Cannabis Users Had Lower Brain Synaptic Density in Early Psychosis PET Scans | Research

The takeaway

PET brain imaging found reduced synaptic density in people with early psychosis and those at clinical high risk, with cannabis users showing even lower levels across all groups.

Psychiatrists, neuroscience researchers, anyone interested in the biological link between cannabis and psychosis

Cannabis users had significantly lower brain synaptic density across all diagnostic groups

What the researchers found

Synaptic density (measured by SV2A binding) was significantly lower in first-episode psychosis and clinical high-risk participants compared to healthy controls. Cannabis users had additionally lower synaptic density regardless of diagnostic group. Lower synaptic density was associated with more severe negative symptoms.

Why it matters

This is one of the first studies to measure synaptic density in vivo during the earliest stages of psychosis. The finding that cannabis use is associated with even lower synaptic density suggests cannabis may compound the synaptic loss already occurring in psychosis development.

The numbers in context

49 participants total; synaptic density significantly different between groups (F2,273 = 4.02, P = .02); cannabis users had lower density (F1,272 = 5.31, P = .02); lower density associated with negative symptoms on both PANSS (P = .04) and SOPS (P = .04); SV2A binding correlated with neurite density (P = .01)

How the study worked

Cross-sectional study using [18F]SynVesT-1 PET scans and diffusion-weighted MRI in 49 participants: 16 with first-episode psychosis, 17 at clinical high risk, and 16 healthy controls. Cannabis use was confirmed by urine drug screens. Participants were antipsychotic-free or minimally exposed.

What this study cannot tell us

Small sample (49 participants), cross-sectional design cannot determine whether cannabis caused lower synaptic density, cannot rule out confounding factors, limited to specific brain regions of interest

How to read the evidence

Small but methodologically rigorous PET imaging study with antipsychotic-free participants; novel in vivo synaptic density measurement

When this study was published

Published 2025

The bigger picture

Schizophrenia research increasingly points to synaptic dysfunction as a core feature. This study suggests the synaptic damage may begin before full psychosis develops and that cannabis use could accelerate this process, adding biological specificity to the well-documented cannabis-psychosis association.

Questions still open

Does cannabis use directly cause synaptic loss, or do people with lower synaptic density gravitate toward cannabis use? Would synaptic density recover with cannabis cessation? Could SV2A PET scans help identify who is most vulnerable to cannabis-related psychosis risk?

Common questions

What is synaptic density and why does it matter for psychosis?

Synaptic density reflects the number of connections between brain cells. This study found it was reduced in early psychosis and even lower in cannabis users, suggesting cannabis may compound the connection loss that occurs as psychosis develops.

Does this prove cannabis damages brain synapses?

No. The cross-sectional design cannot determine cause and effect. It is possible that people with naturally lower synaptic density are more likely to use cannabis, rather than cannabis causing the reduction.

Read the original research

Synaptic Density in Early Stages of Psychosis and Clinical High Risk.

JAMA psychiatry, 82(2), 171-180

View on PubMed ↗Publisher’s paper ↗

Citation

Blasco, M Belen; Nisha Aji, Kankana; Ramos-Jiménez, Christian; Leppert, Ilana Ruth; Tardif, Christine Lucas; Cohen, Johan; Rusjan, Pablo M; Mizrahi, Romina. (2025). Synaptic Density in Early Stages of Psychosis and Clinical High Risk.. JAMA psychiatry, 82(2), 171-180. https://doi.org/10.1001/jamapsychiatry.2024.3608