Young adults at risk of psychosis show reduced brain connectivity, a deficit that cannabis use appears to worsen, a new study has found. The breakthrough paves the way for psychosis treatments targeting symptoms that current medications miss. In the first-of-its-kind study, McGill University researchers detected a marked decrease in synaptic density—the connections between neurons that enable brain communication—in individuals at risk of psychosis, compared to a healthy control group. “Not every cannabis user will develop psychosis, but for some, the risks are high. Our research helps clarify why,” said Dr. Romina Mizrahi, senior author of the study and professor in McGill’s Department of Psychiatry. “Cannabis appears to disrupt the brain’s natural process of refining and pruning synapses, which is essential for healthy brain development.” Hope for new treatments Using advanced brain scanning technology, the team studied 49 participants aged 16 to 30, including individuals with recent psychotic symptoms and those considered at high risk. The results, published in JAMA Psychiatry, indicate that lower synaptic density is linked to social withdrawal and lack of motivation, symptoms the researchers say are difficult to treat. “Current medications largely target hallucinations, but they don’t address symptoms that make it difficult to manage social relationships, work, or school,” said first author Belen Blasco, a PhD student at McGill’s Integrated Program in Neuroscience. “By focusing on synaptic density, we may eventually develop therapies that enhance social function and quality of life for those affected.” While cannabis is a known risk factor for developing psychosis, which can progress to schizophrenia, this is the first time researchers have measured structural changes in the brains of a high-risk population in real time. The team’s next research phase will explore whether these observed brain changes could predict psychosis development, potentially enabling earlier intervention. The study was conducted at the Douglas Mental Health University Institute and McGill University’s Montreal Neurological Institute-Hospital. It was supported by the Canadian Institute of Health Research. About the study "Synaptic Density in Early Stages of Psychosis and Clinical High Risk" by Belen Blasco, Kankana Nisha Aji, and Romina Mizrahi et al. was published in Jama Psychiatry.