There exists a well-documented correlation between cannabis use and the onset of psychosis, albeit the likelihood varies significantly across disparate studies. However, the precise mechanisms through which cannabis induces psychosis, which may ultimately evolve into schizophrenia, remain enigmatic.

Factors such as genetic predispositions, the potency of the drug, and the age at which use begins evidently contribute to this phenomenon. Recent research conducted by scientists in Canada has illuminated an additional critical variable: the connectivity of the brain.

The investigation revealed that young individuals who are either in the nascent stages of psychosis or exhibiting indicators of being at elevated risk exhibit markedly diminished synaptic density within their cerebral structures.

“While not every individual who uses cannabis will develop psychosis, for some, the associated risks are pronounced. Our research elucidates the underlying reasons,” states neuropharmacologist Romina Mizrahi from McGill University.

Data was meticulously gathered from 49 participants aged 16 to 30, all recruited from a tertiary psychiatric care facility between July 2021 and October 2023. The cohort included individuals experiencing their inaugural episode of psychosis, those classified as clinically high risk, and a group of healthy controls. All subjects were either not medicated with antipsychotics or were prescribed minimal doses, with subsequent screenings confirming the absence of substances apart from cannabis.

Comprehensive medical and psychiatric assessments were conducted, alongside PET and MRI scans, to evaluate symptoms, brain structure, and composition while identifying any potential confounding factors.

The authors emphatically note that participants were predominantly recruited from emergency departments, specifically including those with very recent psychotic presentations and significant clinical severity. They evaluated synaptic density by examining levels of a protein known as SV2A, a reliable indicator of synaptic presence.

Moreover, the findings indicated a correlation between lower synaptic density and increased negative psychiatric symptomatology in patients experiencing their first psychotic episode or classified as clinically high risk. This study is pioneering in its provision of direct evidence regarding synaptic alterations in patients manifesting clinical high risk states.

The revelation that cannabis use is concomitant with reduced SV2A levels—hence diminished synaptic density—aligns with previous investigations outlining similar findings in individuals grappling with cannabis use disorder.

“Cannabis seems to disrupt the brain’s innate processes of synaptic refinement and pruning, crucial for optimal cognitive development,” elucidates Mizrahi.

Significantly, the research pinpointed the impact of cannabis usage on the striatal regions of the brain, regions intrinsically linked to psychotic phenomena. However, it is imperative to recognize that this study does not unequivocally establish causation between cannabis use and diminished synaptic density, as the relationship may be reciprocal.

Despite the relatively modest sample size and its focus on early-stage psychosis—an aspect notorious for its variable long-term prognosis—this investigation raises intriguing questions. The equipoise of SV2A alterations in both nascent psychosis and cannabis consumption merits further exploration of the drug’s potential mechanistic influences on synaptic density, particularly among individuals at high risk.

“Current pharmacological interventions predominantly target hallucinations, yet overlook the broader symptoms that hinder social integration and function,” remarks neuroscience PhD candidate Belen Blasco from McGill. “By concentrating on synaptic density, we might ultimately unveil therapeutic avenues that enhance social capabilities and overall quality of life for affected individuals.”

This research is published in JAMA Psychiatry.