Home > Encyclopedia of Drugs, Alcohol, and Addictive Behavior > Nicotine Delivery Systems For Smoking Cessation

Nicotine chewing gum.

Nicotine chewing gum was the first alternative nicotine delivery system to be approved as a smoking cessation aid. Nicotine is contained in a gum resin and is slowly released upon chewing. Nicotine gum is available in two strengths, containing either two milligrams or four milligrams of nicotine. Of that amount, about half is released on chewing, which is comparable to the amount of nicotine delivered from one or two cigarettes. Unlike cigarette smoking, which delivers the nicotine rapidly into the bloodstream through the lungs, nicotine from the chewing gum is slowly absorbed through the cheeks. Most of the nicotine that is swallowed does not reach the general circulation, because after being absorbed from the small intestine, it is destroyed as it passes through the liver. The use of nicotine gum has been shown to double success rates in smoking cessation. Problems with the gum include unpleasant taste, jaw soreness, stomach upset from nicotine that is swallowed, and inconsistent levels of nicotine in the bloodstream.

Nicotine skin patches.

Partly to overcome the unpleasant side effects of nicotine chewing gum, nicotine skin patches were developed to release a controlled amount of nicotine directly through the skin. Nicotine is easily absorbed through the skin, and it is possible to provide a steady delivery of approximately 21 to 22 milligrams per day, equivalent to the amount of nicotine delivered from about twenty cigarettes (one pack). However, as with nicotine chewing gum, the nicotine is delivered much more slowly than from cigarettes, and the peak blood levels are thus lower than those obtained from cigarettes. The patches are applied once a day, and after using full-strength patches for at least 4 weeks, reduced-strength weaning patches can be used to gradually withdrawal from nicotine. Use of the patch has been shown to double or triple success rates in quitting smoking; a small proportion of patients (less than 10%) do experience skin irritation from wearing the patches.

Nicotine nasal spray.

Some researchers have speculated that a more rapid absorption of nicotine than is achieved with patches or gum would more closely simulate the effects of cigarettes desired by smokers and increase success rates in smoking cessation. A nicotine nasal spray is available for smoking cessation treatment; it delivers 1 milligram of nicotine (equivalent to the delivery of a typical cigarette) with each use (one spray per nostril). Unlike other modes of NRT, the nasal spray delivers nicotine to the bloodstream very rapidly, within a few minutes. Some studies have suggested the nasal spray might be particularly advantageous for more highly dependent smokers. Problems with the spray include local irritation caused by nicotine, which can result in sneezing, a runny nose, watering eyes, and a cough.

Nicotine inhaler.

A fourth mode of NRT resembles a cigarette in size and shape, and releases a nicotine vapor when a smoker puffs on it. However, the dose of nicotine released in each puff, which is limited by the vaporization of nicotine at room temperature, is much less than with cigarette smoking. Intensive use (eighty inhalations over 20 minutes) releases, on average, 4 milligrams of nicotine, of which 2 milligrams is absorbed. Although termed an "inhaler," studies have shown that the nicotine vapor is deposited mainly in the mouth, and hence absorption rates resemble that of nicotine gum. The inhaler can provide some of the behavioral and sensory characteristics associated with smoking and may therefore be appealing to smokers seeking a weaning tool that provides these components. However, the sensory effects of nicotine also can produce adverse effects, including mouth irritation and cough.

Commonalties across NRT products.

Each of the four NRT systems discussed has been shown to facilitate smoking cessation, approximately doubling or tripling abstinence rates over placebo. They are effective even in the absence of a formal behavior therapy program, although behavioral treatment in combination with the nicotine replacement further enhances success rates. Interestingly, success rates are similar across the different methods, although more research needs to be done to determine whether different types of smokers will benefit more from one treatment than another.

What is missing from nicotine replacement?

One might suppose that with the varied nicotine replacement techniques available, success rates in smoking cessation treatment would be higher than the typical long-term outcome (e.g., at one year) of 10 to 20 percent. Unfortunately, the vast majority of smokers relapse to cigarettes, raising the question of what is missing from NRT that cigarettes provide. It has been widely believed that the rapid absorption of nicotine from the lung during cigarette smoking accounted for the unique addictiveness of cigarettes; however, some doubt has been cast on this interpretation in view of the modest efficacy of the nasal spray despite extremely rapid absorption of nicotine, and by laboratory studies indicating that even rapid intravenous nicotine injections do not reproduce the enjoyable aspects of cigarette smoking. Research has suggested at least two other key components may be missing from NRT. One component alluded to above, consists of the sensory and behavioral cues associated with inhalation upon which smokers have become dependent. Although the nicotine inhaler provides some of these cues, it does not deliver tobacco taste or replace what smokers find to be enjoyable sensations of inhaling cigarette smoke. A second component that may also be important entails non nicotine constituents in tobacco that inhibit an enzyme (monoamine oxidase) important to the breakdown of neurotransmitters in the brain (e.g., dopamine), which in turn may mediate the chemical reward of nicotine. Methods of replacing these missing components are being developed and may yield further improvements in treatment efficacy.

Bupropion.

Bupropion was the first non nicotine pharmaceutical to be approved by the U.S. food and Drug Administration for smoking cessation treatment and had been marketed previously as an antidepressant. However, it is efficacious in smoking cessation treatment even for smokers who are not depressed. Although the mechanism of action relevant to smoking cessation has not been elucidated, bupropion raises the level of brain neurotransmitters involved in drug reward, such as dopamine and norepinephrine. Bupropion has also been shown to block the action of nicotine at certain receptors. Clinical trials have demonstrated that bupropion approximately doubles success rates over placebo, and the most frequent side effects include insomnia and dry mouth.

Combination approaches.

Many potential combination approaches have yet to be thoroughly evaluated; they may increase success rates beyond those of any one technique alone. This has already been seen in the enhancement of success rates with NRT by behavior therapy programs. Additional treatment combinations may include the use of two or more nicotine delivery systems at the same time. A patch might provide a steady baseline level of nicotine, which could be supplemented as the need arises by the use of gum, nasal spray, or the inhaler. Another promising combination may be NRT plus bupropion, which some research suggests may have additive benefits. Combinations of NRT and techniques that provide some of the missing components of tobacco discussed above may also be considered. These and other possibilities need to be tested in future research because smoking has proven to be a more formidable adversary, as well as a more tenacious addiction, than many would have initially suspected.

JED E. ROSE