As cannabis use becomes more common worldwide, researchers are eager to understand its effects beyond the obvious. A recent study published in molecular psychiatry, Nature, examines how cannabis affects gene expression through changes in DNA methylation. Emma L. Dempster and colleagues lead this study, delving into how cannabis use may alter genetic markers, potentially impacting mental health, particularly for those experiencing first-episode psychosis (FEP). Their findings could reshape how we understand the biological impact of cannabis, especially its connection to psychotic disorders.
The legal status of cannabis is changing in many countries, with increased recreational and medicinal use. However, cannabis isn’t harmless for everyone. There has been growing concern about its link to psychosis, particularly in young people using high-potency strains. While several studies have connected cannabis to mental health risks, the biological mechanisms behind this link are still unclear. The research is delved into this gap by examining the “methylomic signature” of cannabis use, which refers to the chemical marks cannabis leaves on our DNA, akin to highlights in a book, and its ability to activate or deactivate certain genes.
They focused on two groups of participants: those with first-episode psychosis and those without, comparing 188 current cannabis users to 494 people who have never used cannabis. Researchers recruited the participants from various sites across Europe, incorporating both clinical assessments and genetic analysis to offer a comprehensive understanding of the impact of cannabis use on gene expression. Researchers collected DNA samples from blood and analyzed them using advanced tools like the Illumina DNA methylation array platform, which can examine over 450,000 methylation sites across the genome. This level of detail allowed for a thorough exploration of the epigenetic changes associated with cannabis use. This allowed them to detect small changes in the methylation patterns, which are the chemical tags that help control gene expression.
One of the key findings was the identification of significant changes in two particular genes, CAVIN1 and MCU, among cannabis users. The mitochondrial health, crucial for energy production in cells, is associated with the CAVIN1 gene. Healthy mitochondrial function is particularly important for mental health because the brain requires a significant amount of energy to maintain proper function, including supporting neurotransmitter activity and overall cognitive processes. Changes in this gene might help explain why heavy cannabis use is associated with mental health issues, given that healthy mitochondrial function is crucial for brain activity. The MCU gene, involved in calcium transport within cells, also showed alterations related to high-potency cannabis use, hinting at disruptions in cellular health that could have broader implications for mental function.
“Our findings point to cannabis use affecting mitochondrial function, which could be key to understanding its role in psychosis,” lead researcher Emma L. Dempster explained. Mitochondria are the powerhouses of the cell, and any disruption to their function could have widespread consequences for brain health, especially in individuals already predisposed to mental health conditions. “These alterations in gene regulation offer fresh perspectives on the biological foundations of cannabis’ influence on mental health.”
The researchers found that cannabis users with first-episode psychosis had more significant DNA changes compared to cannabis users without psychosis. This suggests that people already vulnerable to mental health disorders might be more susceptible to the epigenetic effects of cannabis, further increasing their risk.
This research could have far-reaching implications. For healthcare professionals, understanding how cannabis interacts with the human genome offers a new angle on prevention and treatment, particularly in terms of early identification of at-risk individuals and tailored interventions based on genetic susceptibility. We could more precisely target interventions if certain genetic markers or methylation changes can predict which individuals are more vulnerable to cannabis-induced psychosis. This is particularly crucial for young people, who are more likely to experiment with cannabis and whose brains are still developing.
Co-author Edoardo Spinazzola added, “By identifying specific changes in the DNA of cannabis users, especially those experiencing early signs of psychosis, we hope to provide a scientific basis for targeted public health strategies. We must comprehend that cannabis does not affect everyone equally—for some, the risks are significantly higher.”
For more information, visit: https://doi.org/10.1038/s41380-024-02689-0
