A polygenic risk score for adult cannabis use disorder predicted substance use, impulsivity traits, and white matter brain differences in teenagers as young as 14.
Parents and educators; genetics and addiction researchers
Genetic risk for adult CUD is visible in brain and behavior by age 14
What the researchers found
Higher genetic risk for CUD was associated with greater cannabis exposure, more novelty/sensation seeking, higher impulsivity, and lower white matter integrity from age 14. Mediation models showed novelty seeking and impulsivity partially explained the path from genetic risk to cannabis use.
Why it matters
This is one of the first studies to show that adult CUD genetic risk is already visible in adolescent brain structure and behavior.
The numbers in context
CUD-PRS and cannabis exposure: beta = 0.098, P < 0.001. CUD-PRS and novelty seeking: beta = 0.105, P < 0.001. CUD-PRS and impulsivity: beta = 0.106, P < 0.001.
How the study worked
Longitudinal data from the IMAGEN cohort with assessments at ages 14 (n=1,762), 19 (n=1,175), and 23 (n=1,139). Polygenic risk scores related to behavioral measures, substance use, and brain imaging.
What this study cannot tell us
Effect sizes are small (betas around 0.1). European-ancestry cohort only.
How to read the evidence
Large longitudinal cohort with neuroimaging and genetic data; moderate because of small effect sizes.
When this study was published
2025 study with data spanning ages 14 to 23
The bigger picture
Genetic risk for addiction works partly through personality traits and brain structure, suggesting these could be intervention targets.
Questions still open
- Could impulsivity-targeted interventions in genetically at-risk adolescents prevent CUD?
Common questions
Does a high polygenic risk score mean someone will develop cannabis use disorder?
What is fractional anisotropy?
Read the original research
Impulsivity behaviors and white matter mediate the relationship between genetic risk for cannabis use disorder and early cannabis use in adolescents.
Addiction (Abingdon, England), 120(5), 984-996
Citation
Cupertino, Renata Basso; Medland, Sarah Elizabeth; Ottino-Gonzalez, Jonatan; Cao, Zhipeng; Juliano, Anthony; Pancholi, Devarshi; Banaschewski, Tobias; Bokde, Arun L W; Desrivières, Sylvane; Flor, Herta; Grigis, Antoine; Gowland, Penny; Heinz, Andreas; Brühl, Rüdiger; Martinot, Jean-Luc; Martinot, Marie-Laure Paillère; Artiges, Eric; Nees, Frauke; Orfanos, Dimitri Papadopoulos; Lemaitre, Herve; Paus, Tomáš; Poustka, Luise; Hohmann, Sarah; Fröhner, Juliane H; Smolka, Michael N; Walter, Henrik; Whelan, Robert; Schumann, Gunter; Conrod, Patricia; Callas, Peter; Garavan, Hugh; Mackey, Scott. (2025). Impulsivity behaviors and white matter mediate the relationship between genetic risk for cannabis use disorder and early cannabis use in adolescents.. Addiction (Abingdon, England), 120(5), 984-996. https://doi.org/10.1111/add.16750
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