High-Potency Cannabis Alters DNA, Linked to Psychosis Risk

Understanding Cannabis-Induced Psychosis

Cannabis, one of the most widely consumed substances around the world, continues to pose intriguing questions about its effects on the brain, particularly in relation to the unsettling issue of cannabis-induced psychosis.

Recent research offers insight into the biological consequences of using high-potency cannabis, revealing specific genetic alterations linked to its consumption. A study published in Molecular Psychiatry uncovers distinct changes in DNA associated with high-potency cannabis use.

The findings highlight critical differences in these genetic modifications between people encountering their first psychotic episode and those who have not faced this troubling condition.

This suggests a potential for monitoring DNA changes as a means to identify those at a greater risk of developing psychosis.

Rising Potency and Its Impact

Since the 1990s, cannabis potency has seen a dramatic increase, especially in the UK and US, where products containing up to 90% THC, the primary psychoactive compound in cannabis, are now accessible, particularly in states like Colorado where cannabis has been legalized.

THC, while just one of over 144 compounds found in cannabis, serves as the primary marker for its potency and effect. Numerous studies indicate that higher concentrations of THC are associated with stronger effects, with evidence showing that people who consume cannabis with a THC level of 10% or more daily are five times more likely to develop psychotic disorders compared to non-users.

The manifestations of these disorders can be distressing, including auditory hallucinations, delusions of persecution, and pervasive paranoia, which can severely impact quality of life.

Genetic Insights and Future Directions

The research sought to delve into the molecular consequences of cannabis consumption, concentrating on the distinctive features of high-potency varieties and their potential to identify those at increased risk for psychosis.

To explore this, the team examined DNA methylation—a biochemical process that modifies gene activity without changing the DNA sequence itself—within the framework of epigenetics.

This field studies how environmental factors and lifestyle choices, such as cannabis use, interact with our genetic makeup to influence both physical and mental health. While earlier studies have investigated the cumulative effects of cannabis use on DNA methylation, they often neglected the varying potencies and their implications for people experiencing psychosis.

The current study draws on data from two extensive case-control investigations: the Genetic and Psychosis Study in South London and the EU-GEI Study, which included participants from a variety of countries including England, France, the Netherlands, Italy, Spain, and Brazil.

In total, the research scrutinized 239 people encountering their first psychotic episode alongside 443 healthy controls, with a demographic composition roughly two-thirds male and ages ranging from 16 to 72.

Each participant provided details about their cannabis use along with blood samples for DNA analysis. Notably, about 38% of the participants reported using cannabis more than once a week, with high-potency varieties frequently consumed beginning around the age of 16.

The analysis of DNA methylation was thorough, focusing on various genomic regions while accounting for potential confounding factors like age, gender, ethnicity, and tobacco use. The results revealed that using high-potency cannabis distinctly modifies DNA methylation patterns, particularly affecting genes linked to energy metabolism and immune function.

While alterations were noted among all high-potency users, a unique pattern emerged in those who had experienced psychosis. These epigenetic changes illustrate how external influences, such as cannabis consumption, can affect gene functionality.

Importantly, these modifications could not be attributed to tobacco, which is often mixed with cannabis in joints and known to induce its own DNA methylation alterations. This finding emphasizes the potential role of epigenetic modifications as a bridge linking high-potency cannabis use to psychotic outcomes.

By examining these changes, researchers may better understand the biological mechanisms that heighten susceptibility to psychosis among cannabis users. The hope is that these findings will enrich the understanding of the biological effects of cannabis.

Future research should focus on whether the DNA methylation patterns associated with cannabis use could serve as biomarkers for identifying people at a higher risk of developing psychosis.

Such advancements could lead to more effective prevention strategies and help guide safer consumption practices.

Study Details:

• Title: High-potency cannabis leaves a distinct mark on DNA
• Authors: Marta Di Forti, Emma Dempster
• Journal: Molecular Psychiatry
• Publication Date: November 2024
• DOI: 10.1038/s41380-024-02689-0