New research presented at the Federation of European Neuroscience Societies (FENS) Forum 2026 in Barcelona suggests that just one exposure to cocaine can change brain cells in ways that last for at least two weeks, at least in mice.
Cocaine is a highly addictive drug linked to anxiety, paranoia, heart problems, and long-term mental health issues. According to the UN Office on Drugs and Crime, an estimated 25 million people worldwide currently use it.
The research was presented by Ana Pombo, a Guest Group Leader at the Max Delbrück Centre for Molecular Medicine in Berlin. As she put it, “We know that cocaine hijacks the reward machinery of the brain.” She explained that most people don’t become addicted the first time they try cocaine, but many do after using it a second time or repeatedly, and that scientists still don’t fully understand what’s happening inside brain cells during that process, or whether the effects stick around. Her team has been studying mice to figure out where the brain “stores” the memory of a first cocaine exposure, and why addiction can develop even when someone’s drug use is spread out over months or years.
Rewiring the Genome
To investigate this, Pombo’s team used a technique called genome architecture mapping, which allows scientists to study how genetic material is physically organized inside a cell. This 3D organization matters because it can determine whether certain genes get switched on or off.
The researchers focused on dopaminergic neurons in a part of the mouse midbrain called the ventral tegmental area, a region known to play a central role in reward and motivation. Compared to mice that hadn’t been exposed to cocaine, these neurons showed major changes in how their genetic material was organized. The changes appeared within 24 hours of exposure, and some had actually grown stronger after two weeks.
Specifically, the researchers found that a single dose of cocaine triggered the formation of around 1,700 new “insulation areas” in the genome, structures that help control gene activity, while roughly 1,100 existing ones disappeared.
Looking closer, the team found that cocaine-exposed brain cells produced more of certain signaling molecules called neuropeptides, which have previously been linked to addiction in humans. Meanwhile, other genes responsible for normal cell function became less active.
Pombo suggested that a single hit of cocaine appears to “rewire” the genome of these important brain cells, and that the scale and persistence of these changes, still visible after two weeks, was unexpected. She described it as the drug leaving a kind of longer-term scar on the genome. These lasting changes might prime the brain to respond more strongly to a second dose, which could help explain why repeated cocaine use raises the risk of addiction. However, important questions remain unanswered, including whether these changes are permanent or whether brain cells can eventually recover, and how directly they translate into addiction risk.
A Warning Against “Harmless” Recreational Use
Professor Christina Dalla of the National and Kapodistrian University of Athens, who wasn’t involved in the study, said, “Cocaine use is a serious and growing problem around the world.” She noted that studying addiction mechanisms directly in human brains is extremely difficult, which is why researchers rely on animal models like mice. Dalla said the study reveals significant, lasting changes in mouse brain cells after only one exposure to cocaine, showing that the drug can alter the genome’s structure in ways that persist over time. She added that this challenges the assumption that occasional recreational cocaine use is harmless, since even a single use could alter the brain and increase future addiction risk. She suggested that further research into these changes could help explain why some people are more prone to addiction than others, and ultimately support the development of new treatments.