In a groundbreaking collaboration, researchers at the University of California San Diego School of Medicine partnered with the genetic testing company 23andMe to delve deep into the genetic foundations underpinning cannabis use. Their investigation, recently published in the prestigious journal Molecular Psychiatry, elaborates on the complex relationships between genome variants and cannabis consumption habits, revealing intricate connections with psychiatric disorders, cognitive function, and physical health outcomes. This pioneering study offers promising avenues for the future development of targeted prevention and treatment strategies for cannabis use disorder, an increasingly relevant public health concern.
Cannabis, albeit widely used around the globe, remains poorly understood in terms of its long-term impacts on human health. Dr. Sandra Sanchez-Roige, associate professor of psychiatry at UC San Diego and the senior author of the study, emphasizes that despite its prevalence, much remains unknown about why some individuals transition from experimentation to problematic use, while others do not. A key objective of the team was to elucidate the genetic factors influencing early-stage behaviors that could indicate vulnerability to cannabis use disorder, a condition characterized by significant interference with daily functioning.
Epidemiological data indicate that approximately 30% of individuals who try cannabis eventually develop cannabis use disorder. This percentage is striking, given that most users do not progress to addiction. Dr. Sanchez-Roige highlights the urgency of identifying biological markers that distinguish those at higher risk. Understanding the genetic architecture of these intermediate behavioral traits stands to revolutionize interventions aimed at halting progression to disorder, potentially mitigating the rising health burden linked to cannabis misuse.
Utilizing a genome-wide association study (GWAS)—a powerful analytical tool to correlate genetic variants across the genome with specific traits—the team analyzed genetic and behavioral data from 131,895 volunteers who are part of 23andMe’s research cohort. Participants self-reported on their lifetime cannabis use and frequency of consumption, providing a robust dataset for interrogating the heritable elements associated with cannabis-related behaviors. GWAS technology permitted an unbiased scan for DNA regions linked with cannabis use, facilitating the discovery of novel genetic loci implicated in this complex trait.
Two genes emerged as primary loci that harbor significant associations with cannabis use. The first, Cell Adhesion Molecule 2 (CADM2), is renowned for its involvement in neuronal connectivity and signaling. This gene has been previously implicated in behavioral traits related to impulsivity and risk-taking, which align with predispositions towards substance use. The study confirmed CADM2’s association not only with whether an individual ever used cannabis but also with the intensity and frequency of use, underscoring its multifaceted role in the behavioral spectrum leading to cannabis engagement.
The second prioritized gene identified was Metabotropic Glutamate Receptor 3 (GRM3). This gene plays a vital role in synaptic communication and neuroplasticity—the brain’s ability to adapt structurally and functionally over time. GRM3’s linkage to psychiatric conditions such as schizophrenia and bipolar disorder has been established, suggesting shared neurobiological pathways across diverse neuropsychiatric phenotypes. Its association with cannabis use frequency offers intriguing insights into the potential neural mechanisms through which cannabis may influence or be influenced by underlying psychiatric vulnerabilities.
Beyond these two prominent genes, secondary analyses uncovered an additional 40 genes associated with lifetime cannabis use and four genes related to usage frequency. Remarkably, 29 of these genes had not been previously connected with cannabis-related behaviors, opening new frontiers for biological research and clinical exploration. This expanded genetic landscape highlights the polygenic and multidimensional nature of cannabis use, which intersects with a multitude of brain functions and systemic physiological processes.
Importantly, the researchers extended their genetic correlations by investigating links with thousands of traits cataloged in two expansive datasets: the National Institutes of Health’s All of Us Research Program and the Vanderbilt University Medical Center biobank. These comprehensive repositories allowed the team to chart the broad health consequences of genetic predispositions to cannabis use, unveiling associations with over 100 traits. These traits encompassed psychiatric disorders such as ADHD, anxiety, depression, and schizophrenia; cognitive attributes including executive function and risk-taking behavior; as well as physical health issues like diabetes, chronic pain, and coronary artery disease.
Further illuminating the complex interplay between cannabis use and other behaviors, genetic predisposition for cannabis consumption was also connected with increased tendencies toward tobacco use and susceptibility to infectious diseases including HIV and viral hepatitis. Moreover, autoimmune diseases emerged as part of the correlated health spectrum, revealing unexpected intersections between genetics of cannabis use and immune system regulation. These findings affirm cannabis use as a multifaceted phenotype with broad systemic implications beyond neural circuits alone.
This study stands among the pioneering genome-wide association efforts focusing on behaviors antecedent to cannabis use disorder. As Dr. Hayley Thorpe, a postdoctoral researcher and the study’s first author, explains, dissecting intermediate traits enables researchers to sketch a more granular map of the genetic risk trajectory, illuminating how predispositions unfold prior to the development of clinical addiction. This approach may ultimately furnish early biomarkers that predict and prevent the onset of cannabis-related disorders.
With no FDA-approved pharmacotherapies currently available to treat cannabis use disorder, the identification of the underpinning molecular systems marks a critical advance toward therapeutic discovery. The authors express hope that the genetic insights gleaned from this extensive GWAS will catalyze the design of future interventions—both pharmacological and behavioral—that target the biological pathways driving susceptibility. Such innovations could transform clinical practice by enabling precision medicine approaches tailored to individual genetic risk profiles.
The interdisciplinary nature of this research underscores the importance of collaboration between academic institutions and industry partners. Alongside UC San Diego’s team, contributors from 23andMe, Western University, Washington University in St. Louis, and Vanderbilt University Medical Center combined their expertise to produce a nuanced picture of cannabis genetics. This exemplifies how big-data approaches coupled with large-scale participant engagement can accelerate elucidation of complex behavioral traits.
Funding for the study was provided by prestigious sources including the National Institute on Drug Abuse at the NIH and the Tobacco-Related Disease Research Program. Ethical oversight was adhered to meticulously, with participant consent obtained through an AAHRPP-accredited protocol managed by the Salus Institutional Review Board, ensuring adherence to rigorous human research standards.
This landmark investigation fundamentally enriches our understanding of how genetic variation informs cannabis use and its broad impacts on mental and physical health. As cannabis legalization expands globally, these findings are particularly timely, equipping the medical and scientific communities with novel frameworks to confront the evolving landscape of cannabis consumption and its associated disorders.
Subject of Research: Genetic influences on cannabis use and associated health outcomes
Article Title: Genomic Insights into Cannabis Use Illuminating Psychiatric and Physical Health Links
News Publication Date: October 13, 2025
Web References:
- Molecular Psychiatry journal
- National Institutes of Health All of Us Research Program
- Vanderbilt University Medical Center biobank
References:
- Sanchez-Roige et al., Molecular Psychiatry, 2025
- NIH grants R01 DA050721, P50DA037844, P30DA060810
- Tobacco-Related Disease Research Program grant T32IR5226
Keywords: Cannabis, Addiction, Behavioral addiction, Behaviorism, Genetics
