Overview
- The genome-wide association study published June 11, 2026 used nearly 900 genetically diverse Heterogeneous Stock rats to map DNA tied to cocaine self-administration, escalation and compulsive drug-seeking.
- Researchers found six significant genetic regions, including a chromosome 19 locus that contains Ces1 carboxylesterase genes, which showed the strongest link to how often and how compulsively rats took cocaine.
- Carboxylesterase enzymes made by Ces1 genes break down cocaine in the liver, so the findings suggest peripheral drug metabolism — not only the brain — can influence addiction vulnerability.
- Measured trait heritability ranged about 7%–16%, and the study replicated a human-associated locus (Trak2), giving the results a translational bridge while underscoring the traits’ polygenic nature.
- The team will run functional tests to see how Ces1 variants change enzyme activity and will mine their Preclinical Addiction Biobanks for blood and tissue biomarkers, but human validation and therapy development remain future steps.