Nicotine science

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 nicotine that is grounded in science. 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:

1. 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 this important societal question. More information can be found in our eighth Scientific Update, which is dedicated to a review of nicotine.
2. We understand the need for, and actively work toward, commercializing tobacco and other nicotine-containing products responsibly. We aim 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. You can read more about our sales and marketing practices on page 83 of the Integrated Report.
3. We conduct post-market studies to understand how our products are used and by whom. Such studies verify the results of our premarket perception and behavior assessments and monitor whether current adult smokers switch to the products, as well as whether never or former smokers use them. By conducting post-market studies, we are able to evaluate potential changes in prevalence; assess initiation, relapse, and complete-quit rates; and compare the use of cigarettes and smoke-free products.

The route of nicotine administration (e.g., via the lung, mouth, or skin) influences the speed and amount of nicotine uptake into the body. When tobacco smoke or e-cigarette aerosol is inhaled into the lung, it is rapidly absorbed into the bloodstream and can reach the brain as quickly as 10–20 seconds after the puff is taken. Nicotine from oral tobacco products (e.g., snus, nicotine pouches, NRT gum) is absorbed into the bloodstream through oral tissues, and the nicotine concentration in the blood rises gradually, reaching a plateau in about 30 minutes. The rise in brain nicotine concentration is slower compared with the inhalation route. A certain amount of the orally administered nicotine is swallowed and absorbed, mostly in the small intestine, before passing to the liver, where it is metabolized (i.e., transformed to facilitate excretion of nicotine from the body). Nicotine, when absorbed through the skin, reaches a plateau concentration in the blood more slowly than via other routes of administration. However, the level typically is maintained for a longer period.

Once nicotine is absorbed into the circulatory system, it is distributed to all body tissues and organs, including the brain. There, nicotine binds to specific receptor molecules, mimicking the actions of a naturally occurring brain chemical, the neurotransmitter acetylcholine. Nicotine is metabolized mainly in the liver. Nicotine absorbed via the lung and oral tissues reaches the brain directly without first passing through the liver to be metabolized, whereas nicotine absorbed via the gut passes first through the liver to be metabolized and is partially excreted before reaching the brain.

Continual use of nicotine may lead to dependence or physiological adaptations to maintain homeostasis, which are most evident in the emergence of withdrawal symptoms experienced during cessation. In addition to other physiological responses, long-term use of nicotine can induce changes in the brain’s reward and stress systems, which may manifest as anxiety, dysphoria, and other negative affect states during long-term withdrawal. Physiological dependence, coupled with altered responses from the reward and stress system, can make quitting very difficult.

The rapid uptake and delivery of nicotine to the brain’s reward system via lung delivery is thought to be a primary reason for the addictive potential of cigarettes and other inhaled tobacco products. 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 it is metabolized. 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.

Two critical factors are the dose and rate of nicotine delivery. NRTs and other cessation products can help address nicotine withdrawal symptoms. The use of NRTs is 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 of relapse. NRTs, however, are not as satisfying as cigarette smoking. Firstly, they do not provide the ritual, sensory experience, and social components that complete the experience of consuming nicotine via smoking. Secondly, the route and speed of absorption of nicotine is different: Often, the NRTs that rapidly deliver high doses of nicotine, such as sprays and inhalators, are more satisfying to smokers than are those that slowly deliver nicotine at much lower doses, such as gums and patches.

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 to 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 for IQOS to have a nicotine delivery 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 IQOS use and reached more than 88 percent of the level attained with cigarettes. It, therefore, has an addictive potential similar to cigarettes. But at the same time, IQOS has the potential to be a satisfying alternative to continued smoking, the most harmful form of nicotine consumption.

After reviewing the scientific package on IQOS, the U.S. Food & Drug Administration (FDA) concluded, “[Pharmacokinetic] studies show Marlboro, Smooth Menthol, and Fresh Menthol Heatsticks have nicotine delivery, addiction potential, and abuse liability similar to combusted cigarettes. This is potentially beneficial for smokers trying to switch to IQOS as they are more likely to have satisfactory results and not resume [combusted cigarette] smoking.”²

These include treatments for patients suffering from schizophrenia, depression, and anxiety disorders. Scientists are also studying the effects of nicotine on debilitating diseases and disorders such as Tourette’s, Alzheimer’s, Parkinson’s, attention deficit hyperactivity disorder (ADHD), and others.

We believe a greater societal focus on the health impact of nicotine in isolation is needed, and we plan to play our part in furthering this understanding through our research.