Study identifies genetic pathways linking cannabis use and psychosis

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.”