One hit of cocaine may be all it takes to rewire DNA and leave a lasting mark on the brain, causing changes that persist for weeks, a new study suggests.
An estimated 42 million Americans have used cocaine at least once. Overall, cocaine use has declined across most age groups, with one exception: use among adolescents aged 12 to 17 tripled from 2021 to 2024, according to federal data.
‘We know that cocaine hijacks the reward machinery of the brain. Most people do not become addicted after using cocaine once, but many do after a second use or repeated exposures,’ Dr Ana Pombo, lead researcher, said.
‘However, we don’t know enough about what is happening to brain cells exposed to cocaine and whether these effects are long-lasting.’
To find out, Pombo and her colleagues turned to mice. Using a technique called genome architecture mapping, they observed how genetic material is organized within individual brain cells – a structure that reveals which genes are active.
The team focused on the brain’s reward hub, where dopamine is active. Within 24 hours, the genome’s structure had changed dramatically, and those changes did not fade. They persisted, and in some cases grew more pronounced, two weeks later.
‘The fact that we found such big changes that persist for two weeks is unexpected,’ Pombo said. ‘It suggests that the drug is leaving a longer-term “scar” in the genome of the brain cells.’
Pombo added that the lingering alterations may make the brain more responsive to future cocaine exposure, which could explain how even limited use paves the way for addiction.
Many cocaine users mistakenly believe that using the drug once or occasionally protects them from harm and addiction, but new research shows that a single dose rewires parts of the brain (stock image)
‘We still need to investigate how long these changes last for. Are they permanent, or can the brain cells recover over time? We also need to investigate how these changes translate to the risk of addiction,’ she said.
Inside every cell in the body is DNA – the long, stringy molecule that contains all of the genes, but DNA does not float around loose; It is folded up, twisted and packed into the cell’s nucleus.
How the DNA is folded matters. If a gene is on the outside of the fold, it’s easy for the cell to ‘read’ the coding instructions it contains.
If it’s buried deep inside, the cell can’t read it, and the gene remains turned off.
Pombo and her colleagues used a technique that lets them see exactly how DNA is folded inside brain cells.
They could tell which genes were on the outside, and thus were active, and which were buried, meaning inactive.
Then they compared brain cells from mice that had taken cocaine to brain cells from mice that had not.
Cocaine rearranged the folds. Some genes that were normally buried suddenly became accessible and turned on. Other genes that were normally accessible became buried and turned off. And these rearrangements lasted for weeks.
Specifically, one dose of the drug prompted the formation of around 1,700 new ‘chromatin domain insulation areas’ – barriers that block access to certain genes – while causing the loss of roughly 1,100 others, essentially removing roadblocks that were keeping other genes in check.
Researchers did not specify what a ‘dose’ of cocaine was defined as.
An estimated 42 million Americans have used cocaine at least once
Teen cocaine use is on the rise. Among adolescents aged 12 to 17, past-year use tripled from 0.1 percent in 2021 to 0.3 percent in 2024. Though the total number of users remains relatively small — 72,000 — the rise signals a shift in a demographic where use had been historically low
Some genes became more active, pumping out higher levels of neuropeptides, or signaling molecules that have been linked to addiction in humans. Meanwhile, other genes essential for normal brain cell function became less active.
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Previous research has shown that cocaine can turn genes on or off.
These latest findings, presented at the Federation of European Neuroscience Societies (FENS) Forum 2026, show that cocaine physically reorganizes the genome itself, moving entire regions of DNA from accessible to buried positions and vice versa.
When experts say cocaine hijacks the reward machinery in the brain, they mean the drug exploits the very system that evolved to keep humans alive.
This system rewards survival behaviors including eating, bonding and sex by releasing dopamine, a chemical that signals pleasure and encourages repetition.
Normally, after dopamine is released, it gets reabsorbed like a sponge mopping up a spill.
Cocaine blocks this reuptake, allowing dopamine to build up to unusually high levels and creating an intense, exaggerated feeling of pleasure.
The brain, wired to seek out dopamine triggers, starts treating the drug as something essential, like food or water.
But repeated use blunts the system. The brain reduces its dopamine receptors and produces less natural dopamine, making everyday pleasures feel dull.
Users need more of the drug just to feel normal.
Pombo’s findings add a new layer: cocaine physically rewires the DNA of the very cells that produce dopamine, leaving them hypersensitive to future doses.
