Researchers reveal that daily use of high-potency cannabis significantly increases the risk of developing psychosis, regardless of genetic predisposition to schizophrenia.
This groundbreaking study, which used large datasets to explore the roles of cannabis use and genetic risk scores, found that the combination of genetic predisposition and frequent cannabis use elevates the likelihood of psychosis, highlighting the need for preventive measures among high-risk individuals.
Insights into Cannabis Use and Psychosis Risk
The results provide insight into possible future ways to identify those at higher risk of psychosis and help inform preventative strategies.
There is a well-established association between cannabis and psychosis but the underlying role of genetics in this relationship remains unclear. Polygenic risk scores (PRSs) summarise the estimated small effects of many common genetic variants on the risk of developing a disease or disorder. Recent advances in the collection and analysis of genetic data have enabled PRSs to be calculated for a range of disorders.
Genetic Mechanisms in Cannabis-Related Psychosis
Published in Psychological Medicine, the study aimed to explore the genetic mechanisms that underpin the relationship between heavy cannabis use and psychosis. Researchers worked with two large datasets to establish PRSs for schizophrenia and for cannabis use disorder to investigate their relationship to psychosis and patterns of cannabis use.
The research was supported by the Medical Research Council (MRC) and the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre (BRC). The data were from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) and the UK Biobank which are large cohorts that both contain data on genetics, self-reported cannabis use, and diagnoses of psychosis. There were 1592 participants from EU-GEI and 145,244 participants from UK Biobank.
Separate Pathways to Psychosis
In both samples, lifetime frequent cannabis use was associated with an increased likelihood of psychosis and this was highest among those who were daily users of high-potency cannabis. High potency cannabis was defined as having Delta-9 tetrahydrocannabinol (THC) content of 10 percent or more. This relationship remained the same when researchers accounted for the PRS for schizophrenia, suggesting that the environmental risk from cannabis use for psychosis is independent of the genetic risk.
“Our study is the first to estimate the risk of psychosis from both cannabis use and genetic predisposition to schizophrenia. Interestingly, we found no evidence of an interaction between the two, suggesting they influence the risk of psychosis through separate pathways and could potentially have an additive effect where those with increased genetic risk who use cannabis are highly likely to develop psychosis. Through further analysis of cannabis use of different frequencies and potencies, we have shown that highest risk for psychosis is in those with greater genetic predisposition to schizophrenia who use high potency cannabis daily.”
Dr. Edoardo Spinazzola, Research Assistant at King’s IoPPN, Consultant Adult Psychiatrist, South London and Maudsley NHS Foundation Trust and corresponding author on the paper
Polygenic Risk and Cannabis Use Patterns
In the EU-GEI cohort researchers found that schizophrenia PRS was not associated with an individual’s propensity to try cannabis or the frequency of use. In the UK Biobank there was also no association between schizophrenia PRS and cannabis use in those with a psychosis diagnosis. However, among those without psychosis in the UK Biobank, the PRS for schizophrenia was associated with lifetime and daily cannabis use, but the effect was substantially reduced when the PRS for cannabis use disorder was included in the model.
“These are important findings at a time of increasing use and potency of cannabis worldwide. Our study indicates that daily users of high potency cannabis are at increased risk of developing psychosis independently from their polygenic risk score for schizophrenia. Nevertheless, the polygenic risk score for schizophrenia might, in the near future, become useful to identify those at risk for psychosis among less frequent users to enable early preventative measures to be put in place.”
Professor Marta di Forti, Professor of Drug Use, Genetics and Psychosis at King’s IoPPN and lead author on the paper
Reference: “The impact of schizophrenia genetic load and heavy cannabis use on the risk of psychotic disorder in the EU-GEI case-control and UK Biobank studies” by Isabelle Austin-Zimmerman, Edoardo Spinazzola, Diego Quattrone, Beatrice Wu-Choi, Giulia Trotta, Zhikun Li, Emma Johnson, Alexander L. Richards, Tom P. Freeman, Giada Tripoli, Charlotte Gayer-Anderson, Victoria Rodriguez, Hannah E. Jongsma, Laura Ferraro, Caterina La Cascia, Sarah Tosato, Ilaria Tarricone, Domenico Berardi, Elena Bonora, Marco Seri, Giuseppe D’Andrea, Andrei Szöke, Celso Arango, Julio Bobes, Julio Sanjuán, Jose Luis Santos, Manuel Arrojo, Eva Velthorst, Miguel Bernardo, Cristina Marta Del-Ben, Paulo Rossi Menezes, Jean-Paul Selten, Peter B. Jones, James B. Kirkbride, Bart P. F. Rutten, Andrea Tortelli, Pierre-Michel Llorca, Lieuwe de Haan, Simona Stilo, Daniele La Barbera, Antonio Lasalvia, Franck Schurnhoff, Baptiste Pignon, Jim van Os, Michael Lynskey, Craig Morgan, EU-GEI WP2 Group, Michael O’ Donovan, Cathryn M. Lewis, Pak C. Sham, Robin M. Murray, Evangelos Vassos and Marta Di Forti, 6 December 2024, Psychological Medicine.
DOI: 10.1017/S0033291724002058
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5 Comments
I think studies such as these should be careful to know the strain of cannabis used. I find that indica is not as crazy-making as sativa.
Wow take a cold shower and eat some chips it’s just weed… If it makes you uncomfortable stop smoking it. Some people get violent when they drink, some don’t. We all react different to things don’t use blanket assumptions about everyone based on tests on select groups.
Wow About Time … I have Known plenty of people young and old all different backgrounds and I can tell you so many times when people smoke the high potency THC they don’t even realize they come across like they are addicted to Meth and not just to a little THC …..
Because yes this High THC has caused many people to freak out saying people are out to get them, people or something is trying to kill them , someone is always watching them so they are up all hours of the night , they become SO FORGETFUL even Years after Last time they smoked or Ate it … the belief that someone is talking to them saying people around them are doing things to hurt them on purpose, Even they talk about how people or something is always out to get them in some kind of way.
So Yes I’m Glad You Did the research and found this to be a True Problem
NOW HOW ABOUT MAKING THC SELLERS and GROWERS RESPONSIBLE FOR TREATMENT????? HOW LONG BEFORE THEY GET HELP??? HOW LONG IS LONG ENOUGH??
The vendors of cannabis will eventually be required to post warnings of possible side effects on their packaging. And, like the warnings on tobacco products, users will ignore them.
Since the “legalization” of medical cannabis in California in 1996, and many other states over the next decade, we have had MILLIONS of patients using regularly, under medical supervision, not to mention the millions more who have been using legally UNsupervised for nearly a decade, there is only one question we have to ask about cannabis and psychosis:
Why hasn’t the increased (TENS of MILLIONS) numbers of users resulted in a change in the epidemiology of cannabis-“linked” psychoses increased as well?
Perhaps the greatest cause of mental illness concerning the use of cannabis was the CONSTANT FEAR of being arrested and stigmatized. If we consider the numbers and the epidemiology, we actually see that LEGAL cannabis drastically reduces the risk of mental illness in users… or else we have been greatly underestimating the number of users for DECADES.