Scientists have identified two key genes that may influence people’s likelihood of using cannabis frequently, in what researchers say is the largest genetic study of cannabis use to date.
The research, published in the journal Molecular Psychiatry, analysed genetic data from 131,895 participants and found that variants in genes controlling brain signalling and impulsivity were more common among regular cannabis users.
The study also identified more than 40 additional genetic variants linked to risk-taking and schizophrenia as well as chronic illnesses such as diabetes and heart disease.
“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, lead author of the study.
Scientists from the University of California, San Diego School of Medicine and the DNA testing company 23andMe identified two primary genes of interestknown as CADM2 and GRM3.
American participants answered questions on a survey about their cannabis use, including whether they had used the drug before, and if so, how frequently.
Researchers then conducted a genome-wide association study (GWAS) to outline any patterns in the genetic data of frequent cannabis users.
“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, 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 analysis showed that the first gene, Cell Adhesion Molecule 2 (CADM2), plays a role in how brain cells communicate with each other. Previous research has connected this gene to impulsive behaviour, obesity, and certain cancers.
The second gene, Metabotropic Glutamate Receptor 3 (GRM3), is involved with brain communication and plasticity, and is associated with psychiatric disorders such as schizophrenia and bipolar disorder.
The researchers hope their findings could help identify people at higher risk of developing Cannabis Use Disorder (CUD).
“Cannabis is widely used, but its long-term effects on health remain poorly characterized. 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 validate their findings, the team compared their data to two additional large-scale data sets: the All of Us study and the Vanderbilt University Medical Center’s biobank.
This broader analysis linked lifetime and frequent cannabis use to more than 100 different conditions and traits. These included mental health conditions such as schizophrenia, ADHD, anxiety and depression, as well as cognitive abilities like decision-making and risk-taking behaviour. Physical health problems, including diabetes, chronic pain and heart disease, were also linked to the same genetic variants.
The researchers believe that by understanding the genetic makeup of lifetime and frequent cannabis users, they may be able to predetermine who may be at risk not only of CUD, but also of other traits and conditions associated with the genes cannabis users carry.
“Cannabis use exists on a continuum,” said first author Hayley Thorpe. “By studying these intermediate traits, we can begin to map how genetic risk unfolds before cannabis use disorder develops.”
While the study represents the largest genetic analysis of cannabis use to date and provides new insights into the biological mechanisms that may influence why some people are more likely to use cannabis frequently than others, the researchers emphasise that genetics is only one factor among many that influence drug use behaviour, with environmental and social factors also playing important roles.
