UC San Diego Scientists Identify Genes Linked to Cocaine Addiction and a Surprising Target Outside the Brain

Researchers found:

• Six genetic regions linked to cocaine addiction behaviors.
• Strong evidence connecting the Ces1 gene family to cocaine use risk.
• A liver enzyme may influence addiction vulnerability.
• Addiction risk may depend on both brain function and drug metabolism.
• Future treatments could potentially target the body’s processing of cocaine rather than only the brain.

A team of researchers at the University of California San Diego has identified genetic factors linked to cocaine addiction and uncovered an unexpected player in the process: the liver.

The study, published in the journal Nature Communications, found that a liver enzyme involved in breaking down cocaine may influence whether someone develops compulsive drug use. The findings challenge the long-held assumption that addiction is driven primarily by changes in the brain and suggest future treatments could target the body as well.

The research comes as the United States continues to face a deadly overdose crisis fueled by fentanyl and other synthetic drugs. According to the U.S. National Institute on Drug Abuse (NIDA), cocaine use remains a major public health concern because it can lead to addiction, overdose, heart problems, stroke, and death.

For California, where public health officials continue investing in addiction prevention and treatment programs, the findings may eventually contribute to new approaches for helping people struggling with substance use disorders.

Why This Research Matters

Scientists have known for years that genetics play a significant role in addiction risk. However, identifying the specific genes involved has proven difficult.

Researchers at the UC San Diego School of Medicine analyzed nearly 900 genetically diverse rats to better understand why some individuals develop compulsive cocaine use while others do not.

The team identified six major genetic regions associated with addiction-like behaviors, including escalating drug use and increased motivation to seek cocaine.

Their most significant finding involved a group of genes known as Ces1, which produce enzymes that help metabolize cocaine in the liver.

Researchers found that differences in these genes were strongly associated with how frequently and compulsively the rats consumed the drug.

A Potential Treatment Target Outside the Brain

One of the study’s most surprising conclusions is that addiction may not be solely determined by brain chemistry.

Olivier George, professor of psychiatry at the UC San Diego School of Medicine and one of the study’s corresponding authors, said the discovery changed how researchers think about addiction biology.

“Finding a liver-based enzyme that shapes cocaine-taking behavior was a real lightbulb moment for us,” George said in a university statement.

He added that addiction is “a complex puzzle involving how the entire body processes the drug.”

The finding raises the possibility that future medications could alter how cocaine is metabolized, reducing its addictive effects before it reaches the brain’s reward pathways.

That approach could represent a major shift in addiction treatment research, which has historically focused on brain receptors and neurotransmitters.

What Is Ces1 and Why Is It Important?

The Ces1 gene family produces enzymes that help break down various substances, including cocaine.

The study found that genetic variations affecting these enzymes may influence how long cocaine remains active in the body and how strongly users experience its effects.

Researchers believe that changing how these enzymes function could potentially reduce the rewarding effects of cocaine and lower the risk of addiction.

While the findings are promising, scientists caution that the research remains in an early stage and was conducted in animals rather than humans.

Connection to Human Addiction Research

The study also confirmed the role of Trak2, a gene previously linked to addiction risk in human studies.

Researchers say this strengthens confidence that the biological pathways identified in the laboratory may also be relevant to people.

Montana Kay Lara, the study’s lead author and a postdoctoral researcher at UC San Diego, said the findings validate a theory scientists have debated for decades.

“It gives us a concrete target to test whether changing the way cocaine is metabolized can reduce the drive toward compulsive use,” Lara said.

The Real-World Risks of Cocaine Use

According to NIDA, cocaine use can cause serious health complications even after short-term exposure.

Potential effects include:

• High blood pressure
• Elevated heart rate
• Increased body temperature
• Anxiety and paranoia
• Tremors and muscle spasms

Long-term use can increase the risk of:

• Heart attack
• Stroke
• Seizures
• Brain hemorrhage
• Cognitive impairment
• Memory and decision-making problems

Federal health officials also warn that cocaine is increasingly contaminated with fentanyl, significantly increasing overdose risk.

Researchers are now studying how these genetic mutations alter enzyme function and whether the findings can eventually lead to medications that reduce cocaine addiction risk.

The team is also analyzing extensive biological samples collected during the project, including blood, urine, brain tissue, and other materials. Those samples may help identify biomarkers capable of predicting an individual’s risk for substance use disorders.

While any treatment based on these findings remains years away, the study offers a new direction in addiction science and highlights how genetics, metabolism, and behavior work together to shape addiction risk.

For California families affected by substance use disorders, the research provides something often missing from addiction coverage: evidence that biology may play a larger role than previously understood and that new treatment strategies may eventually emerge from that understanding.