*The article was written by Fabricio Pamplona, PhD in Pharmacology, from the Federal University of Santa Catarina (UFSC), and published on The Conversation Brasil platform.
The debate on the Cannabis is generally trapped in a simplistic dichotomy, between those who see it as a dangerous substance and those who see it as a medicinal plant or an expression of freedom. The perception and stigma surrounding the use of this plant comes from the direct association between its consumption and “getting addicted”, in popular parlance. But a study recently published by the prestigious journal Neuropsychopharmacology offers a more in-depth look, literally going down to users’ DNA.
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The study “The genetics of Cannabis lifetime use” led by Yale researchers who studied the genetics of Cannabis across the lifespan (CanLU) — that is, the biological factors that increase the likelihood that a person will suffer Cannabis – regardless of the development of an addiction. The team analyzed genetic data from more than 250,000 people of different ancestry, in one of the largest studies of its kind ever carried out.
The results are fascinating: they suggest that experimenting Cannabis it may be more linked to the genetics of curiosity and the search for new experiences than to a direct predisposition to addiction.
The main finding of the study was the strong association between lifetime use of Cannabis with a gene called CADM2 (Cell Adhesion Molecule 2). The most significant genetic variant (SNP) found in the study was CADM2*rs7609594, a finding that validates previous studies.
CADM2 is a gene already known to be involved in exploratory behaviors and positive impulsivity. This same genetic region had previously appeared in research on openness to experience, greater number of sexual partners and the propensity to take moderate risks. In other words, the same neural circuits that help us explore new things and seek pleasure can also influence the decision to experiment. Cannabis. That makes sense, right?
CADM2 has been called by neuroscientists the “curiosity gene” – not in a romantic sense, but in a functional sense. It codes for a protein involved in adhesion between neurons, essential for the efficiency of brain connections. Changes in this gene are associated with greater sensitivity to reward and a greater willingness to try something new.
Interestingly, the same genetic mechanisms that lead someone to try new foods, ideas, or cultural practices also appear to modulate the likelihood of trying psychoactive substances. So this is not a “marijuana gene,” but an exploration gene – an evolutionary trait that could have been advantageous for human survival, by favoring individuals willing to explore unfamiliar environments. The innate curiosity of individuals also makes them want to explore “new states of consciousness”.
Experiencing is not the same as being addicted
A crucial point of research has been the comparison between the genetics of lifetime use (CanLU) and the genetics of cannabis use disorders (CanUD), that is, research into the relationship between “those who only experiment” and “those who develop a dependence” on the use of the plant.
Although there is a moderate genetic correlation (rg = 0.58) between the two behaviors, the study led by Professor Uri Bright of the Yale School of Medicine and colleagues demonstrated that the loci (locations in the genome) involved in occasional drinking are significantly different from those leading to compulsion. This reinforces the idea that “curiosity” and “compulsion” follow different biological paths.
While addiction (CanUD) is strongly correlated with psychiatric disorders, sleep disorders, and cardiovascular disease, CanLU showed positive associations with exploratory personality traits and even higher educational attainment. These data are particularly interesting: although smoking is negatively correlated with education, cannabis use appears, in part, to be more prevalent among more educated people, perhaps reflecting cultural changes and less stigmatizing social perceptions.
The study also distinguished CanLU from lifetime tobacco use, confirming that despite high behavioral overlap, there are clear genetic differences, indicating that CanLU is not genetically identical to the “smoking” phenotype.
And what does this mean for medicine and society?
Bright and colleagues’ findings have direct implications for the future of cannabinoid medicine and pharmacogenetics.
First, because they show that the response to cannabis consumption is influenced by individual genetic factors, both at the behavioral and pharmacological level. Genes such as CADM2, CYP2C19, and FAAH can modulate how the body metabolizes and responds to CBD and THC, which explains why some patients experience excellent treatment results, while others see no benefit.
Second, because the distinction between “use” and “abuse” has a biological basis – and this can help reduce the stigma surrounding Cannabisparticularly in therapeutic contexts. To use Cannabis does not automatically imply a genetic predisposition to addiction. Getting into a state of addiction is another story.
These results also provide insights for public policies: if the genetics of occasional use are different from those of abuse, prevention and regulation strategies must be further refined, distinguishing curiosity and vulnerability, or between occasional user and dependent.
The use of Cannabis throughout life is not only a matter of social or moral choice, it is also an expression of the biology of human curiosity. Understanding this genetic basis does not serve to justify its use, but to see it with nuance, science and empathy and, who knows, to chart the path towards a health policy freer from prejudice.
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