New research from King’s College London asks one of the most pressing questions in mental health science: why does cannabis use raise the risk of psychosis in some people but not others? Scientists published the findings in Biological Psychiatry: Global Open Science in 2026. They point to a complex web of shared genes and biological pathways that may one day help identify the most vulnerable individuals early.
For anyone who has seen a young person’s mental health deteriorate alongside heavy cannabis use, this research feels significant. It moves the conversation beyond statistics and into biology, offering a clearer picture of what actually happens at the molecular level.
What the Genetics Reveal About Cannabis Use and Psychosis Risk
The team at the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) conducted a large scale genetic analysis drawing on data from over 547,000 participants. Rather than study schizophrenia alone, they built a broader “combined psychosis” group that also included bipolar I disorder. This better reflects how cannabis related psychosis presents in real life.
Their analysis uncovered more than 550 genetic locations linked to psychosis, including 122 entirely new associations. They also found that far more biological pathways overlap between cannabis use disorder and psychosis than chance alone would predict. This strongly suggests the two conditions share genuine biological roots, not simply co-occurring for social or lifestyle reasons.
Using a method called Mendelian randomisation, researchers confirmed that cannabis use disorder causally raises the risk of psychosis. That causal effect ran stronger from cannabis use to psychosis than in the reverse direction.
Three Distinct Routes from Cannabis Use Disorder to Psychosis
At least three separate genetic clusters drive the link from cannabis use disorder to psychosis. Each cluster points to a different biological mechanism, which helps explain why the relationship looks so varied in clinical settings.
The first and third clusters involve genes tied to synaptic signalling and neuronal development. Cannabis may disrupt how nerve cells connect and communicate, especially during critical windows of brain development in adolescence and early adulthood.
The second cluster carries the strongest genetic signals. It connects to intracellular signalling, epigenetic regulation, and gene expression. In plain terms, heavy cannabis use may alter how genes switch on or off. Those changes could contribute to the onset of psychotic illness.
Only one causal cluster ran in the opposite direction, from psychosis to cannabis use. This suggests less biological variation in why people with psychosis might turn to cannabis, which mirrors what clinicians tend to observe.
The Glutamate Connection and Cannabis Use and Psychosis Risk
One system appeared consistently across every analysis: the glutamate pathway. Glutamate is the brain’s primary excitatory neurotransmitter, and scientists have long linked disruption in this system to psychosis.
Genetic scores built around glutamate related genes were the strongest predictors of psychosis across the entire sample. Those scores remained predictive both in cannabis users and in people who had never used the drug, though the effect was particularly strong among users.
THC, the psychoactive compound in cannabis, acts on CB1 receptors that sit on glutamatergic neurons. The research team suggests cannabis may amplify an existing underlying vulnerability in this system, potentially tipping susceptible individuals towards psychosis.
Professor Marta Di Forti, the study’s senior author, put it plainly: genes involved in the glutamate system might one day help identify those at greater risk of developing psychosis when using cannabis.
Why Cannabis Use and Psychosis Risk Research Matters Now
Cannabis sits among the most widely used substances in the world. Debates about legalisation continue across many countries, and that makes understanding who carries the greatest risk far more than an academic exercise.
Among cannabis users, genetic vulnerabilities in neuronal pathways, covering axon development, dendritic structure, and synaptic function, all associated with higher psychosis risk. This raises a real prospect: developing tools that flag high risk individuals before psychosis takes hold.
Biological pathways tied to GABAergic signalling and calcium channel activity lost significance once researchers statistically removed cannabis use from the equation. Those pathways may therefore be specific to cannabis related psychosis rather than psychosis in general. That distinction could eventually point towards more targeted clinical approaches.
What This Research Means Going Forward
This study adds weight to a growing body of evidence. The link between cannabis use and psychosis risk is not simply a lifestyle or environmental story. Genetics play a real part, and the biological picture is becoming clearer.
The study carries important caveats. Researchers drew data almost entirely from people of European ancestry, which limits how widely the findings apply globally. The pathway based genetic scores are exploratory and need replication in larger samples before anyone could use them in practice.
Still, the direction is clear. Science around cannabis use disorder and psychosis is becoming more precise. The hope is that greater precision will eventually translate into better identification of those most at risk and more targeted support for those already affected. (Source: WRD News)
Also See:
- All Young Cannabis Users Face Psychosis Risk
- Cannabis & Psychosis – Irrefutable
- C.I.P – Cannabis Induced Psychosis