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In recent years, an abundant scientific literature has highlighted the psychotic effects of tetrahydrocannabinol (THC), the main active substance in cannabis. However, the precise mechanisms by which this molecule alters brain function remain partially elucidated. While factors like genetics or frequency of consumption play an obvious role, a recent study led by researchers at McGill University reveals another key dimension: the impact of cannabis on brain connectivity. Their work shows that this substance disrupts neuronal processes in young adults predisposed to psychosis, contributing to worsening certain brain deficits.
The human brain, particularly during critical phases of its development, engages in an important process known as synaptic pruning. This mechanism consists of optimizing neural networks by strengthening the most used synapses while eliminating those that are less used. This fine regulation is essential for learning, mastering language and even motor coordination. However, this process is not fixed: it can be influenced by environmental or social factors, and when these influences become deleterious, brain functioning can be compromised.
In a study aimed at observing structural changes in the brain in young adults at risk of psychosis, researchers at McGill University found that cannabis use directly interferes with this process of synaptic pruning. The team highlighted a significant reduction in neuronal connections, what we call synaptic density. “ Cannabis appears to disrupt the natural process of refining brain synapses, which is essential for healthy development“, said Romina Mizrahi, professor in the department of psychiatry at McGill University, in a press release.
The team's work, carried out between 2021 and 2023, was based on the in-depth analysis of 49 participants recruited in a tertiary care psychiatric hospital. Aged 16 to 30, they were divided into three groups: patients who had experienced a first psychotic episode, individuals identified as at high clinical risk (CHR) and a control group. All were subjected to medical, psychiatric and MRI examinations aimed at assessing their brain activity and neuronal connectivity.
« We targeted patients at the very beginning of their psychotic episode, often characterized by marked clinical severity, due to recruitment mainly carried out via emergency departments. », specify the researchers in their study document, published in the journalJAMA Psychiatry.
Towards new therapeutic perspectives
To precisely measure synaptic density, scientists focused on the SV2A protein, present in synaptic vesicles that store neurotransmitters. Their observations indicate a notable reduction in SV2A levels in patients who have experienced a first psychotic episode or identified as at high clinical risk. This reduction is also correlated with symptoms that are particularly resistant to traditional treatments, such as social withdrawal.
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These results, which support previous studies linking cannabis to reduced SV2A levels, could contribute to the development of new therapeutic approaches. “Current treatments mainly aim to reduce hallucinations, but they remain less effective on certain symptoms affecting daily life, such as managing social relationships or professional integration.,” explains Belen Blasco, a PhD student in neuroscience at McGill University. “By specifically targeting synaptic density, we could consider therapies capable of improving not only social functions, but also the overall quality of life of those affected.».
