Warning: Marijuana Use May Alter Your DNA Methylation

A study by Northwestern Medicine links recent and long-term marijuana use to changes in the human epigenome. The research identified significant epigenetic changes through observing DNA methylation markers. While the study does not establish causal relationships, it sets the stage for further research into marijuana’s epigenetic impact and its potential health effects.

Recent and long-term marijuana use is linked to changes in the human epigenome, a new Northwestern Medicine study published in the journal Molecular Psychiatry has found.

Marijuana ranks as the most widely used drug in the United States. Data from the Centers for Disease Control and Prevention (CDC) indicates that approximately 48.2 million people, which constitutes around 18% of all Americans, had used marijuana at least once in 2019. This is the most recent year for which data is available.

Despite its prevalent use and legalization in several states, the health consequences of marijuana use are not well understood, according to Lifang Hou, MD, PhD, chief of Cancer Epidemiology and Prevention in the Department of Preventive Medicine and senior author of the study.

Drew Nannini, DO, PhD, a postdoctoral fellow in the Hou lab, was first author of the study published in Molecular Psychiatry. Credit: Northwestern Medicine

“Despite its growing popularity, as well as recent legalization by several states, the effect of marijuana on epigenetic factors has not been well studied,” said Hou, who is also Director of the Center for Global Oncology in the Robert J. Havey, MD, Institute for Global Health. “We previously identified associations between marijuana use and the aging process as captured through DNA methylation. We wanted to further explore whether specific epigenetic factors were associated with marijuana and whether these factors are related to health outcomes.”

In the study, investigators analyzed whole blood samples taken five years apart from people who previously participated in the Coronary Artery Risk Development in Young Adults (CARDIA) study. The current study included data from more than 900 adults.

The scientists surveyed each participant for recent marijuana use and estimated cumulative use and then performed DNA methylation profiling on their blood samples to reveal epigenetic changes associated with marijuana use.

By studying changes in DNA methylation, the biological process by which methyl groups are added to DNA molecules, thereby altering gene expression, scientists were able to link marijuana use to changes in the human epigenome.

Overall, investigators observed 22 and 31 DNA methylation markers associated with recent and cumulative marijuana use, respectively, from the first samples and 132 and 16 methylation markers in the second batch of samples, according to the study.

Many of the epigenetic changes were found in pathways previously linked to cellular proliferation, hormone signaling, infections, and mental health disorders such as schizophrenia, bipolar disorder, and substance use disorders, Hou said.

Lifang Hou, MD, PhD, chief of Cancer Epidemiology and Prevention in the Department of Preventive Medicine, was senior author of the study published in Molecular Psychiatry. Credit: Northwestern Medicine

“In our study, we observed associations between cumulative marijuana use and multiple epigenetic markers across time,” Hou said. “Interestingly, we consistently identified one marker that has previously been associated with tobacco use, suggesting a potential shared epigenetic regulation between tobacco and marijuana use. The observed marijuana markers were also associated with cell proliferation, infection, and psychiatric disorders, however, additional studies are needed to replicate and verify these findings.”

While the study does not establish a causal relationship between marijuana use and epigenetic changes, nor between those epigenetic changes and observed health outcomes, the findings may be useful in future research into the epigenetic effects of marijuana use, said Drew Nannini, DO, PhD, a postdoctoral fellow in the Hou lab and first author of the study.

“This research has provided novel insights into the association between marijuana use and epigenetic factors,” Nannini said. “Additional studies are needed to determine whether these associations are consistently observed in different populations. Moreover, studies examining the effect of marijuana on age-related health outcomes may provide further insight into the long-term effect of marijuana on health.”

Reference: “Genome-wide DNA methylation association study of recent and cumulative marijuana use in middle aged adults” by Drew R. Nannini, Yinan Zheng, Brian T. Joyce, Kyeezu Kim, Tao Gao, Jun Wang, David R. Jacobs, Pamela J. Schreiner, Kristine Yaffe, Philip Greenland, Donald M. Lloyd-Jones and Lifang Hou, 31 May 2023, Molecular Psychiatry.
DOI: 10.1038/s41380-023-02106-y

The study was supported by the National Heart, Lung, and Blood Institute in collaboration with Kaiser Foundation Research Institute and Northwestern University. Additional funding was provided by American Heart Association grants 14SFRN20790000 and 17SFRN33700278, and National Institute on Aging grants R21AG063370, R21AG068955, R01AG081244 and R01AG069120.