Genetics are not the sole determiner of one's destiny
Why is it some people only use cannabis once, while others become frequent users and some go on to develop cannabis use disorder? The first study of its kind to look at the trait of frequency of cannabis use has shed light on the possible genetic factors at play.
Schulich School of Medicine & Dentistry postdoctoral researcher Hayley Thorpe collaborated with University of California San Diego School of Medicine researchers to conduct the study while serving as a visiting scholar there. The study published in Molecular Psychiatry (https://www.nature.com/articles/s41380-025-03219-2) analyzed data from more than 130,000 individuals.
Thorpe and her collaborators found cannabis use is not associated with a single gene but a combination that could contribute to whether someone is likely to use frequently.
"Our study is specifically focused on the genetics of cannabis use and what relationships these genetics have with health," said Thorpe. "How someone engages with cannabis and the habits surrounding its use are very important to health outcomes."
There is an urgent need for clinical treatments to address cannabis use disorder and the harms of heavy use, Thorpe said. Despite the disorder affecting up to 27 per cent of people who have tried cannabis, there are no pharmacological treatment options currently available. Thorpe hopes uncovering the genetic pathways linked to use will open the door to new interventions.
The genes at play
The study used a method called genome-wide association study (GWAS) which scans the entire genome to find common genetic variants associated with traits of interest. Researchers investigated two traits of interest, cannabis use in one's lifetime and the frequency.
Thorpe's team identified genetic variation in two genes of interest: CADM2 and GRM3.
Past studies have linked CADM2 to impulsivity, risk-taking behaviour and likelihood of using cannabis, but Thorpe said this is the first time it has been tied to frequency of cannabis use.
GRM3, meanwhile, had never before been implicated in cannabis use.
The lifetime cannabis use trait includes people who use cannabis infrequently, perhaps even once. These individuals do not represent the genetics of regular cannabis use, whereas the frequency of use trait includes individuals who may experience the effects of reoccurring use.
By separating these stages, researchers were able to explore the genetics of pre-addiction behaviours.
"Our study is the first to use GWAS to examine any of the intermediary stages of cannabis use through frequency of use," said Thorpe. "Examining this trait can shed light on the biology and health associations of regular, but non-pathological cannabis use."
However, Thorpe cautions against thinking of DNA as destiny.
"First and foremost, we hope everyone understands that genetics are not the sole determinant of one's destiny. How someone engages with cannabis use and the habits surrounding its use are very important to its health outcomes," said Thorpe.
Improving lives and stigma
While Thorpe acknowledges that genetics are not the only factor at play, she does emphasize that they contribute significantly to an individual's substance use vulnerability.
The potential benefits of understanding these factors are two-fold as that knowledge could both help develop treatments for cannabis use disorder and reduce stigma.
"When we understand the genetics of cannabis use, we can delve deeper into the biological mechanisms underpinning the effects of its use, which can lead to new therapeutic interventions," said Thorpe.
Genetics also play a role in how an individual may experience the effect of a drug, an important factor in the likelihood of developing a substance use disorder.
"We don't want anyone's takeaway to be that cannabis use inevitably leads to worse health," said Thorpe. "Our study's focus was the associations between the genetics of cannabis use and health, not cannabis use itself."
Experiences with a recreational substance like cannabis can vary from person to person, further increasing the need to understand the mechanisms at play that are not within an individual's control, Thorpe said.
Her team hopes to explore additional cannabis-related traits such as heaviness of use, withdrawal and cravings.
For Thorpe, the importance of the work is about more than decoding DNA but rather creating an understanding of cannabis use to reduce stigma, inform public health and create treatments that improve lives.
