Up to the end of the 1970s behavioral treatments were the only procedures with some efficacy available. Particularly the aversive method "rapid smoking" had a reasonably good efficacy record.
Early Development of Nicotine Replacement Therapy
The first scientifically evaluated drug treatment for tobacco dependence or smoking cessation, nicotine replacement therapy (NRT), was conceptualized in 1967 and developed in Sweden during the 1970s. Two physicians at the University of Lund, Stefan Lichtneckert and Claes Lundgren, approached the nearby pharmaceutical company AB Leo with the idea of using nicotine for smoking cessation after they had observed crew members in a submarine use smokeless tobacco. The notion that tobacco use was driven by nicotine was not widespread in the late 1960s, and AB Leo's research director, Ove Fernö, himself a heavy smoker, agreed to fund Drs. Lichtneckert and Lundgren's research.
After trying several administration forms (including aerosol) the researchers chose gum, mainly for safety reasons. The first gum was abandoned because it released its nicotine too quickly. In order to slow down the release, Dr. Fernö introduced the use of an ion exchanger into which the nicotine could be incorporated, a complex binding the nicotine to the gum until it comes into contact with saliva when it is released. However, using the ion exchanger complex slowed down the release of nicotine; in order to improve absorption a buffer was added to the gum.
Around 1973 Professor Michael Russell at the Department of Psychiatry at Denmark Hill in London became interested in the idea of using nicotine in smoking cessation after having used behavioral methods without much success. In the United States, Murray Jarvik and Nina Schneider were the first researchers to experiment with nicotine gum and they became great ambassadors of the product. At the Medical School at the University of Lund, a Smoking Cessation Clinic established and headed by Professor Håkan Westling came to use gum liberally for its patients beginning in 1970. The experience from the uncontrolled clinical use by Drs. Lichtneckert and Lundgren was important for testing out various reformulations of the gum that were used later in the centers above.
Initial Marketing Authorizations
In Sweden there was a discussion about whether the food or the medicine agencies should regulate nicotine gum. Gum was considered food, but nicotine was not an approved food additive. After several years, during which the Swedish tobacco monopoly showed an intention to market the gum, the government decided that the gum should be regulated as a medicine.
Nicotine gum was first approved in Switzerland in 1978. In a U.S. regulatory agency advisory committee meeting in 1983, there was a lot of controversy surrounding the gum's possible approval. Fear of abuse of the gum was cited as one of the FDA's concerns.
Nicotine Nasal Spray
It was evident that a gum could not deliver nicotine with the same speed and to the same extent that a cigarette could. As a way to remedy the relatively slow absorption of nicotine from the gum, in 1979 Professor Russell and Dr. Fernö agreed to investigate the absorption of nicotine through the nose. Russell's group headed most of the clinical development with the nicotine nasal spray and advocated that in a smoker's clinic with heavy dependent smokers it was the most effective tool. In the United States in the 2000s, nicotine nasal spray and nicotine inhalers are available by prescription.
The Nicotine Patch
In the early 1990s it became clear that not every cigarette smoker could or liked to chew gum, and many experienced side effects like irritation in the oral cavity and some indigestion. This led to underdosing and thoughts on how to remedy the problem. In 1984, Drs. Jed Rose and Murray Jarvik from the University of California Los Angeles (UCLA) began to experiment with nicotine given transdermally (through the skin). They applied for a patent for transdermal delivery of nicotine, which was later approved. Around the same time, U.S.-based ALZA Corporation and the German-based Lohman Therapie Systeme started to develop nicotine patches, which are similar to adhesive bandages and are available in different shapes and sizes. The nicotine patch releases a constant amount of nicotine in the body; the nicotine dissolves through the skin and enters the body, thus providing relief from some of the withdrawal symptoms people experience when they quit smoking.
Other Nicotine-Delivery Products
In the 1990s and early 2000s, a number of nicotine-delivery products were developed by different pharmaceutical companies. In order to provide consumer options, Pfizer developed an oral inhaler. This preparation delivers nicotine with approximately the same characteristics as a 2-milligram gum and the efficacy is also the same. The Swiss company, Novartis, was the first to develop a lozenge with a 1-milligram dose, later followed by a 2-milligram dose. UK-based GlaxoSmithKline developed a 2- and 4-milligram lozenge that roughly mimics the pharmacokinetics of the Pfizer and Novartis 2- and 4-products.
Nicotine Replacement Therapy in the Future
Since the mid-1980s consumers have witnessed the medicine regulatory authorities outside the United States relaxing their attitude toward nicotine and the expressed safety concerns. Since this time, many contraindications have been lifted, better availability—from prescription-only, over the counter, and general sale—has been allowed, and wider use with new indications like temporary abstinence and reduced smoking has been granted. In the 2000s, patches are only used for complete cessation while the other products are used for both cessation and relapse prevention, reducing smoking, and recreational use. The gum formulation is the best-selling product both in the United States and worldwide, followed by the patch.
"It is argued that it is not so much the efficacy of new nicotine delivery systems as temporary aids to cessation, but their potential as long-term alternatives to tobacco, that makes the virtual elimination of tobacco a realistic future target," Michael Russell wrote in The Lancet (1991). How nicotine will be consumed in the future has to do with how it will be regulated. Public health officials have maintained that a regulatory framework—where one agency has the power to regulate all nicotine-containing products—would be instrumental in determining the best public health impact of cessation products and abstinence from nicotine. In the United Kingdom, organizations such as the British Royal College of Physicians and the House of Commons have petitioned the British Department of Health to move in that direction.
▌ KARL FAGERSTRÖM
Bolliger, Christoph T., and Karl-Olov Fagerström, eds. The Tobacco Epidemic. Vol. 28, Progress in Respiratory Research. New York: Karger, 1997.
Haustein, Knut-Olaf. Tobacco or Health? Physiological and Social Damages Caused by Tobacco Smoking. New York: Springer, 2003.
Schneider, N. How to Use Nicotine Gum. New York: Simon & Schuster, 1988.
ion exchanger complex a method of controlling the nicotine levels of cigarettes by adding ion exchangers, usually resins, to the tobacco or filter.
pharmacokinetics the branch of medicine that deals with the action of drugs within the body, specifically absorption, distribution, and elimination.