Genetic Mapping Identifies Potential New Targets for Cocaine Addiction
story<br>School of Medicine<br>Health Sciences
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Genetic Mapping Identifies Potential New Targets for Cocaine Addiction
Largest study of its kind uncovers how drug metabolism may drive addiction-like behavior
Cocaine use disorder is known to have a strong genetic component, but scientists have struggled to identify the specific genes involved, making it more difficult to develop targeted treatments. UC San Diego researchers have discovered that genes related to drug metabolism may hold the key. Photo credit: iStock/pashapixel
Story by:
Miles Martin
milesmartin@ucsd.edu
Published Date
June 11, 2026
Story by:
Miles Martin
milesmartin@ucsd.edu
Topics covered:
Cocaine use disorder
Addiction
Genetics
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Key Takeaways
Cocaine use disorder is known to have a strong genetic component, but scientists have struggled to identify the specific genes<br>UC San Diego researchers identified key genes, such as Ces1, that influence how cocaine is metabolized and how addiction develops<br>Results could help scientists develop better diagnostic tests and more effective treatments for substance use disorders
Researchers at the University of California San Diego have completed a massive genetic study that identifies key biological drivers of cocaine addiction, uncovering a potential new target for treatment that resides in the liver rather than the brain. The study, published in Nature Communications, used a genetically diverse group of nearly 900 rats to map the genetic markers associated with compulsive drug use.
Co-corresponding author Olivier George is a professor of psychiatry at UC San Diego School of Medicine.
"Finding a liver-based enzyme that shapes cocaine-taking behavior was a real ‘aha’ moment for us,” said co-corresponding author Olivier George, PhD, a professor of psychiatry at UC San Diego School of Medicine, whose lab led the addiction behavioral studies that provided the foundation for the research. “It reminds us that addiction isn’t only in the brain. It’s a complex puzzle involving how the entire body processes the drug.”
While it is well-known that cocaine use disorder has a strong genetic component, scientists have struggled to pinpoint the specific genes that make certain individuals more vulnerable to addiction.
Co-corresponding author Abraham Palmer is a professor of psychiatry at UC San Diego School of Medicine.
“Identifying those genes in an important goal, because drugs could then be developed to target those genes, shifting genetically susceptible people to become more like genetically resistant people,” said co-corresponding author Abraham A. Palmer, PhD, professor of psychiatry at UC San Diego School of Medicine, who led the project's intensive genetic modeling and analysis.
Current research in this area often focuses on the brain, but the UC San Diego team’s findings suggest that how the body breaks down — or metabolizes — cocaine may be just as critical in determining whether somebody develops an addiction.
The researchers identified a specific group of genes, known as Ces1, which are responsible for creating the enzyme that metabolizes cocaine. The study found that variations in these genes are closely linked to how frequently and compulsively rats self-administered the drug. By utilizing heterogeneous stock rats — a model system capable of mimicking the vast genetic diversity found in human populations — the team was able to capture the critical differences between individuals who are genetically susceptible to addiction and those who are naturally more resistant.
Analyzing millions of genetic markers in each animal, the team was able to identify six major genetic regions linked to addiction-like behaviors, such as the escalation of drug intake and the time elapsed between doses. Their findings suggest that by targeting the enzymes that metabolize cocaine with medicines, scientists might be able to alter how the drug affects the body, potentially reducing its addictive impact.
“This work showcases the power of long-term, team-science collaboration that pairs experts in rodent behavior with quantitative geneticists,” said Palmer. “A decade of coordinated effort across multiple cohorts and federal partners made possible a discovery that no single lab could achieve alone.”
The findings also replicated a known genetic link found in humans (Trak2), providing a vital translational bridge between animal research and human medicine. This replication strengthens the argument that the biological pathways identified in the lab could eventually lead to real-world therapies.
This image shows the Ces1 protein, which plays a role in metabolizing cocaine.
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