People who regularly use cannabis increase their risk of developing psychosis, whether or not they are genetically predisposed to the condition, researchers suggest.
A study by King’s College London (KCL) and South London and Maudsley NHS Foundation Trust shows the genetic load for schizophrenia and frequent use of cannabis independently contribute to the risk of psychosis, with each factor increasing the chances of psychosis even if the other factor is absent.
The findings, published in Psychological Medicine, provide insights to identify those at higher risk of psychosis and could help inform preventative strategies.
Previous research describes a well-established link between cannabis use and psychosis, but the influence of underlying genetics remains unclear. Using data from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) and UK Biobank, the researchers examined both the independent and combined impacts of heavy cannabis use and schizophrenia polygenic risk score (PRS) on the risk of developing psychosis. The PRS quantifies the likelihood that common genetic variants contribute to the risk of developing a disease or disorder.
The two data cohorts provided information on genetics, self-reported cannabis use and diagnoses of psychosis, and the researchers analysed information from 1,592 participants in the EU-GEI and 145,244 in the UK Biobank.
The findings indicate that PRS and cannabis use can both independently increase the risk of psychosis.
Among the EU-GEI cohort, the risk of developing psychosis was not correlated with cannabis use in people diagnosed with psychosis or in the control group (participants without a psychosis diagnosis). However, in the UK Biobank cohort, there was an increased risk of developing psychosis in the control group independent of their genetic disposition if cannabis was used daily or over a lifetime. The effect decreased significantly when accounting for cannabis use disorder (CUD), suggesting shared genetic factors predispose people to develop CUD rather than schizophrenia PRS being directly linked to cannabis use.
Dr Edoardo Spinazzola, from KCL and Consultant Adult Psychiatrist at South London and Maudsley NHS Foundation Trust, said: ‘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.’
The researchers also highlight the increased risks of sustained use of high-potency cannabis (delta-9 tetrahydrocannabinol (THC) content of 10 per cent or more).
Dr Spinazzola added: ‘Through further analysis of cannabis use of different frequencies and potencies, we have shown that the highest risk for psychosis is in those with greater genetic predisposition to schizophrenia who use high potency cannabis daily.’
The findings also indicate that the PRS for schizophrenia could become helpful in identifying those at risk for psychosis among less frequent users, enabling early preventative measures to be put in place.
Article reference: Psychological Medicine, First View, pp. 1 – 13. DOI: https://doi.org/10.1017/S0033291724002058
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