UCLA to Test Citric Inhalant in Smoking Study

A fine mist formed from a chemical common to lemon and orange juice that may be a radically different stop-smoking approach is being readied for a large-scale trial at UCLA sometime early next year.

In a newly published study, researchers say preliminary testing of the mist-inhaler shows it has promise as a way to substitute the slightly irritating sting of citric acid for the so-called “taste” of tobacco.

And if the early promise is borne out by the larger study, a combination therapy mating nicotine absorbed through the skin from a stick-on patch with puffs on a cigarette-shaped mist inhaler could be an aid to help millions of people who can’t kick their smoking addictions now, local and national experts believe.

The citric acid mist technique for smoking treatment is described this month in the journal Chest in an article by UCLA tobacco researchers Jed Rose and Carol Hickman who started working on the theory when they questioned a basic tenet of tobacco treatment theory--that it is nicotine, alone, that determines the addiction. The journal is the official publication of the American College of Chest Physicians.

‘Taste’ of Tobacco

Earlier smoking treatment studies had relied in part on blunting taste-like sensations in smoking--by such techniques as anesthetizing smokers’ throats--to focus on the chemical action of nicotine. The theory was that tobacco addiction is controlled by the direct effects of nicotine on the brain--just as other addictions are governed by narcotics and stimulants influencing brain activity.

But to Rose, who headed the new study, nicotine represents only one element in the total smoking equation. It is this complexity that has led a variety of nationally known experts to suggest that the addiction to tobacco is the most difficult of all drug dependencies to treat.

In an interview earlier this week at the Veterans Administration Westside complex, where he maintains an office and a cigarette-smoking research laboratory, Rose said he came to suspect that the complex of sensations that are lumped together in what is commonly called tobacco “taste” may actually play more of a role than the chemical action of nicotine in some people. The craving for the gratification of taste is not satisfied by simply sucking on lollipops since the sensations in the mouth, throat and lungs of inhaling smoke still lack.

To test the theory, Rose and Hickman developed a fine mist of citric acid that is inhaled by smokers and that mimics the irritation capability and taste components of tobacco smoke. With their olfactory senses artificially blocked--so they could not smell the difference between tobacco and the lemon-like odor of citric acid--15 smokers reported they found citric acid somewhat less satisfying than their favorite brands of cigarettes but more satisfying than low-tar cigarette brands they also smoked for the research study.

The potential usefulness of citric acid could represent a major advance over smoking cessation programs that rely on such things as nicotine gum, because citric acid has no known harmful effects on the body while treating tobacco addiction with a nicotine substitute is a technique analogous to supplying heroin to junkies.

It is the findings of that first study, just published, that triggered what Rose and Hickman say will be a new test of a far more sophisticated type of inhaled citric acid--probably to be mated with use of a stick-on patch that permits measured doses of nicotine to be absorbed through the skin. While the new acid inhalers have not yet been finally designed, Rose said they will look something like a cigarette and will permit a smoker to do the equivalent of puffing to draw in small doses of a new type of mist whose particles are so small the tell-tale lemon flavor cannot be detected.

If all goes well, said Rose, the new technique could be “a useful crutch, or weaning tool, for smokers. Nicotine is just one part of the smoking dependence process. This is one of the reasons for only a partial success of programs that use nicotine gum.”

Nicotine Substitution

Existing smoking treatment theories that rely on nicotine substitution assume that failures in treatment occur because sufficient amounts of nicotine are not getting in the bloodstreams of smokers. But Rose has another idea.

“A more likely explanation for partial or incomplete success of nicotine replacement therapy,” he said, “is that it often lacks the unique sensations of smoking.”

Rose said he hopes to enroll 160 people in the new study--80 assigned to a group that will test the new mist inhaler and nicotine patch technique and 80 others who will use less advanced smoking cessation methods.

Several pitfalls remain before the study can begin, Rose said. For instance, the U.S. Food and Drug Administration has yet to approve the stick-on nicotine patch and final design of the inhaler has not been determined.

What Rose suspects is likely to emerge from the new study is an impression that tobacco addiction is really a mix of several different conditions. “It may be that one could classify smokers into groups,” he said. “There may be smokers for whom the nicotine is the primary factor. A (skin-mounted nicotine) patch may be all they need.

“Other smokers may have their biggest problem with the craving for the smoking sensation (for whom just substituting citric acid mist inhalation can successfully treat the smoking problem.) And then there might be a group for whom a combination of both might be appropriate.”

Other Experts

The theory has already struck other experts as suggesting a possibly promising new technique for treating tobacco addiction. Jack Henningfield, of the addiction research center of National Institute on Drug Abuse in Baltimore, said the new UCLA study may point the way to a promising new method to help smokers.

“I think what we’re finding out is that there are some powerful determinants of cigarette smoking that we don’t understand very clearly,” Henningfield said in a telephone interview. In an editorial accompanying the new medical journal report, Henningfield wrote that the technique proposed by Rose “is potentially a significant advance for alleviation of urges to smoke and, thus, for the treatment of cigarette smoking.”

“It’s safe to say that three quarters of smokers have some level of physical dependence to nicotine,” Henningfield said, “and they will experience some kind of nicotine withdrawal when they quit, but even in those people, the intensity of the withdrawal is going to differ widely.

“Here is where nicotine and a lot of other drugs differ. What’s different about nicotine is that you’re never more than five minutes away from a cigarette. You may be dealing very well with your withdrawal and you have a short, strong craving (for the taste sensation of the smoke).

“For that kind of person, the availability of some other way of satisfying that need could be very useful. You might keep with you some device that would provide some momentary pleasure to reduce the craving and then you’d be just fine.”