Forster Family Professor in Cancer Prevention
Professor
Department of Psychiatry
Director
Transdisciplinary Tobacco Use Research Center
University of Minnesota
Minneapolis, MN
"Quitting smoking is easy. I've done it a thousand times."
---Mark Twain
Unfortunately, for many people Mark Twain's quip about quitting smoking is a frustrating reality. Nicotine, a naturally found drug in tobacco, is the culprit. The person becomes physically and psychologically dependent on this substance, which can be as addictive as cocaine or heroin when inhaled, making it very difficult to give up smoking.
Just about half of all smokers who don't quit will die from a smoking-related illness, such as cancer or cardiovascular disease. Lung cancer, one of the most common smoking-related malignancies, remains the leading cause of cancer-related death in the US, a total greater than for the other five leading cancers combined. Tobacco use causes not only lung cancer, however. It is a risk factor for other types of malignancies as well, including stomach, cervix, kidney, esophagus, oral, bladder, throat, pancreatic cancers, and some types of leukemia. And despite the fact that the numbers of smokers in the US are declining, approximately 45 million Americans continue to smoke.
Although efforts to increase the success of smoking cessation initiatives continue, it remains difficult for many individuals to relinquish their dependence on nicotine products. With this in mind, researchers are turning to novel approaches to aid smokers in their attempts to quit. One intriguing avenue of exploration is the development of a nicotine vaccine.
Nicotine immunization is a novel treatment that targets the drug rather than the brain. The nicotine vaccine stimulates the immune system to develop antibodies that bind with the nicotine molecule, forming a complex that is too large to pass through the blood-brain barrier. This process potentially reduces the pleasurable effects from smoking and reduces the addiction to nicotine. The vaccine under study has few side effects on the central nervous system because the antibody itself is targeted specifically for nicotine and does not alter any functions of the brain. Animal studies have shown that the vaccine works by reducing and slowing the amount of nicotine that enters the brain, thereby reducing nicotine's addictive effect.
In recent years, preliminary human studies have been conducted to determine the safety of the nicotine vaccine, the necessary vaccine dose to yield sufficient levels of antibodies that target the nicotine molecule, and the scheduling of doses to yield maximum boost in antibody levels. A recent multisite (University of Minnesota, University of Nebraska, and University of Wisconsin) clinical trial randomly assigned smokers who were not necessarily interested in quitting to receive one of three doses of the vaccine or a placebo as well as "booster shots" one, two, and six months later. The participants, who noted they were not interested in quitting smoking, were followed for 38 weeks. Researchers found that the vaccine was well tolerated. Participants reported some aches and tenderness at the injection site, as well as headaches, muscle pain, or malaise. Most of these symptoms, which occurred at a similar rate in the placebo group, were mild and resolved within a few days. None required medical intervention. There also was no evidence of nicotine withdrawal symptoms after vaccine injection or evidence that smokers increased smoking intensity (by smoking more cigarettes or puffing harder) to compensate for the lower levels of nicotine delivered to the brain.
An intriguing finding was that, although this study was not designed to test the treatment effect, 38% of the participants in the high-dose vaccine group were able to quit smoking for at least 30 days. This was an impressive and completely unexpected finding because helping smokers to quit was not an aim of this study. In fact, in order to participate, smokers had to attest that they did not have a planned quit date for the next 30 days.
Two additional phase I/II clinical studies have been conducted that showed similar safety profiles and high abstinence rates in the highest nicotine dose or antibody level groups. Because the vaccine targets nicotine itself and doesn't affect brain function, there are fewer side effects, and because of the way it is delivered, compliance may be better than for current medications for quitting smoking. Rather than daily medication, a periodic booster would be all that is necessary to help smokers quit their nicotine addiction. It is thought that the vaccine is successful because of the reduced amount of nicotine entering the brain as well as its slow delivery to the brain. Vaccinated smokers don't experience the sudden "rush" of nicotine associated with pleasurable effects. Although not a miracle drug, it does have the potential to help decrease some smokers' dependence on nicotine. If successful, a vaccine would be just one tool among many available to smokers who wish to quit. Smoking is more than a response to nicotine--there are also behavioral components, and there must be behavioral components to any treatment.
In summary, the nicotine vaccine appears to be a promising intervention for tobacco dependence, as a quit smoking aid and complement to other treatment or as a relapse prevention aid. More research is required because other questions about the vaccine need to be answered, such as whether higher antibody levels can be sustained for longer periods, how long the effectiveness of the vaccine will last for a smoker, and whether the vaccine can be used to successfully prevent people who quit smoking from relapsing and starting to smoke again.
