A single use of cocaine may be sufficient to alter brain cell DNA and induce lasting changes that persist for weeks, according to a new study. These alterations could potentially heighten an individual's susceptibility to addiction, even with limited exposure.
The study, presented at the Federation of European Neuroscience Societies (FENS) Forum 2026, utilized genome architecture mapping in mice to observe changes in brain cells within the brain's reward hub. Researchers found that within 24 hours of a single cocaine dose, the organization of genetic material within brain cells changed significantly. These structural modifications did not diminish and, in some cases, became more pronounced two weeks later.
"The fact that we found such big changes that persist for two weeks is unexpected," said Dr. Ana Pombo, the study's lead researcher. "It suggests that the drug is leaving a longer-term ‘scar’ in the genome of the brain cells."
These persistent alterations may make the brain more sensitive to future cocaine exposure, offering a potential explanation for how even infrequent use can lead to addiction. The researchers noted that while most individuals do not develop addiction after a single use, many do after a second or repeated exposures. The study aimed to understand the effects on brain cells and whether these effects are long-lasting.
Cocaine's impact on the brain's reward system involves hijacking the dopamine pathways. Normally, dopamine, a chemical signaling pleasure and encouraging repetition of rewarding behaviors, is reabsorbed after release. Cocaine blocks this reuptake, leading to an artificial buildup of dopamine and an intense feeling of pleasure. The brain can begin to prioritize the drug over essential needs like food or water.
Over time, repeated use can desensitize the brain's dopamine system, requiring more of the drug to achieve normal feelings and diminishing pleasure from everyday activities. Pombo's research adds that cocaine physically reorganizes the DNA within dopamine-producing cells, potentially making them hypersensitive to subsequent doses.
Previous research indicated that cocaine could activate or deactivate genes. This latest study demonstrates that cocaine physically reshapes the genome, moving entire DNA regions between accessible and inaccessible positions. Specifically, one dose was found to create approximately 1,700 new barriers to gene access (chromatin domain insulation areas) while removing about 1,100 existing ones.
Some genes became more active, increasing the production of neuropeptides linked to addiction in humans, while other genes crucial for normal brain cell function became less active.
While the study focused on mice, the findings raise concerns about human use. An estimated 42 million Americans have used cocaine at least once. Although overall cocaine use has declined across most age groups, federal data indicates a concerning rise in adolescent use. Among individuals aged 12 to 17, past-year cocaine use tripled from 0.1 percent in 2021 to 0.3 percent in 2024, representing an increase from approximately 24,000 users to 72,000. This demographic shift is notable, as adolescent use had been historically low.
Researchers have not specified what constitutes a 'dose' of cocaine in the study. Further investigation is needed to determine the longevity of these genetic changes and how they precisely translate to addiction risk.