Cannabis Use Leaves a Lasting Mark on the Epigenome

With the rising prevalence and legalization of cannabis worldwide, understanding its biological impact—especially on mental health—has become increasingly urgent. Research indicates that heavy use of high-potency cannabis significantly heightens the risk of mental health disorders. Factors such as starting at a young age and daily consumption further exacerbate this risk, underscoring the need for greater awareness of the potential consequences of cannabis use.

Recent research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London and the University of Exeter shows that frequent use of high-potency cannabis—defined as having a Delta-9-tetrahydrocannabinol (THC) content of 10% or more—leaves a unique molecular signature on DNA. This comprehensive analysis, published in the journal Molecular Psychiatry, links the use of high-potency cannabis to changes in DNA methylation, a key epigenetic mechanism.

Epigenetics involves heritable changes in gene expression that do not alter the underlying DNA sequence. These changes are driven by factors such as DNA methylation, histone modifications, and non-coding RNA interactions, playing a crucial role in how environmental and lifestyle factors shape health outcomes. As such, they are important targets for potential interventions in mental health disorders.

In earlier blog posts, we have discussed how THC can affect DNA methylation, lowering sperm count, and how daily cannabis exposure alters epigenetic changes crucial for fetal development. This study’s focus on DNA methylation related to high-potency cannabis use expands our understanding of how cannabis may influence genes linked to immune and mitochondrial function, potentially contributing to the development of psychosis.

The research examined a diverse cohort of 682 participants, including individuals experiencing their first episode of psychosis (FEP) and those without a history of psychotic experiences. Key findings revealed that frequent users of high-potency cannabis exhibit significant alterations in DNA methylation patterns. Notably, genes associated with mitochondrial function and immune response were particularly affected, with the CAVIN1 gene—important for cellular energy regulation—showing hypomethylation. Understanding the implications of these findings is critical, as they suggest that high-potency cannabis may contribute to an increased risk of developing mental health issues, including psychosis. Senior author Marta Di Forti emphasized the urgency of these insights, stating, “With the increasing prevalence of cannabis use, particularly high-potency types, it’s vital to comprehend their biological impacts on mental health.”

The study also uncovered important distinctions based on FEP status, suggesting that the effects of cannabis on DNA methylation may vary significantly between individuals with and without a history of psychosis. This variance opens avenues for further research into how these epigenetic changes may serve as biomarkers for identifying individuals at higher risk of psychosis due to cannabis use, potentially paving the way for preventive measures.

Prior studies have emphasized the complex interplay between substance use and mental health, especially regarding epigenetic modifications. This current research builds on that foundation, revealing how high-potency cannabis can alter gene activity and potentially influence long-term mental health outcomes. Dr. Emma Dempster, the study’s first author, noted, “This study is the first 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.”

This research emphasizes how lifestyle choices, such as cannabis use, shape the epigenetic landscape, particularly among vulnerable groups. With over 60% of participants using potent cannabis products from age 16, the findings also highlight the need for further studies on its impact on mental health. Di Forti noted, “Future research should explore if the DNA signature of high-potency cannabis use can help identify those at risk of developing psychosis in both recreational and medicinal contexts.”

Understanding the DNA methylation patterns linked to high-potency cannabis is crucial for addressing long-term mental health risks. As THC consumption rises, recognizing its epigenetic effects may inform new therapeutic approaches and strategies for preventing disorders in at-risk populations.

Source: Dempster, E.L., Wong, C.C.Y., Burrage, J. et al. Methylomic signature of current cannabis use in two first-episode psychosis cohorts. Mol Psychiatry (16 October 2024).

Resource: King’s College London. High potency cannabis use leaves unique signature on DNA, study shows. 16 October 2024.

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