Understanding why some people become addicted to cannabis and others don't is one of the great questions in public health. The most recent evidence makes it clear that Genetics plays a significant role in the onset, frequency, and risk of cannabis use disorderBut it does not act alone: ​​it is intertwined with the environment, the age of onset, the power of the product, and psychosocial factors.
Although most people who try it will not develop a problem, various sources estimate that almost a 30% could develop a cannabis use disorderWith global usage around 200 million people and a context of decriminalization and legalization in several countries, researchers have put human DNA under the microscope to map genomic regions, specific genes, and correlated traits with lifetime consumption and frequency of use.
What genetic science is investigating about cannabis
A genome-wide association study (GWAS) using data from 131.895 participants from 23andMe explored whether variations in DNA are related to ever having tried cannabis and the frequency of use. This strategy compares hundreds of thousands of genetic variants spread across the genome and detects statistically robust signals where there are more genetic changes in those who share a specific traitIn this case, cannabis use.
The team, based at the University of California, San Diego (UC San Diego), set out to identify not only specific associations, but also biological systems that connect consumption with brain function and behaviorThe idea is that, if the molecular pathways involved are discovered, it could open doors to prevention strategies and even future therapeutic targets.
The study, published in the journal Molecular Psychiatry, underscores a complex reality: the genetics of cannabis use overlaps with the genetics of multiple psychiatric, cognitive, and physical health traitsIn other words, they are not separate universes; they share part of the biological substrate.
The genes under the microscope: CADM2 and GRM3
Among the most consistent findings are two genes. One is CADM2, a molecule involved in the assembly and signaling between neurons, especially in the brain. It had already been linked to impulsivity, obesity and metastasis In other contexts, it is now associated both with the likelihood of having tried cannabis and with the frequency of use. This convergence suggests that certain personality traits and control circuits may be involved in decision-making and repeated use.
The second is GRM3, which encodes a metabotropic glutamate receptor linked to synaptic communication and long-term plasticity. It had previously been associated with schizophrenia and bipolar disorderTheir signal in cannabis consumption does not imply that smoking directly leads to these disorders; rather, it indicates that some biological pathways are common, so that a portion of the genetic risk is shared between cannabis use and certain psychiatric conditions.
More signals in the genome: dozens of loci and their frequency
In addition to CADM2 and GRM3, a secondary analysis identified 40 additional genes linked to lifetime cannabis use, and four genes associated with frequency of consumptionOf particular interest is that 29 of these genes had not previously been linked to cannabis-related traits, thus expanding the map of possible biological pathways involved.
To understand the scope, the researchers compared the genetic profiles with large, independent health repositories (e.g., the NIH's All of Us program and the Vanderbilt biobank). They found that a genetic predisposition to cannabis use correlates with more than 100 different featuresThis is not determinism, but rather statistical coincidences that point to shared biological pathways.
Among the most prominent genetic correlations are several thematic blocks:
- psychiatric disorders: schizophrenia, ADHD, anxiety and depression.
- Cognitive performance and behavior: executive function and risk-taking.
- Physical Health: diabetes, chronic pain and coronary artery disease.
- Health behaviors: higher probability of tobacco use.
- Infectious diseases: association with HIV and viral hepatitis.
- Autoimmune diseases.
The existence of these correlations does not imply direct causation. Simply put, it indicates that some pieces of the genetic puzzle that predispose individuals to substance use also play a role in other factors. other medical or behavioral conditionsThis may be due to shared pathways, pleiotropy, or interaction with environmental factors.
Non-genetic factors that increase the risk of addiction
The role of genetics is undeniable, but it doesn't explain everything. There are modifiable factors that strongly impact the likelihood of developing a cannabis use disorder, so prevention remains key. We are not condemned by our genome.
Frequency of consumption
The strongest predictor is how often it is consumed. In population terms, The higher the frequency, the greater the likelihood of a disorder.It is a dose-response relationship that clinical practice consistently observes.
Duration of consumption
Time also matters. Accumulating years of use increases the risk. The longer the consumption over a lifetime, greater the probability of problems.
Cannabis potency
As potency (measured by THC concentration) increases, the risk of disorder may also increase. Observational studies have found associations between high THC levels and a greater likelihood of addictionespecially when combined with frequent use.
Psychosocial factors
Personal and social context modulates vulnerability. Risk factors have been described as follows: depressed mood, anxiety, persistent behavioral problems in childhood or adolescence and the presence of a pre-existing psychiatric disorder. Other contributing factors include the use of other substances (alcohol, tobacco, or others), fewer years of education, parental cannabis use, and adverse childhood experiences (physical, emotional or sexual abuse) and stressful life events, such as unemployment or financial difficulties.
Genetics and schizophrenia: a bidirectional link with consumption
Another study, conducted by teams from King's College London and the Queensland Institute of Medical Research, addressed the relationship between cannabis use and the genetic risk of schizophrenia. With 2.082 healthy participants (1.011 users), they calculated a polygenic risk profile for schizophrenia and examined consumption patterns. The results indicated that Those who accumulated more variants associated with schizophrenia were more likely to use cannabis and to do so in larger quantities..
This observation suggests a two-way link: on the one hand, cannabis use has been associated with an increased risk of psychosis; on the other, part of the relationship could be explained by the fact that Certain genetic variants predispose individuals to both schizophrenia and substance abuse.It is a reminder of the complexity of the interplay between genes and environment, and that there is no single cause that explains everything.
Epigenetics and cannabis: traces in DNA
Epigenetics studies heritable changes in gene expression that do not alter the DNA sequence. One of its best-known mechanisms is the DNA methylationwhich acts like a switch that turns genes on or off depending on the tissue and environmental context. Several studies indicate that cannabis use leaves measurable epigenetic traces.
In a small study with non-human primates, pregnant macaques received a THC-containing edible daily during gestation. Their offspring showed 581 differences in methylation compared to controls, with one striking finding: 98% of the changes were concentrated in the placentaFurthermore, many of these changes overlapped with patterns found in human placentas of infants who were later diagnosed with autism spectrum disorder.
THC crosses the placenta and binds to cannabinoid receptors in fetal tissue. Since some women use cannabis during pregnancy (for example, to try to relieve nausea), the authors emphasize the importance of providing accurate information about the risks. The placenta produces neurotransmitters that can influence the developing brain; therefore, these alterations could have long term consequencesThe practical recommendation was to open a more systematic clinical dialogue on cannabis use before and during pregnancy.
Beyond prenatal exposure, epigenetic changes have been studied in adults. A cohort of 3.600 people in the United States were evaluated for consumption habits and blood methylation profiles. In the questionnaire, 85% reported never having used drugs, 6% used them on special occasions, 1,4% once a week, 2,1% between 3 and 5 times a week, and 2% daily. Blood samples revealed... small methylation changes in genes related to neuromuscular balancewhich grew in magnitude as the frequency of consumption increased, a dose-response pattern.
The authors were cautious: ideally, brain tissue, the primary target of cannabis, would be analyzed, but such samples are difficult to obtain. Even so, the presence of traces in blood suggests that Consumption can leave lasting biological marksThe parallel with tobacco, whose epigenetic effects are well characterized and even detected in children of smoking mothers, reinforces the plausibility of these findings.
Population overview and lack of specific drugs
In Europe, the latest regional report indicates that 15,4% of young people aged 15 to 34 used cannabis in the past year. By country, Italy leads with 21,5%, followed by Croatia (20,3%) and Spain (19,4%)The lowest figures are observed in Portugal (4,9%), Greece (4,5%), and Hungary (3,4%). Overall, 8,4% of European adults (15–64 years old) reported consumption in the past year, and around 1,5% consume it daily or almost daily.
In the United States, where it is already legal in 24 states, documents from federal agencies estimated that Millions of people meet the criteria for cannabis use disorderA recent report mentions 20,6 million cases in 2024. This scenario contrasts with the absence of FDA-approved drug therapies to treat the disorder, leaving the focus on prevention, psychosocial interventions, and clinical support.
The usefulness of GWAS and epigenetic studies is twofold: they help to identify people with greater vulnerability and prioritize biological targets which, later on, could guide the development of drugs or personalized prevention strategies.
What do these findings imply for prevention and treatment?
First, the risk is multifactorial: knowing one's genetic profile adds information, but it doesn't seal one's fate. In fact, reduce frequency and durationAvoiding high-potency products and addressing underlying anxiety or depression can, in practice, decrease the chances of developing a substance use disorder.
Second, pediatrics and obstetrics must explicitly address cannabis use. Data in primates and knowledge about the vulnerability of the developing brain They justify preventive conversations in the consultation, especially in the case of planned or ongoing pregnancies.
Third, the genetic overlap with smoking, psychiatric disorders, and infectious diseases calls for comprehensive approaches. Programs that combine mental health screening, addressing polydrug use and education about biological risks can be more effective than isolated strategies.
Fourth, future research should refine the clinical translation: improving individual prediction, defining high-risk profiles that benefit from early interventions, and studying whether modular routes such as those associated with CADM2 or GRM3 It has a significant impact on consumer behavior and its consequences.
The picture that science paints is not monochromatic: there are genes that predispose, traits and environments that exert influence, and decisions that make all the difference. By integrating genomic, epigenetic, and epidemiological evidence, a practical message emerges: inform, prevent and personalizeThe better we understand these pieces, the closer we will be to reducing harm, guiding those at greatest risk, and eventually opening the door to specific treatments for cannabis use disorder.
