Summary: New research provides a breakthrough in understanding the biological mechanisms linking Cannabis Use Disorder (CUD) and psychosis. By conducting a large-scale genetic meta-analysis, researchers identified over 500 genetic loci associated with psychosis, including 122 new associations.
The study reveals that the causal link from cannabis use to psychosis is driven by distinct biological pathways, including neurodevelopment and neuronal signaling, offering a new foundation for identifying high-risk individuals and developing targeted treatments.
Key Research Findings
- The Bidirectional Link: The study confirms a bidirectional causal association between psychosis and cannabis use. However, the magnitude of the causal association is significantly larger from CUD to psychosis than the reverse.
- Three Distinct Mechanisms: For the first time, researchers identified three distinct groups of genetic variants involved in the path from CUD to psychosis. These genes are critical in:
- Neurodevelopment
- Neuronal Signaling
- Other biological processes
- The Glutamate System: Analysis of genetic scores suggests that genes involved in the glutamate system may be key in identifying who is at the greatest risk of developing psychosis when using cannabis. The glutamate system is known to be directly affected by THC.
- A Broader Perspective: Unlike previous studies focused solely on schizophrenia, this team analyzed genome-wide association studies for both schizophrenia and bipolar 1 disorder to create a more comprehensive “psychosis clinical group”.
- Clinical Reflection: Only one group of causal genetic variants was identified from psychosis to CUD, mirroring clinical observations of less variation in how pre-existing psychosis leads to heavy cannabis use.
Source: King’s College London
New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London has highlighted the distinct and shared molecular pathways linking cannabis use disorder (CUD) and psychosis, offering the potential for identifying those at risk, as well as targeted interventions for cannabis related psychosis.
The research, published in Biological Psychiatry Global Open Science, provides new evidence for the biological mechanisms underlying the causal association between cannabis use and psychosis, and points to distinct biological pathways that may explain how cannabis use leads to psychosis
While previous research has suggested that cannabis use is associated with an increased risk of psychotic disorders, the underlying biological mechanisms remain unclear. Researchers in this study set out to use updated genetic data to investigate the molecular pathways contributing to CUD and psychosis.
The research team conducted a meta-analysis of genome-wide association studies of people with schizophrenia and bipolar 1 disorder. This created a broader psychosis clinical group, beyond schizophrenia alone, which more closely reflects epidemiological reports of cannabis use and psychosis.
Their analysis of the data identified over 500 genetic loci associated with psychosis, which includes 122 novel associations. Genetic pathway analysis using this data showed that more biological pathways were nominally associated with psychosis and CUD than expected by chance, suggesting the close link between the two.
Professor Marta Di Forti, Professor of Drug use, Genetics and Psychosis at King’s IoPPN and the study’s senior author said, “As conversations around cannabis use increasingly turn to whether it should be legalised, there is an ever increasing need to improve how we identify those at greatest risk from heavy use, as well as to develop tailored interventions for those who have experience psychosis in the context of cannabis use.
“Our study supports previous evidence of a bidirectional causal association between psychosis to cannabis use, but importantly with a larger magnitude of causal association from CUD to Psychosis.
“Moreover, for the first time the study shows three distinct groups of genetic variants likely to be involved in causal association from CUD to psychosis, including genes important in neurodevelopment, neuronal signaling and other processes.
“This can potentially explain how cannabis use leads to psychosis. Only one group of causal genetic variants was identified from psychosis to CUD, suggesting less variation in how psychosis can lead to heavy cannabis use; reflecting what we see in clinic.
“Lastly, our novel analyses of genetic scores for specific neurotransmitters, suggested that genes involved in the glutamate system might help in the future to identify those at greater risk to develop psychosis when using cannabis. The glutamate system is known to be affected by THC.
“In time, this could provide the groundwork for prediction models that identify those most at risk, as well as informing the development of new targeted treatments.”
Dr Isabelle Austin-Zimmerman, a research associate at King’s IoPPN and the study’s first author said, “What these findings reveal is that the biology linking cannabis use and psychosis is complex and might work through multiple mechanisms. This is a step towards understanding the potentially different etiology in psychosis with and without cannabis use.”
Key Questions Answered:
A: The research shows it is both, but the effect of cannabis use leading to psychosis is much stronger. It effectively identifies three specific “routes” in the DNA that explain how heavy cannabis use can trigger a psychotic break.
A: THC, the main psychoactive part of cannabis, directly impacts glutamate. Since researchers found that genes regulating glutamate help determine psychosis risk, this could lead to future tests that tell a person if their specific brain chemistry makes cannabis use “high risk” for them.
A: Yes. By understanding that psychosis with cannabis use has a different biological “fingerprint” than psychosis without it, doctors can develop more tailored, targeted interventions rather than using a one-size-fits-all approach.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this genetics and CUD research news
Author: Patrick O’Brien
Source: King’s College London
Contact: Patrick O’Brien – King’s College London
Image: The image is credited to Neuroscience News
Original Research: The findings will appear in Biological Psychiatry Global Open Science
