabis-using clinical groups. Lower MAO-B was more pronounced in striatal than cortical regions. The clinical high-risk group showed significantly lower MAO-B than healthy volunteers (Cohen's d=0.99).

Why it matters

This is one of the first studies to show that cannabis use may specifically worsen astrocyte dysfunction in people at risk for or experiencing early psychosis. The finding connects cannabis use to a concrete brain-level change (lower MAO-B in astrocytes) that is linked to dopamine elevation in psychosis.

The numbers in context

n=38 total (14 FEP, 7 CHR, 17 HV); cannabis effect F=12.57, p=0.001, Cohen's f=0.57; group-by-cannabis interaction F=3.82, p=0.03; CHR vs HV Cohen's d=0.99; striatal effects stronger than cortical.

How the study worked

PET brain imaging study using [11C]SL25.1188 radiotracer to measure MAO-B (an astrocyte marker) in 14 antipsychotic-free first-episode psychosis patients, 7 clinical high-risk individuals, and 17 healthy volunteers, controlling for tobacco and cannabis use.

What this study cannot tell us

Small sample sizes, especially the CHR group (n=7). Cross-sectional design cannot determine temporal direction. Cannabis use was not the primary exposure of interest. Cannot determine whether cannabis directly causes lower MAO-B or whether individuals with lower MAO-B are more likely to use cannabis.

How to read the evidence

Moderate: PET imaging provides direct brain-level evidence with strong effect sizes, though small sample sizes (especially CHR n=7) limit generalizability.

When this study was published

Published in 2025.

The bigger picture

Astrocyte dysfunction is an emerging focus in schizophrenia research, supported by post-mortem, genetic, and preclinical evidence. This study adds cannabis as a factor that may exacerbate astrocyte problems in vulnerable individuals, offering a potential biological mechanism for the cannabis-psychosis link.

Questions still open

Does cannabis directly reduce MAO-B in astrocytes, or is this an indirect effect? Would cannabis cessation normalize MAO-B levels? Could MAO-B imaging identify individuals at highest risk for cannabis-related psychosis?

Common questions

What is MAO-B and why does it matter for psychosis?

MAO-B (monoamine oxidase B) is an enzyme found primarily in astrocytes, a type of brain cell. It helps break down dopamine. Lower MAO-B means less dopamine breakdown, which is consistent with the dopamine excess found in psychosis. Astrocyte dysfunction is increasingly recognized as part of schizophrenia biology.

Does this prove cannabis causes psychosis?

No, but it provides a biological mechanism by which cannabis could worsen psychosis risk. The study found that cannabis use was associated with lower MAO-B specifically in clinical groups (not healthy volunteers), suggesting cannabis may interact with pre-existing vulnerability rather than affecting all brains equally.

Read the original research

Evidence of altered monoamine oxidase B, an astroglia marker, in early psychosis and high-risk state.

Molecular psychiatry, 30(5), 2049-2058

View on PubMed ↗Publisher’s paper ↗

Citation

Nisha Aji, Kankana; Lalang, Nittha; Ramos-Jiménez, Christian; Rahimian, Reza; Mechawar, Naguib; Turecki, Gustavo; Chartrand, Daniel; Boileau, Isabelle; Meyer, Jeffrey H; Rusjan, Pablo M; Mizrahi, Romina. (2025). Evidence of altered monoamine oxidase B, an astroglia marker, in early psychosis and high-risk state.. Molecular psychiatry, 30(5), 2049-2058. https://doi.org/10.1038/s41380-024-02816-x