The study shows that frequent use of high-potency cannabis alters DNA, affecting genes related to energy and immune function. These changes differ between those with and without psychosis, suggesting cannabis use could influence mental health through biological pathways.
According to new research from the Institute of Psychiatry, Psychology & Neuroscience at King's College London and the University of Exeter, the use of high-potency cannabis leaves a unique imprint on DNA.
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 percent 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 characterize 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 that 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."
Research Focus on DNA Methylation
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 the DNA of a total of 682 participants
Key Findings on Gene Function
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.
Dr. Emma Dempster, Senior Lecturer at the University of Exeter and the study's first author, said: "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 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 totaled 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 percent or greater. THC is the principal psychoactive constituent in cannabis.
Reference: "Methylomic signature of current cannabis use in two first-episode psychosis cohorts" by Emma L. Dempster, Chloe C. Y. Wong, Joe Burrage, Eilis Hannon, Diego Quattrone, Giulia Trotta, Victoria Rodriguez, Luis Alameda, Edoardo Spinazzola, Giada Tripoli, Isabelle Austin-Zimmerman, Zhikun Li, Charlotte Gayer-Anderson, Tom P. Freeman, Emma C. Johnson, Hannah E. Jongsma, Simona Stilo, Caterina La Cascia, Laura Ferraro, Daniele La Barbera, Antonio Lasalvia, Sarah Tosato, Ilaria Tarricone, Giuseppe D'Andrea, Michela Galatolo, Andrea Tortelli, Maurizio Pompili, Jean-Paul Selten, Lieuwe de Haan, Paulo Rossi Menezes, Cristina M. Del Ben, Jose Luis Santos, Manuel Arrojo, Julio Bobes, Julio Sanjuán, Miguel Bernardo, Celso Arango, Peter B. Jones, Gerome Breen, Valeria Mondelli, Paola Dazzan, Conrad Iyegbe, Evangelos Vassos, Craig Morgan, Diptendu Mukherjee, Jim van Os, Bart Rutten, Michael C. O'Donovan, Pak Sham, Jonathan Mill, Robin Murray and Marta Di Forti, 16 October 2024, Molecular Psychiatry.
DOI: 10.1038/s41380-024-02689-0
Funding: Medical Research Council, NIHR Maudsley Biomedical Research Centre
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