Addiction-Boosting Compounds Added to 'Light' Cigarettes

Fran Lowry

June 10, 2015

The tobacco industry adds chemicals to its products to make them more irresistible to consumers and thwart smokers' efforts to quit, new research suggests.

Pyrazine additives to low tar, or "light," cigarettes and e-cigarettes are reinforcing the addictive qualities of nicotine and should be regulated by the US Food and Drug Administration (FDA), investigators led by Hillel R. Alpert, ScD, Harvard School of Public Health, Boston, Massachusetts, conclude.

"Pyrazine compounds used as additives in tobacco products appear to enhance addiction by increasing product appeal and making it easier for nonsmokers to initiate smoking, more difficult for current smokers to quit, and much easier for former smokers to relapse into smoking," Dr Alpert told Medscape Medical News.

"Tobacco is one of the most powerfully addictive substances of abuse known. While tobacco dependence is understood to be primarily caused by nicotine, nicotine's reinforcing effects are not sufficient to account for the intense addiction and high relapse rates among smokers after quitting, even when nicotine is provided in forms other than tobacco," Dr Alpert said.

The study was published online June 10 in Tobacco Control.

Inside the Tobacco Industry

The investigators researched internal tobacco industry documents made public as a result of the Master Settlement Agreement of 1998, in conjunction with research of the published scientific literature on the composition and role of cigarette additives.

Tobacco manufacturers developed the use of a range of compounds, including pyrazines, in order to enhance "light" cigarette products' acceptance and sales, which had been declining as health concerns about smoking began to surface.

The additives enhance the taste, aroma, and flavor of these low-tar products, but they also have other effects.

"We conducted this study to better understand tobacco manufacturers' research and development of the use of nonnicotine additives and ingredients that contribute to the increased appeal, attractiveness, and addictiveness of products," said Dr Alpert.

"Flavor additives such as pyrazines have chemosensory and pharmacological effects and may enhance tobacco dependence by acting independently as well as synergistically with nicotine. Pyrazines are now incorporated as constituents in the liquid flavor formulations of e-cigarettes, whose use has been increasing rapidly and dramatically among youth," he added.

Super Juice

The researchers unearthed documents that revealed that Philip Morris searched for ways to develop cigarettes with very low tar yields but with a taste and flavor that would satisfy smokers' "palates and needs."

The company discovered the components associated with the strongest odor intensity from the many aromatic chemicals and substances in regular tobacco smoke and then made synthetic versions for use in low-tar cigarettes.

It came up with the MERIT brand, the first low-tar cigarette, yielding less than 9 mg of tar.

Philip Morris called its new flavor formulation "Super Juice." It contained three pyrazines (2,6-dimethyl pyrazine, tetramethyl pyrazine, and trimethyl pyrazine) as well as acetic acid, cyclotene, maltol, isobutyric acid, and 1-methyl indole.

MERIT brands, which include Marlboro and Marlboro Lights, were found to contain at least six pyrazines (2-methylpyrazine, methylethylpyrazine, dimethylethylpyrazine, 2,3-dimethylpyrazine, 2,6- dimethylpyrazine, trimethylpyrazine, and tetramethylpyrazine).

In the late 1970s, Super Juice–like compounds were added to Marlboro Lights, now known as Marlboro Gold, which has become the leading selling cigarette brand.

Dopamine Release

"Pyrazines contribute to the burley flavor, which is a common characteristic of many Philip Morris brands," Dr Alpert said.

Pyrazines are also known to act on sensory receptors. When the researchers trolled the tobacco industry documents, they found that the industry had identified a role for pyrazines in smoothing, which made inhaling, uptake, and delivery of nicotine easier by curbing the harshness and irritation caused by smoking.

The documents also revealed that the tobacco industry believed additives could promote high consumer acceptance and continued use of their products.

In 1986, a report by RJ Reynolds described its campaign to target 18- to 24-year-old men by increasing the smoothness and masking the harshness and irritation of tobacco smoke.

Pyrazines stimulate receptors in the lining of the nose, which may enhance learned behavior, either by acting alone or in combination with other sensory stimuli. Also, several pyrazine derivatives may have a role in increasing the amount of dopamine released during smoking, which is an effect that is independent of nicotine, Dr Alpert said.

"The sensory inputs of pyrazine flavor additives might also provide cues for reward-related learned behaviors and could play a critical role in the development, maintenance, and relapse of tobacco dependence. They could increase the attractiveness of smoking, particularly among youth," Dr Alpert said.

"Currently, the FDA bans the use of certain flavor additives at characterizing levels in cigarettes only. A distinction should be made between characterizing flavors with primarily taste effects (eg, chocolate, licorice) and those with primarily chemosensory (eg, cooling, tingling, smoothing) effects," Dr Alpert said.

"Regulators around the world should consider regulating the use of pyrazines and other similar ingredients in both cigarettes and e-cigarettes," he said.

Kudos

Commenting on the study for Medscape Medical News, Shawn L. Cassady, MD, from Key Point Health Services, Aberdeen, Maryland, said it has been long known that artificial ingredients have been added to cigarettes to enhance flavor and addictive potential.

"This paper elucidates the industry's evolution from the simple addition of pyrazines, for their characteristic 'nutty' flavor, to the crafted manipulation of chemoreceptors to drive human behavior," Dr Cassady said.

"We applaud the authors' high standard of medical investigative journalism. If only we had similar exposés on the multitudes of other chemoreceptor manipulations to which we are currently subject. In a profit-driven, consumer economy, without checks and balances on human health, addictive products win," he said.

This research was supported by the National Cancer Institute. Dr Alpert and Dr Cassady report no relevant financial relationships.

Tob Control. Published online June 10, 2015.

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