By Gene Emery

NEW YORK (Reuters Health) - Like conventional cigarettes, electronic cigarettes may function as a "gateway drug" that can prime the brain to be more receptive to harder drugs, U.S. researchers said on Wednesday.

The findings, published in the New England Journal of Medicine, add to the debate about the risks and benefits of electronic cigarettes, the increasingly popular devices that deliver nicotine directly without burning tobacco.

"With e-cigarettes, we get rid of the danger to the lungs and to the heart, but no one has mentioned the brain," coauthor Dr. Eric Kandel of Columbia University, whose findings were published in the New England Journal of Medicine, said in a telephone interview.

In laboratory studies, the researchers showed that "once mice and rats are on nicotine, they are more addicted to cocaine" after being introduced to that drug, said Dr. Aruni Bhatnagar of the University of Louisville, who was not involved in the study but chaired a 10-member American Heart Association panel on the impact of e-cigarettes.

That was true even when the mice received nicotine without burning tobacco, Kandel, a 2000 Nobel laureate for his work on memory, told Reuters Health in a telephone interview.

The findings by Kandel and his wife, Columbia University researcher Denise Kandel, expand on her earlier work on nicotine as a "gateway drug," a theory she first reported on in 1975.

"E-cigarettes have the same physiological effects on the brain and may pose the same risk of addiction to other drugs as regular cigarettes, especially in adolescence during a critical period of brain development," they wrote.

Although it is not yet clear whether e-cigarettes will prove to be a gateway to the use of conventional cigarettes and illicit drugs, they said "that's certainly a possibility."

"Nicotine clearly acts as a gateway drug on the brain, and this effect is likely to occur whether the exposure comes from smoking cigarettes, passive tobacco smoke, or e-cigarettes," they wrote.

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Electronic cigarettes are now a $3 billion business with 466 brands that include candy flavoring and are increasingly popular among children, according to the World Health Organization.

Using 2004 epidemiologic data from a large, longitudinal sample, Denise Kandel found that the rate of cocaine dependence was highest among users who started using cocaine after having smoked cigarettes.

Dr. Shanta Rishi Dube of the Georgia State University School of Public Health, who was not involved in the research, said the results "appear valid based on prior studies that have looked at nicotine as a potential gateway (drug)."

Bhatnagar said the findings strengthen the case for regulation of e-cigarettes by the U.S. Food and Drug Administration.

"If we don't have strict laws on youth access and marketing for e-cigarettes, we may fuel an entire new generation of people on nicotine, and that will be a gateway drug for the use of other drugs," Bhatnagar said.

SOURCE: http://bit.ly/1tlTbJx; New England Journal of Medicine, N Engl J Med 2014

(Reporting by Gene Emery; Editing by Julie Steenhuysen and Ken Wills)