According to the National Institute of Drug Abuse (NIDA), part of the National Institute of Health, scientists have identified a biological mechanism in a landmark study in mice, which could provide insight into how tobacco products could act as gateway drugs, and therefore increase the risk of abusing cocaine and perhaps also other drugs. The study, published in today’s Science Translational Medicine is the first study that shows that nicotine might prime the brain to enhance the behavioral effects of cocaine.

Researchers based their gateway drug model on epidemiological evidence on reports of most illicit drug users who state they used tobacco products or alcohol before using illicit drugs. Over the years, this model has generated substantial controversy, mainly over whether prior drug exposure to nicotine, alcohol or marijuana is causally associated with later drug abuse. Until recently, scientists have not been able to demonstrate a biological mechanism whereby nicotine exposure could increase vulnerability to illicit drug use.

In the new study researchers at Columbia University in New York City administered nicotine to mice’s drinking water for a minimum of seven days and discovered they displayed an increased response to cocaine. This priming effect was based on the nicotine’s effect on gene expression that was previously not recognized; Nicotine changes the structure of the tightly packaged DNA molecule and reprograms expression patterns of specific genes, in particular that of the FosB gene, which has been associated with addiction, and ultimately changes the behavioral response to cocaine.

The researchers wanted to assess if their study results paralleled findings in humans by re-examining statistics from the 2003 National Epidemiological Study of Alcohol Related Consequences. It enabled them to investigate the link between onset of nicotine use and degree of cocaine dependence where they discovered that the rate of cocaine dependence was higher among cocaine users who smoked prior to starting cocaine compared with those who tried cocaine prior to smoking.

If the outcome in mice would display similar effects in humans, the researchers suggest, that effective smoking prevention efforts would not just prevent negative health consequences linked to smoking but could also lower the risk of progression and addiction to cocaine and possibly other illicit drug use. Researchers continue to use the mouse model to provide a new mechanism to investigate the gateway theory from a biological perspective.

Senior author Eric Kandel, M.D., of Columbia University Medical Center concludes:

“Now that we have a mouse model of the actions of nicotine as a gateway drug this will allow us to explore the molecular mechanisms by which alcohol and marijuana might act as gateway drugs. In particular, we would be interested in knowing if there is a single, common mechanism for all gateway drugs or if each drug utilizes a distinct mechanism.”

For more information on nicotine and cocaine, please visit and

The study, and a perspective by NIDA Director Dr. Nora D. Volkow, can be found online here.

Written by Petra Rattue