IS NICOTINE WITHOUT THE SMOKE OK?

For 55 years, Clarence Heidemann couldn't imagine life without cigarettes.
Then in 1991 he kicked the habit with the help of nicotine gum, which his
doctor told him would help him over the biggest hurdle: the crucial first
weeks when the vast majority of would-be quitters relapse.

Seven years after he traded two or three packs of cigarettes each day for a
dozen pieces of the gum called Nicorette, the retired paper-mill manager
finds himself saddled with another habit he'd like to break. "I don't think
I'm addicted to it," said Heidemann, who chomps on the bitter, dun-colored
gum every day. "But it's certainly become a habit."

Heidemann, it seems, has plenty of company, although there's no way to know
for certain how many ex-smokers use nicotine gum or nicotine patches for
months - or years - longer than the six to 12 weeks approved by the Food
and Drug Administration.

But a federally funded study of 6,000 current and former smokers has found
that 19 percent were still chewing the gum after five years, with no
apparent ill effects.

Heidemann, 75, who lives in Valdosta, Ga., said his doctor is not concerned
about his continued reliance on nicotine gum. "He said it's not harmful and
it's better than smoking."

The view that nicotine, when it is not smoked, is a relatively benign and
possibly beneficial drug is gaining acceptance among scientists as well as
physicians, particularly those who run smoking-cessation programs. This
dramatic change in attitude has ushered in new and sometimes-controversial
approaches to treating smokers.

While most users of the gum and the patch manage to wean themselves from
nicotine, others seem unable to do so. As a result, many experts now
contend that for the most addicted, nicotine maintenance appears to be a
more-realistic goal than abstinence.

They point to a growing body of research that shows that prolonged and,
especially, heavy use of tobacco appears to change the makeup of the brain,
resulting in the proliferation of nicotine receptors. These receptors are
responsible for the sense of pleasure and improved concentration that
smokers report from having a cigarette.

Some believe it's more realistic to persuade hard-core smokers to use
nicotine substitutes at least some of the time; that could eventually
motivate them to quit and, in the meantime, reduces their exposure to
cigarettes.

But among the concerns about this controversial approach is whether telling
smokers they should cut down will undermine the drive to get them to quit
altogether. The other problem is the lack of evidence that cutting down but
not quitting results in a lower risk of mortality or illness.

Not a carcinogen

Although nicotine is the ingredient that makes cigarettes so addictive, it
is not what makes them so deadly.

Unlike cigarette tars that contain dozens of cancer-causing chemicals,
nicotine is not a carcinogen, contrary to popular belief. People who use
nicotine-replacement products - the gum, patch, nasal spray or inhaler -
also do not ingest carbon monoxide, as do smokers.

"Most patients and their physicians don't understand the difference between
nicotine dependence and tobacco dependence," said David Sachs, who directs
the Palo Alto (Calif.) Center for Pulmonary Disease Prevention, which tests
smoking-cessation treatments for drug companies.

"Nicotine dependence is clearly the major physiological driving force
behind cigarette smoking, but it's tobacco dependence that kills," added
Sachs, a clinical associate professor at Stanford University School of
Medicine.

"Nicotine in replacement products is a much safer substance, and generally
people take in less nicotine anyway," agreed Neil Benowitz, a professor of
medicine and psychiatry at the University of California, San Francisco, and
one of the scientific editors of the landmark 1988 surgeon general's report
on nicotine addiction and smoking. Benowitz and other experts cautioned
that while nicotine in replacement products seems fairly harmless, it can
raise the heart rate, as does smoking.

Furthermore, nicotine's effect on fetal development, nursing infants or
people with certain heart problems is unknown. Like all drugs, Benowitz
noted, nicotine-replacement treatments have risks, "but I think the risks
are probably small."

This kinder, gentler view of nicotine, coupled with attempts to expand use
of nicotine-replacement drugs, possibly by relabeling them for longer use,
is an exquisitely sensitive subject for drug companies.

While eager to increase the market for nicotine products, they are loath to
be seen as encouraging and especially profiting from smoking, a habit that
is linked to more than 400,000 deaths in the U.S. annually. Last year
nicotine-replacement products accounted for $350 million in sales,
according to IMS Health, a health-care information company. By contrast,
annual U.S. cigarette sales total at least $25 billion.

Officials of SmithKline Beecham, the industry leader that markets
Nicorette, the only brand of nicotine gum available, and the most popular
of the four patches, Nicoderm, declined to be interviewed.

In a prepared statement, spokeswoman Nancy Lovre said SmithKline Beecham's
goal is"helping people become smoke- and nicotine-free."

Ron Schmid, a spokesman for McNeil Consumer Products Co., which markets the
Nicotrol patch, said that "while it's not approved for longer than six
weeks, we've noticed no health hazard from longer use. Some people may need
longer therapy to break the habit and satisfy their cravings."

Going cold turkey

Most people who try to quit still use the old-fashioned and least-effective
method: They go cold turkey. Nearly half relapse within the first 48 hours,
while 66 percent don't last a week, according to addiction expert John
Hughes, a professor of psychiatry at the University of Vermont School of
Medicine.

Those who use the gum, patch or another form of nicotine replacement
increase their chances of quitting from about 5 percent to between 10 and
20 percent, depending on their motivation and other factors. Those highly
motivated who use nicotine-replacement products along with supportive
counseling raise their chances to about 30 percent.

Smokers typically quit five to 10 times before staying smoke-free.

Every year, according to federal statistics, about 1.2 million Americans
stop smoking. The number and prevalence of ex-smokers has risen
dramatically in the past 20 years. Currently, about 25 percent of American
teenagers and adults smoke, while 25 percent are ex-smokers and 50 percent
never smoked. In 1976, nearly 37 percent of the population smoked.

Not everyone who smokes regularly is addicted to nicotine, experts say.
Sachs estimates that 90 percent of the nation's 46 million smokers are
addicted and their dependence ranges from mild to severe.

Smokers with mild addictions - or none at all - are among the minority of
users who can quit without the cravings, depression, anxiety or
irritability that more addicted users typically report; they don't need to
regularly ingest nicotine.

There may be a biological reason for this. A study by University of Toronto
researchers published earlier this year in the journal Nature has found
that some people carry a genetic variant in a liver enzyme that may protect
them from nicotine addiction. People with this genetic variant appear to
metabolize nicotine more slowly and usually smoke fewer cigarettes than
those without it.

Safe substitutes

Few side effects, none of them serious or permanent, have been reported
with the gum or patches, which account for more than 90 percent of the
nicotine-replacement market. The deliberately bad taste and texture of the
gum - combined with the price and prohibition on sales to anyone under 18 -
have helped discourage abuse by teenagers, FDA officials say.

The chances of abuse were always considered small because both products
release nicotine far more slowly than do cigarettes.

Nicotine is not instantly addicting. One study estimated that it takes
about 100 cigarettes to become hooked.

In 1996 the FDA approved two other forms of nicotine treatment that are
available only by prescription. They are a potent nasal spray, which
delivers nicotine within a few seconds, and an inhaler, which resembles a
cigarette. The inhaler allows users to draw nicotine into their mouths,
where it is absorbed; most of it never reaches the lungs.

The inhaler is being test marketed in Baltimore and Houston and has one
feature that may appeal to some smokers. It relies on the hand-to-mouth
movement that a pack-a-day smoker is estimated to repeat 73,000 times a
year. The desire to handle cigarettes is believed to be an important reason
for smoking; such behaviors are characteristic of other forms of drug
abuse.

Although there were reports of abuse of the nasal spray during clinical
trials - some participants overused the spray even after they developed
painful nasal ulcers - none has surfaced subsequently, according to the
FDA.

There is a fifth alternative, an antidepressant called Zyban approved last
year for smoking cessation treatment. The drug, also known as Wellbutrin
SR, contains no nicotine but has been effective in fighting smoker
cravings.

The cost factor

One barrier to wider use of nicotine replacement may be cost.

In an article published last winter in the journal Tobacco Control,
psychologist Saul Shiffman of the University of Pittsburgh's Smoking
Research Group found that since 1996, when the FDA approved
over-the-counter sales of the patch and gum, sales have jumped 152 percent;
the change from requiring a doctor's prescription is expected to result in
114,000 to 304,000 new ex-smokers annually.

But Schiffman and his co-authors estimated that further improving access
could reduce the numbers even more. They noted that the daily cost of using
the gum or the patch is equivalent to a cigarette habit of a pack and a
half a day, and may especially deter low-income smokers, who increasingly
account for the majority of cigarette users.

Meanwhile, drug companies are competing to develop new treatments designed
to appeal to smokers looking for help quitting. At least half a dozen
products - including a nicotine lozenge, a reusable lollipop and a
triple-strength patch - are being tested.

"Every new product adds another weapon to our armamentarium," says nicotine
expert Jack Henningfield, formerly with the National Institute on Drug
Abuse.

"With nicotine gum, we're probably where we were decades ago when
penicillin was invented."

Checked-by: Joel W. Johnson