Genes Reveal Hidden Links Between Cannabis Use and Mental Health

The human genome still keeps secrets about why some people light up and others walk away. A massive genetic study from the University of California San Diego and 23andMe has traced cannabis use to specific genes tied not only to brain chemistry, but also to psychiatric, cognitive, and physical health. The findings, published in Molecular Psychiatry, mark one of the largest and most detailed investigations of cannabis-related behavior to date.

The research analyzed data from 131,895 participants who had shared genetic information and answered questions about whether and how often they used cannabis. The team then searched millions of DNA markers for patterns that tracked with lifetime use and frequency. What emerged was a genetic portrait connecting cannabis to everything from impulsivity and mental illness to metabolic disease.

Two Genes, Many Connections

The team identified two major genes at the center of the story. The first, CADM2, helps neurons form and communicate in the brain. It has appeared before in studies of impulsivity, obesity, and even cancer spread. The second, GRM3, influences how neurons exchange messages through glutamate, a key neurotransmitter for learning and memory. GRM3 variants have been linked to schizophrenia and bipolar disorder, giving the gene a familiar yet troubling profile in psychiatric genetics.

“Cannabis is widely used, but its long-term effects on health remain poorly characterized,” said Sandra Sanchez-Roige, Ph.D., associate professor of psychiatry at UC San Diego School of Medicine and senior author of the study.

The study did more than find individual genes. It also showed that lifetime and frequent cannabis use share deep genetic overlap with over 100 traits. These ranged from ADHD, anxiety, and depression to diabetes, chronic pain, and coronary artery disease. People with a stronger genetic tendency to use cannabis were also more likely to carry markers associated with tobacco use, viral infections such as HIV, and autoimmune disorders.

In total, the analysis uncovered 40 additional genes associated with lifetime use and four tied to frequency. Twenty-nine of them had never before been connected to cannabis behavior. The results suggest that cannabis use does not exist in genetic isolation, but sits within a web of biological systems that affect both brain and body.

Tracing Risk Before Addiction

By looking at people who had tried or regularly used cannabis but not necessarily developed dependence, the study mapped genetic risk earlier in the pathway to addiction. That approach could help researchers identify prevention targets long before cannabis use disorder appears.

“We’ve known for decades that genetic factors influence whether or not people will try drugs, how frequently they use those drugs, and the risk that they will become addicted to them,” said Abraham A. Palmer, Ph.D., professor and vice chair for basic research in the Department of Psychiatry at UC San Diego School of Medicine. “Genetic tools like GWAS help us identify the molecular systems that connect cannabis use to brain function and behavior.”

The researchers used two independent biobank datasets from the National Institutes of Health’s All of Us Research Program and Vanderbilt University Medical Center to check their findings. The genetic fingerprints of cannabis use remained consistent, reinforcing the link between early-stage behaviors and health outcomes later in life. These pre-addiction genetic markers may reveal which biological pathways could be adjusted through medication or behavioral intervention to reduce risk.

For now, cannabis use disorder remains without any FDA-approved drug therapy. The team hopes that a clearer genetic map could lead to new therapeutic targets or strategies for prevention. As cannabis becomes more widely accessible across the globe, such insights may prove essential for balancing its potential benefits with the risks embedded in our DNA.

Molecular Psychiatry: 10.1038/s41380-025-03219-2