Summary: Researchers analyzing data from over 130,000 participants have identified specific genes associated with cannabis use and its frequency, revealing strong links to psychiatric, cognitive, and physical health traits. The genes CADM2 and GRM3, already known for roles in brain communication and impulsivity, appear central to how individuals initiate and sustain cannabis use.
The study also uncovered dozens of other genes tied to risk-taking, schizophrenia, and chronic illnesses such as diabetes and coronary artery disease. These findings could lead to new prevention strategies and potential therapeutic targets for cannabis use disorder, which currently has no approved drug treatments.
Key Facts:
- Two Key Genes: Cannabis use is linked to CADM2 and GRM3, genes involved in brain signaling and impulsivity.
- Broader Health Impact: Genetic predisposition for cannabis use overlaps with over 100 psychiatric, cognitive, and physical traits.
- Preventive Potential: Findings could inform personalized strategies to predict and prevent cannabis use disorder.
Source: UCSD
University of California San Diego of Medicine researchers, in collaboration with the genetic testing company 23andMe, have identified regions of the human genome associated with cannabis use, uncovering new relationships with psychiatric, cognitive and physical health.
The findings may inform the development of prevention and treatment strategies for cannabis use disorder.
The study was 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.”
The research team conducted a genome-wide association study (GWAS) analyzing relationships between cannabis use and genetic data provided by 131,895 23andMe research participants. They answered survey questions about whether or not they had ever used cannabis, and those who answered yes were also asked how frequently they used the drug.
“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 found that lifetime cannabis use was associated with two genes. The first was Cell Adhesion Molecule 2 (CADM2), a gene involved in cell assembly and in signaling between nerve cells, particularly in the brain.
Previous studies have linked CADM2 to various traits and conditions, including impulsive personality, obesity and cancer metastasis. Frequency of cannabis use was also found to be associated with the CADM2 gene.
The second gene was Metabotropic Glutamate Receptor 3 (GRM3), which is involved in communication between neurons and long-term brain plasticity. GRM3 has already been linked 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.
Funding: 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.
Key Questions Answered:
A: Two major genes—CADM2, associated with impulsivity, and GRM3, linked to brain plasticity—show strong associations with both lifetime and frequent cannabis use.
A: Genetic overlaps were found between cannabis use and conditions such as schizophrenia, anxiety, chronic pain, and diabetes, indicating shared biological pathways.
A: Understanding genetic risk factors can help identify individuals at higher risk early, supporting targeted prevention and guiding future drug development.
About this genetics, cannabis use disorder, and mental health research news
Author: Susanne Bard
Source: UCSD
Contact: Susanne Bard – UCSD
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Genome-wide association studies of lifetime and frequency of cannabis use in 131,895 individuals” by Sandra Sanchez-Roige et al. Molecular Psychiatry
Abstract
Genome-wide association studies of lifetime and frequency of cannabis use in 131,895 individuals
Cannabis is one of the most widely used drugs globally. We performed genome-wide association studies (GWASs) of lifetime (N = 131,895) and frequency (N = 73,374) of cannabis use.
For lifetime cannabis use, we identified two loci, one near CADM2 (rs35827242, p = 4.63E-12) and another near GRM3 (rs12673181, p = 6.90E-09). For frequency of cannabis use, we identified one locus near CADM2 (rs4856591, p = 8.10E-09; r2 = 0.76 with rs35827242).
Lifetime and frequency of cannabis use were heritable (12.88 vs. 6.63%) and genetically correlated with previous GWASs of lifetime use and cannabis use disorder (CUD), as well as other substance use and cognitive traits.
Polygenic scores (PGSs) for lifetime and frequency of cannabis use predicted cannabis use phenotypes in All of Us participants.
A phenome-wide association study using a PGS for lifetime cannabis use to interrogate a hospital cohort replicated prior associations with substance use and mood disorders, and uncovered novel associations with celiac and infectious diseases.
This work demonstrates the utility of pre-addiction phenotypes in cannabis use genomic discovery.
