DNA changes from high potency cannabis use may signal psychosis risk

Published in Molecular Psychiatry, this is the first study to suggest that the use of high potency cannabis leaves a distinct mark on DNA, providing valuable insights into the biological impact of cannabis use. High potency cannabis is defined as having Delta-9-tetrahydrocannabinol (THC) content of 10 per cent or more. 

The research also showed the effect of cannabis use on DNA is different in people experiencing their first episode of psychosis compared to users who have never experienced psychosis, suggesting there could be potential for DNA blood tests to help characterise those cannabis users at risk of developing psychosis to inform preventative approaches. 

The study was funded by the Medical Research Council, the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre (BRC) and the NIHR Exeter BRC.

Senior author Marta Di Forti, Professor of Drugs, Genes and Psychosis at King's IoPPN said: "With the increasing prevalence of cannabis use and more availability of high potency cannabis, there is a pressing need to better understand its biological impact, particularly on mental health. Our study is the first to show high potency cannabis leaves a unique signature on DNA related to mechanisms around the immune system and energy production. Future research needs to explore if the DNA signature for current cannabis use, and in particular the one of high potency types, can help identify those users most at risk to develop psychosis, both in recreational and medicinal use settings."

Researchers explored the effects of cannabis use on DNA methylation – a chemical process detected in blood samples that alters how genes are functioning (whether they are switched 'on' or 'off'). DNA methylation is a type of epigenetic change, which means it alters gene expression without affecting the DNA sequence itself and is considered a vital factor in the interplay between risk factors and mental health.

The laboratory team at the University of Exeter conducted complex analyses of DNA methylation across the whole human genome using blood samples from both people who have experienced first-episode psychosis and those who have never had a psychotic experience. The researchers investigated the impact of current cannabis use, including frequency and potency, on DNA of a total of 682 participants

The analysis showed that frequent users of high-potency cannabis had changes in genes related to mitochondrial and immune function, particularly the CAVIN1 gene, which could affect energy and immune response. These changes were not explained by the well-established impact that tobacco has on DNA methylation, which is usually mixed into joints by most cannabis users.

This is the first study to show that frequent use of high-potency cannabis leaves a distinct molecular mark on DNA, particularly affecting genes related to energy and immune function. Our findings provide important insights into how cannabis use may alter biological processes. DNA methylation, which bridges the gap between genetics and environmental factors, is a key mechanism that allows external influences, such as substance use, to impact gene activity. These epigenetic changes, shaped by lifestyle and exposures, offer a valuable perspective on how cannabis use may influence mental health through biological pathways."

Dr. Emma Dempster, Senior Lecturer, University of Exeter and study's first author

Dr. Emma Dempster meta-analyzed data from two cohorts: the GAP study, which consists of patients with first episode psychosis in South London and Maudsley NHS Foundation Trust, and the EU-GEI study, which consists of patients with first episode psychosis and healthy controls across England, France, the Netherlands, Italy, Spain and Brazil. This totalled 239 participants with first episode psychosis and 443 healthy controls representing the general population from both studies sites who had available DNA samples.

Most of the cannabis users in the study used high-potency cannabis more than once a week (defined as frequent use) and had first used cannabis at age 16-years-old, on average. High potency cannabis was defined as having Delta-9-tetrahydrocannabinol (THC) content of 10 per cent or greater. THC is the principal psychoactive constituent in cannabis.