About 40 percent of America’s 50 million smokers will try to kick the habit at least once this year, according to the federal Centers for Disease Control and Prevention (CDC). On each attempt, fewer than one in 10 will succeed. As discouraging as those numbers may seem, nicotine addiction researchers offer the offsetting news that those very failures pave the road for breaking dependence on tobacco — something that about half of
smokers ultimately achieve, according to federal treatment guidelines.

“Most people have to try to quit probably five to seven times before they succeed,” said John Hughes, professor of psychiatry at the University of Vermont. “It’s just like swimming — it’s important to keep jumping in the water to learn.”

And as experts like to note, there has never been a better time to quit — or so many different scientifically validated options to help smokers reduce the pangs of nicotine withdrawal and the craving for cigarettes, both of which make quitting smoking harder than making most other behavioral changes. (To help prompt smokers to make the effort and to limit exposure of non-smokers to cigarette smoke, 82 percent of work sites in the District are smoke-free, 43 states restrict smoking in government offices and 21 restrict smoking in private work places, according to the CDC.)

Ten years ago, “all we had to offer was going cold turkey or nicotine gum,” says Michael C. Fiore, chairman of a federal panel that issued treatment guidelines two years ago calling for nearly every smoker who wanted to quit to use medications to support their efforts. Today, there are seven drug treatment choices, as well as many organized smoking cessation programs and individual counseling services that also boost chances that smokers will manage to quit.

Four safe and proven nicotine replacement methods — gum, a patch that delivers nicotine through the skin, an inhaler that mimics the effect of smoking and a spray that provides a quick burst of nicotine to nasal passages — can deliver gradually declining doses to take the edge off cravings and withdrawal. They have only minimal side effects, a very low risk of addiction and are free of the nearly 4,000 harmful substances that cigarette smoke delivers.

The treatments don’t end there. An antidepressant medication — bupropion, marketed for depression under the brand name Wellbutrin and for smoking cessation as Zyban — can also help break cigarette addiction, though the scientific process by which this occurs is still not understood.There have been many reports of serious adverse effects, including some deaths, from Zyban in Europe. Next week, several professional societies will review the data. But for now, “it’s unclear if the events are related to the medication,” says Hughes.

Two other options for especially difficult cases of smoking addiction are the blood pressure medication clonidine and the antidepressant nortriptyline. While the evidence of their value is not as extensive as that for nicotine replacement drugs, a government panel advised recently that these medications be tried if other drugs have failed. (Neither, however, is approved for this use by the Food and Drug Administration).

“The good news for smokers,” Fiore says, “is that people now have a choice. There’s never been a better time to quit.”

Trouble is, a lot of smokers do it the wrong way and increase their odds of failure. Since smoking is often viewed as a weakness or character flaw, many smokers tend to tough it out themselves and go cold turkey. Or they mistakenly use minimal amounts of the nicotine replacement drugs and other medications that are proven scientifically to help assuage the strong physiological symptoms of withdrawal.

“That is why there is such a high relapse rate,” explains David Sachs, clinical associate professor of pulmonary and critical care medicine at Stanford University School of Medicine in California. “It’s like killing all four engines on a Boeing 747 where you’re 2,000 feet above the runway. You crash and burn and then people start beating up on themselves. They say, ‘I am a failure,’ when they are really dealing with something that has a striking rationale as far as pharmacology and physiology are concerned.”

“Well, I am back again. They say that the third time’s a charm. Hope they are right. This is the third time this year that I am quitting. The last time I went back to smoking, I got so depressed that I didn’t want to talk to anyone for a long time. Can’t say I will make it, can’t say I won’t. I’m just going to take this one minute, hour and day at a time.”

— posting from a smoker planning to give up cigarettes on Feb. 13.

No one suggests that quitting is easy, even with nicotine replacement medications. Adult smokers go through an average of a pack of cigarettes each day. At 20 cigarettes per pack and 10 puffs per cigarette, that’s 200 nicotine hits a day right to the brain, making smoking “one of the world’s most intense habits,” says the University of Vermont’s Hughes.The cigarette is one of the fastest and most powerful drug delivery systems ever known.

“It takes just a few heartbeats to get nicotine from the tip of your finger to the brain,” says Richard Hurt, director of the Nicotine Dependence Center at the Mayo Clinic in Rochester, Minn. Once there, nicotine produces significant changes in brain cells. Chemically similar to naturally occurring neurotransmitters or chemical messengers, nicotine displaces some brain chemicals. Just 10 days of smoking triples the number of entry points — receptors — that allow nicotine to get inside brain cells, says Stanford’s Sachs.

There, nicotine acts on the pleasure-reward pathway by raising levels of four key neurochemicals that affect alertness, energy and mood — dopamine, norepinephrine, beta endorphins and serotonin. (Newer antidepressant medications target levels of these same brain chemicals.) “The bottom line is that nicotine has a lot of very beneficial effects on how we feel and think,” Sachs says.

That’s why the development of effective nicotine replacement drugs has finally given an edge to smokers who want to quit. Using one or more of these medications boosts success rates to about 25 percent, the federal treatment guidelines issued in 2000 by the Agency for Healthcare Research and Quality (AHRQ) found. Evidence suggests they could go higher if more intensive treatment and greater support were applied.

Close monitoring of withdrawal symptoms and tailoring nicotine replacement therapy to the individual has produced success rates of up to 50 percent at some of the best smoking cessation programs.

At Mayo’s Nicotine Dependence Center, for instance, smokers pay $3,300 each to check into an intensive, weeklong residential smoking cessation program. They undergo blood testing for cotinine, a marker of nicotine byproducts; the tests are used to help adjust treatment individually for withdrawal symptoms and cravings. The program includes daily group and individual therapy, stress reduction, nutrition and diet information, supervised exercise and a 12-step program similar to Alcoholics Anonymous.

About 700 smokers have gone through the decade-old program, which attracts long-term older smokers — average age 53 compared with early f