Prolonged consumption of cannabis at +10% THC leaves a unique signature on DNA

A study published in Molecular Psychiatry suggests that consumption of high-THC cannabis, defined as having a THC content greater than 10%, leaves a distinct mark on DNA.

Research also shows that the effect of cannabis use on DNA is different in people who know their first episode of psychosis compared with users who have never experienced psychosis, suggesting that DNA blood tests could help characterize cannabis users at risk of developing psychosis to inform preventive approaches.

Marta Di Forti, lead author of the study and Professor of Drugs, Genes and Psychosis at King's IoPPN, said, «Given the growing prevalence of cannabis use and the increasing availability of high-potency cannabis, there is an urgent need to better understand its biological impact, particularly on mental health.»

«Our study is the first to show that high-potency cannabis leaves a unique signature on DNA, linked to immune system mechanisms and energy production. Future research should examine whether the DNA signature of current cannabis use, and in particular that of high-potency types of cannabis, can help identify users most at risk of developing psychosis, whether through recreational or medicinal use.».

The researchers studied the effects of cannabis use on DNA methylation, a chemical process detected in blood samples that alters the way genes function (whether they are switched on or off).

DNA methylation is a type of epigenetic change, meaning that it alters gene expression without affecting the DNA sequence itself, and is considered a key factor in the interaction between risk factors and mental health.

The team from the laboratory at the University of Exeter, UK, carried out complex genome-wide DNA methylation analyses on blood samples taken from people who had experienced a first episode of psychosis and those who had never had a psychotic experience. The researchers studied the impact of current cannabis use, including frequency and potency, on the DNA of 682 participants.

Analysis showed that frequent users of high-potency cannabis showed changes in genes related to mitochondrial and immune function, in particular the CAVIN1 gene, which may affect energy and immune response. These changes cannot be explained by the’tobacco's well-known impact on DNA methylation which causes more damage than cannabis.

Emma Dempster, Senior Lecturer at the University of Exeter and first author of the study, said, «This is the first study to show that frequent use of high-potency cannabis leaves a distinct molecular mark on DNA, affecting in particular genes related to energy and immune function.»

«Our results provide important insights into how cannabis use can alter biological processes. DNA methylation, the link between genetics and environmental factors, is a key mechanism that allows external influences, such as substance use, to affect gene activity. These epigenetic changes, shaped by lifestyle and exposures, offer valuable insight into how cannabis use can influence mental health through biological pathways.».

Emma Dempster meta-analyzed data from two cohorts: the GAP study of first-episode psychosis patients at the South London and Maudsley NHS Foundation Trust, and the EU-GEI study of first-episode psychosis patients and healthy controls in England, France, the Netherlands, Italy, Spain and Brazil.

A total of 239 participants suffering from a first episode of psychosis and 443 healthy controls representing the general population of the two study sites were provided with DNA samples.

Most of the cannabis users in the study used high-potency cannabis more than once a week (frequent use) and had first used cannabis at the age of 16, on average.

In July 2023, a study of 1,000 adults was already making the connection between cannabis use and epigenetic changes.