|INTEGRATED REPORT 2020|
To PMI, this topic is about better understanding nicotine and its role in addiction, separate from the risks to health associated with the use of our products, in particular those that combust tobacco.
The right thing to do
Nicotine is the most well-known molecule in tobacco. Because it is so well known and because smoking is the most common source of nicotine uptake, people tend to wrongly associate all the dangers of smoking with nicotine. While nicotine is addictive and not risk-free, it is not the primary cause of smoking-related diseases. These diseases are associated primarily with the exposure to toxic substances emitted in the smoke when the tobacco is burned, and not with the exposure to nicotine. In fact, nicotine is a key ingredient in nicotine replacement therapies designed to help smokers quit smoking.
At the same time, nicotine does cause addiction to tobacco and nicotine-containing products, which can make them hard to quit. It can also increase a person’s heart rate and blood pressure. Minors, pregnant women, or nursing mothers, and people with existing conditions such as heart disease, high blood pressure, diabetes, or epilepsy, should not use tobacco or nicotine-containing products.
Independent studies have shown the harm-reduction potential of making better alternatives than cigarettes available to adult smokers who would otherwise continue to smoke (read more on the “Product health impacts” page). If nicotine could be provided in a form that is acceptable and effective as a cigarette substitute, millions of lives could be saved. For that to happen, smokers who would otherwise continue to smoke, and do not quit, need access to less harmful alternatives to cigarettes. Among the leaders of change are public health organizations and regulatory bodies, whose opinions and decisions impact everyone involved. Many agree that tobacco harm reduction, as an addition to (and not a replacement of) existing tobacco control measures is the right route to take.
The Royal College of Physicians has said: “Nicotine is not, however, in itself a highly hazardous drug (…) it is inherently unlikely that nicotine inhalation itself contributes significantly to the mortality or morbidity caused by smoking. The main culprit is smoke and, if nicotine could be delivered effectively and acceptably to smokers without smoke, most if not all of the harm of smoking could probably be avoided.”
The business case
Nicotine plays a key role in the successful adoption of our smoke-free products—its presence can help adults who would otherwise continue smoking to switch to less risky alternatives instead. In addition to taste, ritual, and the sensory aspects, nicotine uptake that is comparable to cigarettes is important for adult smokers to accept novel alternatives to smoking. This is why we have researched and continue to develop a portfolio of smoke-free, nicotine-containing products that are a better choice for adult smokers than continuing to smoke cigarettes.
We understand the need for, and actively work toward, commercializing tobacco and other nicotine-containing products responsibly. Our aim is to guard against marketing and sales of our smoke-free products to nonsmokers and minimize access for underage purchasers. Our commercialization practices support this business vision: To make adult smokers aware that better alternatives to cigarettes exist and to move those who otherwise would not quit cigarettes to our smoke-free products. Doing this responsibly by directing our marketing and sales activities toward adult smokers, and providing them with accurate and relevant information about our products, is fundamental to our long-term success.
Achieving our aims
We are working hard to achieve a future without cigarettes. As society progresses toward the elimination of cigarettes, the most harmful form of nicotine delivery, there needs to also be education and a societal debate about what nicotine is and what it is not. The world will certainly be a better place without cigarettes, but it is difficult to envision how to achieve this in a timely manner without nicotine-containing alternatives that deliver an acceptable sensory experience.
In this domain, we are acting on three axes:
- We continue to analyze the risks and potential benefits of nicotine use, when not in combination with combusted tobacco, and share our findings to encourage a science-based debate on these important societal questions.
- We aim to commercialize our products responsibly, helping to guard against use by unintended audiences such as never and former smokers, and youth.
- We conduct post-market studies to understand how our products are used and by whom. Such studies verify the results of the premarket perception and behavior assessments and monitor whether current adult smokers switch to the products, as well as whether never and former smokers use them. By conducting post-market studies, we are able to evaluate potential changes in prevalence; to assess initiation, relapse, and complete-quit rates; and to compare the use of cigarettes and smoke-free products. When appropriate, results of our post-market monitoring are shared with regulators. More information can be found in our eighth Scientific Update, which was dedicated to a review of nicotine and is available on our PMIScience website.
What is nicotine?
Nicotine occurs naturally in tobacco and, at significantly lower levels, in some other plant varieties from the Solanaceae family, which includes tomatoes, potatoes, and eggplant. It is possible to extract nicotine from tobacco, as is done to produce the nicotine contained in nicotine replacement therapy products and e-liquids for e-cigarettes. It is also possible to produce synthetic nicotine. While this process is relatively costly, there are an increasing number of products (e-liquids) that are now using synthetic nicotine.
Since prehistoric times, people have recognized the stimulating effects of burning dried tobacco leaves. Throughout history, smoking tobacco has been the most common form of nicotine uptake. A single cigarette contains approximately 12 milligrams (mg) of nicotine, but only a fraction (<2 mg) of that nicotine is transferred into the smoke inhaled by the cigarette smoker.
The route of uptake (through the lungs, mouth, or skin) determines the speed and intensity of nicotine delivery. When tobacco smoke is inhaled via cigarettes, nicotine is absorbed through the lungs into the bloodstream and reaches the brain in about 10 to 20 seconds. Through other routes, such as absorption through the skin when using a nicotine patch or through the mouth and stomach when chewing nicotine gum, nicotine is absorbed more slowly, at lower peak exposure, and therefore takes longer to reach the brain.
Once absorbed, nicotine enters the bloodstream and is distributed to all tissues and organs, including the brain. There, nicotine binds to specific receptor molecules, mimicking the actions of a naturally occurring brain chemical, acetylcholine. Nicotine is metabolized, mainly by the liver, and is constantly cleared from the body.
Nicotine and addiction
Nicotine is an addictive chemical compound present in tobacco and tobacco products. But the addictive properties of smoking are a more complex interaction of factors beyond nicotine alone—the ritual, sensory experience, and social experiences all play a significant role in addiction. Exposure to nicotine and the extent of its effects can also be influenced by individual differences in smoking behavior, metabolism, body mass index, and genetic differences.
Once nicotine enters the brain, it modulates the reward systems and, once nicotine leaves the body, it can lead to withdrawal symptoms, for example when someone tries to quit. Withdrawal symptoms—which can include difficulty concentrating, anxiety, and dysphoria (commonly understood as distress or discomfort with life)—affect many people when they initially quit smoking. The modulation of the reward system and withdrawal symptoms can make it very difficult to quit.
Many people assign most of the addictive power of cigarettes to how rapidly it is absorbed through the lungs and how quickly it moves from the lungs to the brain. When someone smokes a cigarette, the nicotine levels peak quickly (in about six to 10 minutes) and then the level of nicotine drops fairly rapidly, as the body naturally clears the nicotine from its system. Most nicotine replacement therapies do not provide this same pharmacokinetic profile, making them less likely to be addictive, but also less likely to satisfy smokers’ desire for nicotine.
One critical factor is the dose and rate of nicotine delivery. Nicotine replacement therapies (NRTs) and other cessation products can help address nicotine withdrawal symptoms. Most smoking cessation medications are recommended for eight to 12 weeks, although use for six months or longer may be necessary to achieve optimal quit rates. It makes sense to use NRTs to support smoking cessation for as long as the individual feels at risk from relapse. NRTs however, are not as satisfying as cigarette smoking because of the route and speed of absorption of nicotine; often the products that rapidly deliver high doses of nicotine, such as sprays and inhalers, are more satisfying to smokers as alternatives than those that slowly deliver nicotine at much lower doses, such as gums and patches.
Nicotine in our heat-not-burn product
Nicotine delivery from smoke-free products can resemble that of a cigarette, thus these devices tend to be much more satisfying for those switching to a less harmful substitute for cigarette smoking. Our IQOS heat-not-burn product is a smoke-free alternative for adult smokers who would otherwise continue smoking and is not a smoking-cessation product.
Nicotine plays an important role in encouraging adult smokers to switch from cigarettes to better alternatives such as IQOS. Therefore, it is important that IQOS has a nicotine profile similar to that of a cigarette. In two studies conducted in Japan, the peak concentration of nicotine in the blood occurred about six minutes after starting product use and reached more than 88 percent of the level reached with cigarettes. It therefore has an addictive potential similar to cigarettes. On the other hand, IQOS therefore also has the potential to be a satisfying alternative to continued smoking.
After reviewing the scientific package on IQOS, the FDA concluded “PK studies show Marlboro, Smooth Menthol, and Fresh Menthol Heatsticks have nicotine delivery, addiction potential, and abuse liability similar to CC. This is potentially beneficial for smokers trying to switch to IQOS as they are more likely to have satisfactory results and not resume CC smoking.”1
1The FDA does not endorse or approve tobacco products.
Therapeutic delivery of nicotine—other applications
The public health and scientific community continues to explore ways in which nicotine, when isolated and used as a potential therapeutic compound, could confer certain health benefits, for example in patients who suffer from schizophrenia, depression, and anxiety disorders. Scientists are also studying the effects of nicotine on debilitating diseases like Alzheimer’s, Parkinson’s disease, attention deficit hyperactivity disorder (ADHD), and others.