Frequent use of high-potency cannabis can leave specific marks on DNA, especially on genes related to energy production and immune system function. Researchers have found that a DNA modification called methylation varies between frequent users who have experienced psychosis and those who have not, suggesting a possible genetic link to the risk of developing psychosis. This finding may eventually lead to blood tests that identify cannabis users who are more vulnerable to psychosis, helping to inform preventive approaches.
The rise in cannabis use in many parts of the world, especially of high-potency varieties (with 10% or more THC, the main psychoactive component), has led scientists to focus on its impact on mental health, particularly psychotic disorders.
Evidence shows that long-term cannabis use, starting in adolescence and at high doses, is associated with a higher risk of psychosis, with a 2- to 5-fold increase in the odds of developing the condition compared to non-users.
While the effects of cannabis on mental health are well established, the exact mechanisms of how it impacts brain function are complex and still being unraveled. One current focus is DNA methylation, an epigenetic process that alters gene expression without changing its structure.
This means that external factors, such as cannabis use, can “turn on” or “off” certain genes, directly affecting their function. This epigenetic mechanism has been extensively studied about smoking, but cannabis research is still in its early stages.
Existing studies suggest that cannabis use may affect genes involved in brain development, such as those related to the transmission of dopamine (a chemical crucial for controlling mood and behavior), and others associated with the endocannabinoid system (responsible for regulating several brain functions).
In addition, cannabis may influence “epigenetic age,” a measure of a person’s biological age based on changes in DNA. Frequent cannabis users may show signs of accelerated biological aging, which could increase the risk of several diseases.
This groundbreaking study, published in the journal Molecular Psychiatry by researchers at Washington University, was the first to show that high-potency cannabis use can alter the methylation of genes related to immune and mitochondrial function, which are systems essential for the body’s functioning and response to infections.
When comparing frequent cannabis users who experienced episodes of psychosis with those who did not develop the condition, the researchers noted significant differences in epigenetic markers between the two groups. This suggests that cannabis use may influence genetic vulnerability to psychosis, a serious mental disorder.
The study involved 682 participants (188 current cannabis users and 494 never users), including 239 people who had previously experienced a first episode of psychosis (FEP). They analyzed DNA samples from the participants’ blood, observing how methylation varied.
A specific site in the CAVIN1 gene was identified as differentially methylated in cannabis users, independent of other factors such as tobacco use. This indicates that frequent use of the drug may cause permanent changes in certain genes.
In addition, epigenetic changes were more pronounced in high-potency cannabis users, suggesting that higher doses of THC have a stronger impact. This raises the possibility that blood tests could be developed in the future to identify those most at risk of developing psychosis after using the substance, facilitating the creation of prevention strategies.
These findings are important as they show how cannabis use can alter key biological processes, bridging the gap between our genetics and environmental factors such as substance use. With cannabis use becoming increasingly common, especially among young people, understanding its effects on the body and brain is crucial to ensuring the mental health of the population.
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Methylomic signature of current cannabis use in two first-episode psychosis cohorts.
Dempster EL, Wong CCY, Burrage J et al.
Mol Psychiatry (2024). https://doi.org/10.1038/s41380-024-02689-0
Abstract:
The rising prevalence and legalization of cannabis worldwide have underscored the need for a comprehensive understanding of its biological impact, particularly on mental health. Epigenetic mechanisms, specifically DNA methylation, have gained increasing recognition as vital factors in the interplay between risk factors and mental health. This study aimed to explore the effects of current cannabis use and high-potency cannabis on DNA methylation in two independent cohorts of individuals experiencing first-episode psychosis (FEP) compared to control subjects. The combined sample consisted of 682 participants (188 current cannabis users and 494 never users). DNA methylation profiles were generated on blood-derived DNA samples using the Illumina DNA methylation array platform. A meta-analysis across cohorts identified one CpG site (cg11669285) in the CAVIN1 gene that showed differential methylation with current cannabis use, surpassing the array-wide significance threshold, and independent of the tobacco-related epigenetic signature. Furthermore, a CpG site localized in the MCU gene (cg11669285) achieved array-wide significance in an analysis of the effect of high-potency (THC = > 10%) current cannabis use. Pathway and regional analyses identified cannabis-related epigenetic variation proximal to genes linked to immune and mitochondrial function, both of which are known to be influenced by cannabinoids. Interestingly, a model including an interaction term between cannabis use and FEP status identified two sites that were significantly associated with current cannabis use with a nominally significant interaction suggesting that FEP status might moderate how cannabis use affects DNA methylation. Overall, these findings contribute to our understanding of the epigenetic impact of current cannabis use and highlight potential molecular pathways affected by cannabis exposure.
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