Even a single exposure to cocaine may trigger profound changes in brain cells that persist for at least two weeks, according to research presented at FENS Forum 2026, the meeting of the Federation of European Neuroscience Societies, as reported by Medical Xpress.
According to the researchers, the findings help explain why addiction can begin to develop in some individuals after only a few episodes of cocaine use.
Cocaine is one of the most dangerous psychostimulant drugs. It is highly addictive and can cause anxiety, paranoia, cardiovascular complications, impaired mental health, and a range of other serious health consequences.
According to the United Nations Office on Drugs and Crime (UNODC), approximately 25 million people worldwide currently use cocaine—the highest number ever recorded.
The study was led by Professor Ana Pombo of Johns Hopkins University, who also heads a research group at the Max Delbrück Center for Molecular Medicine in Berlin. The researchers sought to determine what happens inside brain cells following the very first exposure to cocaine and how these changes might contribute to addiction months or even years later.
The experiments were conducted in mice using an advanced genome architecture mapping technique. Rather than examining DNA sequence alone, this method reveals the three-dimensional organization of DNA within the cell nucleus. The spatial arrangement of genetic material plays a crucial role in determining which genes are switched on or off.
The team focused on dopaminergic neurons in the ventral tegmental area (VTA) of the midbrain—a key region involved in reward processing, motivation, and the development of addiction.
The researchers found that just 24 hours after cocaine exposure, the three-dimensional genome architecture of these neurons had changed substantially. Even more strikingly, many of these alterations persisted for at least two weeks, and some became even more pronounced over time.
Specifically, a single dose of cocaine generated approximately 1,700 new chromatin regulatory regions involved in controlling gene activity, while around 1,100 existing regulatory regions disappeared. Such extensive remodeling has the potential to fundamentally alter how neurons function.
Further analysis revealed corresponding changes in gene expression. The affected neurons began producing higher levels of several neuropeptides—signaling molecules that have previously been linked to substance use disorders in humans. At the same time, the activity of genes involved in maintaining normal neuronal function declined.
According to the authors, these findings point to a molecular "scar" that cocaine leaves within the genome of brain cells. This long-lasting reorganization may prime the brain to respond more strongly to future cocaine exposure, thereby increasing susceptibility to addiction.
The researchers caution that it remains unknown whether these genomic changes are permanent or whether neurons are eventually able to recover completely. Further studies will also be needed to determine how directly these molecular alterations influence addiction risk in humans.
Commenting on the findings, Professor Christina Dalla of the National and Kapodistrian University of Athens, who was not involved in the study, said the results challenge the common belief that occasional or one-time cocaine use is harmless.
According to Dalla, even a single exposure may trigger long-lasting changes in brain cells that could increase an individual's vulnerability to developing addiction later in life.
The authors emphasize that the study was conducted in laboratory mice, and the findings must be confirmed in further research involving humans.
Nevertheless, the results provide new insights into the molecular mechanisms underlying addiction and may ultimately contribute to the development of more effective strategies for its prevention and treatment.
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