We know there’s a link between cannabis use and psychosis, though the odds vary widely from study to study. But it’s still unclear exactly how the drug triggers psychosis, which can progress to schizophrenia.
Genes, drug potency, and age of use all appear to play a role, and scientists in Canada have just uncovered another important factor: brain connectivity.
The study found that young people in the early stages of psychosis, or showing signs of being at-risk, had noticeably lower density in their brain synapses.
“Not every cannabis user will develop psychosis, but for some, the risks are high. Our research helps clarify why,” says neuropharmacologist Romina Mizrahi, from McGill University.
The researchers analyzed data from 49 participants, ages 16 to 30, from a tertiary care psychiatric hospital between July 2021 and October 2023.
Among the group were people who had experienced their first episode of psychosis or were considered ‘clinical high risk’ (CHR), and healthy controls. All were either not taking antipsychotics or only taking minimal doses, and tested negative in drug screening for anything besides cannabis.
Participants also underwent medical and psychiatric screening, and PET and MRI scans, to measure their symptoms, brain structure and composition, and identify any potential confounding factors.
“We included patients with very recent psychotic onset and higher clinical severity as we primarily recruited from the emergency department,” the authors note.
They assessed synaptic density by looking for levels of a protein called SV2A. Scientists use this protein as an indicator because it hangs out on the synaptic vesicles that store your neurotransmitters; generally, the more SV2A in your brain, the more synapses they can assume you’ve got packed into there.
The study also showed that lower synaptic density was associated with higher scores of negative psychiatric symptoms among participants with first-episode psychosis or CHR. The authors say it’s the first study to provide direct evidence of changes in the synapses of patients during CHR states.
Knowing that there’s less of this protein kicking around in the brains of people who have experienced their first episode of psychosis, or who are at high clinical risk for it, also helps us understand how cannabis might be sparking the match.
That’s because, in tandem, the researchers found that using cannabis actually lowers SV2A levels, and therefore synaptic density, which lines up with the findings of a previous study that found SV2A levels were reduced in people with cannabis use disorder.
“Cannabis appears to disrupt the brain’s natural process of refining and pruning synapses, which is essential for healthy brain development,” Mizrahi explains.
Notably, they found cannabis use was impacting the striatal regions of the brain, which are known to be involved in psychosis.
It’s important to bear in mind that the study doesn’t show that cannabis use necessarily caused the reduced synaptic density in psychosis patients, or vice versa.
The study has a pretty small sample size, with participants in only the early stages of experiencing psychosis, for which long-term outcomes can vary widely. The team also notes that while SV2A can indicate synaptic density, it’s not a direct measure.
But the fact that a change in SV2A levels is present in both the early stages of psychosis and in cannabis use is certainly interesting. The team thinks its worth investigating the impact cannabis use has on synaptic density as a potential mechanism for psychosis conversion, among those at high risk.
“Current medications largely target hallucinations, but they don’t address symptoms that make it difficult to manage social relationships, work, or school,” says neuroscience PhD student Belen Blasco, from McGill.
“By focusing on synaptic density, we may eventually develop therapies that enhance social function and quality of life for those affected.”
This research is published in JAMA Psychiatry.
