Summary: Researchers who analyzed genetic data from more than 130,000 volunteers have pinpointed specific genes associated with trying cannabis and with how often people use it. The study highlights two genes—CADM2 and GRM3—that are central to brain signaling and impulse-related behaviors, and reveals broad genetic overlap between cannabis use and a range of psychiatric, cognitive, and physical health traits.
The research also identified dozens of additional genes linked to risk-taking behavior, schizophrenia and chronic illnesses such as diabetes and coronary artery disease. These discoveries may support the development of improved prevention strategies and point to potential therapeutic targets for cannabis use disorder, a condition that currently lacks FDA‑approved drug treatments.
Key Facts:
- Two principal genes: CADM2 and GRM3 are strongly associated with lifetime cannabis use and with frequency of use.
- Wider health connections: Genetic predisposition for cannabis use overlaps with more than 100 psychiatric, cognitive and physical traits.
- Prevention and treatment potential: Understanding genetic risk may enable earlier identification of people at risk and guide future prevention and treatment efforts for cannabis use disorder.
Source: UCSD
Researchers at the University of California San Diego School of Medicine, in collaboration with 23andMe, conducted a large genome-wide association study (GWAS) to map genetic regions associated with cannabis use and its frequency. Their analysis reveals new links between cannabis-related behaviors and psychiatric, cognitive and physical health measures.
The study was published on October 13, 2025 in Molecular Psychiatry.
“Cannabis is widely used, but its long-term effects on health remain incompletely understood,” said Sandra Sanchez‑Roige, Ph.D., associate professor of psychiatry at UC San Diego School of Medicine and senior author of the study. The team focused on genetic influences that contribute to behaviors leading up to cannabis use disorder, which can significantly disrupt daily life for some individuals.
“While most people who try cannabis do not develop cannabis use disorder, some estimates suggest nearly 30% of users may go on to problematic use,” Sanchez‑Roige added. “By understanding the genetics behind early-stage behaviors, we can better identify who is at greater risk and design targeted prevention strategies.”
The researchers performed a GWAS using genetic and survey data from 131,895 23andMe research participants. Participants reported whether they had ever used cannabis and, if so, how frequently they used the drug. Using these measures, the investigators compared genetic variants across the genome to find loci associated with lifetime use and with use frequency.
“Genetic factors influence whether people try drugs, how often they use them, and their risk of developing addiction,” 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 a co‑author of the study. “GWAS helps reveal the molecular systems that link cannabis use to brain function and behavior.”
The analysis identified two primary genes associated with lifetime cannabis use. The first, Cell Adhesion Molecule 2 (CADM2), plays a role in cell assembly and signaling between neurons, and has been previously connected to impulsivity, obesity and cancer metastasis. CADM2 was also associated with how frequently participants used cannabis. The second gene, Metabotropic Glutamate Receptor 3 (GRM3), supports neuronal communication and long‑term synaptic plasticity and has been implicated in psychiatric conditions such as schizophrenia and bipolar disorder.
Beyond CADM2 and GRM3, a secondary analysis revealed 40 additional genes associated with lifetime use and four genes associated with frequency of use; 29 of those genes had not previously been linked to cannabis-related traits. These discoveries expand the genomic landscape connecting cannabis behaviors to biological pathways.
To examine broader health implications, the researchers tested associations between genetic predisposition for cannabis use and thousands of health traits using two independent biobank datasets—the NIH All of Us Research Program and Vanderbilt University Medical Center’s biobank. They found genetic correlations between lifetime and frequent cannabis use and more than 100 traits, including psychiatric conditions (schizophrenia, ADHD, anxiety, depression), cognitive measures (executive function, risk-taking), and physical health problems (diabetes, chronic pain, coronary artery disease). Associations also emerged with higher risk of tobacco use, certain infectious diseases and autoimmune conditions.
This study is among the first GWAS efforts to focus on 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. “Studying these intermediate traits helps us map how genetic risk unfolds before a disorder develops.”
Because there are currently no FDA‑approved medications for cannabis use disorder, the authors emphasize that genetic discoveries from GWAS could guide future identification of therapeutic targets and inform preventive interventions tailored to those at elevated risk.
Additional co‑authors 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 (23andMe, Inc.); Jibran Y. Khokhar (Western University); Emma C. Johnson (Washington University in St. Louis); and Lea K. Davis (Vanderbilt University Medical Center).
Funding: This research received partial support from the National Institute on Drug Abuse (grants R01 DA050721, P50DA037844 and P30DA060810) and the Tobacco‑Related Disease Research Program (grant T32IR5226).
23andMe research participants provided informed consent and volunteered online under a protocol approved by an AAHRPP‑accredited institutional review board.
Key Questions Answered:
A: Two major genes—CADM2, which is associated with impulsivity and neuronal signaling, and GRM3, involved in synaptic communication and brain plasticity—show strong associations with lifetime cannabis use and with higher frequency of use.
A: Genetic overlap was observed between cannabis use and a wide range of traits, including psychiatric disorders (schizophrenia, ADHD, anxiety, depression), cognitive features (executive function, risk-taking), and physical conditions such as diabetes, chronic pain and coronary artery disease, suggesting shared biological pathways.
A: Identifying genetic risk factors for early-stage behaviors can help flag individuals at elevated risk before disorder onset, supporting targeted prevention efforts and informing future drug development for cannabis use disorder.
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., published in Molecular Psychiatry.
Abstract
Genome-wide association studies of lifetime and frequency of cannabis use in 131,895 individuals
Cannabis is among the most widely used psychoactive substances globally. The authors performed genome-wide association studies (GWAS) of lifetime cannabis use (N = 131,895) and of frequency of use (N = 73,374). For lifetime use, loci near CADM2 (rs35827242, p = 4.63E‑12) and GRM3 (rs12673181, p = 6.90E‑09) reached genome‑wide significance. For frequency of use, a locus near CADM2 (rs4856591, p = 8.10E‑09) was identified and is in strong linkage disequilibrium with the lifetime‑use signal.
Both lifetime use and frequency of use showed heritability and were genetically correlated with prior GWAS findings for cannabis use and cannabis use disorder, as well as with other substance use and cognitive traits. Polygenic scores derived from these GWAS predicted cannabis phenotypes in All of Us participants. A phenome‑wide association using a polygenic score for lifetime cannabis use replicated known links to substance use and mood disorders and revealed novel associations with autoimmune and infectious conditions. This work highlights the value of studying pre-addiction phenotypes in genomic discovery for cannabis use.