Researchers at the University of California San Diego School of Medicine, working with the genetic testing company 23andMe, have pinpointed regions of the human genome linked to cannabis use. Their discoveries reveal new genetic connections to psychiatric, cognitive, and physical health, offering insights that could eventually guide prevention and treatment strategies for cannabis use disorder. The findings were published on October 13, 2025, in Molecular Psychiatry.
“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 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 go on to develop cannabis use disorder, some studies estimate that nearly 30% will,” said Sanchez-Roige. “Understanding the genetics of early-stage behaviors may help clarify who is at greater risk, opening the door to prevention and intervention strategies.”
To explore these connections, the researchers performed a genome-wide association study (GWAS) using genetic data from 131,895 23andMe research participants. Participants completed surveys about whether they had ever used cannabis, and those who had were asked about their frequency of use.
“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 and co-author of the study. “Genetic tools like GWAS help us identify the molecular systems that connect 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. Earlier research has tied CADM2 to traits such as impulsivity, obesity, and cancer metastasis. This same gene was also linked to how often people use cannabis.
The second gene, Metabotropic Glutamate Receptor 3 (GRM3), influences how neurons communicate and how the brain adapts over time. GRM3 has previously been connected to psychiatric disorders including schizophrenia and bipolar disorder.
“We showed that the genetics of cannabis use — both trying it and using it more often — are tied to the genetics of other psychiatric traits, cognitive measures, and even physical health problems,” said Sanchez-Roige.
A secondary analysis revealed an additional 40 genes associated with lifetime cannabis use and four genes associated with frequency of cannabis use. Twenty-nine of these genes had not previously been associated with cannabis-related traits.
The researchers then analyzed which health conditions were correlated with a genetic predisposition for cannabis use. They analyzed thousands of traits in two large independent datasets from the National Institutes of Health’s (NIH) All of Us Research Program and Vanderbilt University Medical Center’s 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 and depression), cognitive traits (e.g., executive function and risk-taking) and physical health (e.g., diabetes, chronic pain and coronary artery disease). They were also associated with an increased risk for tobacco use, infectious diseases including HIV and viral hepatitis, and autoimmune diseases.
The study is one of the first genome-wide association studies to examine behaviors that precede cannabis use disorder.
“Cannabis use exists on a continuum,” said first author Hayley Thorpe, Ph.D., a visiting scholar in Sanchez-Roige’s lab and postdoctoral researcher at Western University. “By studying these intermediate traits, we can begin to map how genetic risk unfolds before cannabis use disorder develops.”
There are currently no FDA-approved drug therapies to treat cannabis use disorder. The authors hope that the biological discoveries generated by GWAS will support future efforts to identify therapeutic targets and preventative interventions against the disorder.
Additional co-authors on the study include: John J. Meredith, Mariela V. Jennings, Renata B. Cupertino, Shreya Pakala, UC San Diego; Pierre Fontanillas, Sarah L. Elson and the 23andMe Research Team at 23andMe, Inc.; Jibran Y. Khokhar, Western University; Emma C. Johnson, Washington University in St. Louis; and Lea K. Davis, Vanderbilt University Medical Center.
The study was funded, in part, by the National Institutes of Institute on Drug Abuse (grants R01 DA050721, P50DA037844 and P30DA060810) at the NIH, and the Tobacco-Related Disease Research Program (grant T32IR5226).
The 23andMe Research participants provided informed consent and volunteered to participate in the research online, under a protocol approved by the Association for Accreditation of Human Research Protection Programs, Inc. (AAHRPP)-accredited Salus IRB.
