Researchers at the University of California, San Diego School of Medicine, in collaboration with genetic testing company 23andMe, have identified regions of the human genome associated with cannabis use. Their findings reveal new genetic relationships with psychiatric, cognitive, and physical health, providing insights that may ultimately guide prevention and treatment strategies for cannabis use disorders. The findings of this study were published on October 13, 2025. Molecular psychiatry.
"Although cannabis is widely used, its long-term health effects are still poorly understood," said Sandra Sánchez Roij, Ph.D., associate professor of psychiatry at the University of California San Diego School of Medicine and senior author of the study. The researchers were also interested in the relationship between genetics and traits that contribute to the development of cannabis use disorder, which can interfere with a person's daily life.
"While most people who try cannabis do not develop cannabis use disorder, some studies estimate that as many as 30% will develop cannabis use disorder," Sánchez-Roijs said. "Understanding the genetics of early-stage behaviors can help reveal who is at greater risk and open the door to prevention and intervention strategies."
To investigate these associations, researchers performed a genome-wide association study (GWAS) using genetic data from 131,895 23andMe study participants. Participants completed a questionnaire asking whether they had ever used cannabis, and those who had used it were asked how often they used it.
"We've known for decades that genetic factors influence whether people try drugs, how often they use them, and their risk of becoming addicted to them," said Abraham A. Palmer, Ph.D., professor and associate director of basic research in the department of psychiatry at the University of California, San Diego School of Medicine and co-author of the study. "Genetic tools like GWAS can help identify molecular systems that link cannabis use to brain function and behavior."
The study identified two genes significantly associated with lifetime cannabis use. The first, cell adhesion molecule 2 (CADM2), plays a role in how nerve cells form connections and communicate in the brain. Previous studies have linked CADM2 to traits such as impulsivity, obesity, and cancer metastasis. This same gene was also associated with how often people used cannabis.
The second gene, metabotropic glutamate receptor 3 (GRM3), which affects how neurons communicate and how the brain adapts over time. GRM3 has previously been associated with psychiatric disorders such as schizophrenia and bipolar disorder.
"We showed that the genetics of cannabis use (both trying and using more frequently) are linked to the genetics of other psychiatric traits, cognitive function, and even physical health problems," Sánchez-Roige said.
Secondary analyzes revealed an additional 40 genes associated with lifetime cannabis use and 4 genes associated with frequency of cannabis use. 29 of these genes have not previously been associated with cannabis-related traits.
The researchers then analyzed which health conditions were correlated with a genetic predisposition to cannabis use. They analyzed thousands of traits in two large, independent datasets from the National Institutes of Health (NIH). Research programs for all of us Vanderbilt University Medical Center Biobank.
Across the genome, lifetime cannabis use and frequency of cannabis use were genetically correlated with more than 100 different traits, including psychiatric conditions (e.g., schizophrenia, ADHD, anxiety, depression), cognitive traits (e.g., executive function, risk-taking), and physical health (e.g., diabetes, chronic pain, coronary artery disease). It was also associated with increased risk of smoking, infections such as HIV and viral hepatitis, and autoimmune diseases.
This study is one of the first genome-wide association studies investigating behaviors that precede cannabis use disorder.
"Cannabis use continues to exist," said lead author Dr. Hayley Thorpe, a visiting scholar in the Sánchez-Roige lab and a postdoctoral fellow at Western University. "By studying these intermediate traits, we can begin to map how genetic risk evolves before cannabis use disorder develops."
There are currently no FDA-approved medications to treat cannabis use disorder. The authors hope that the biological discoveries generated by GWAS will support future efforts to identify therapeutic targets and preventive interventions for this disease.
Other co-authors on the study include John J. Meredith, Mariela V. Jennings, Renata B. Cupertino, and Shreya Pakala, University of California, San Diego; Pierre Fontanillas, Sarah L. Elson, and the 23andMe Research Team at 23andMe, Inc. Gibran Y. Khokhar, Western University. Emma C. Johnson, Washington University in St. Louis; Lea K. Davis of Vanderbilt University Medical Center;
This study was funded in part by the NIH's National Institute on Drug Abuse (grants R01 DA050721, P50DA037844 and P30DA060810) and the Tobacco-Related Disease Research Program (grant T32IR5226).
Participants in 23andMe Research provided informed consent and volunteered to participate in the study online under a protocol approved by the Association for the Accreditation of Human Research Protection Programs (AAHRPP)-accredited Salus IRB.