What is nicotine?
Nicotine occurs naturally in tobacco and, in some plants from the Solanaceae family, at much lower levels. It is possible to extract nicotine from tobacco for use in nicotine replacement therapy (NRT) products, the liquids used for e-cigarettes, and other nontobacco nicotine products. It is also possible to produce synthetic nicotine. While this process is relatively costly, an increasing number of products on the market (e-liquids and nicotine pouches) contain synthetic nicotine.Nicotine binds to the nicotinic acetylcholine receptor to elicit a variety of physiological responses (e.g., a transient increased heart rate and blood pressure). These effects can be influenced by the route of administration (e.g., via lungs, mouth, or skin) that affects the rate and amount of nicotine uptake into the body.
Nicotine is addictive and not risk-free, but it is not the primary cause of smoking related diseases.
Learn more about nicotine on PMIscience.com.
Nicotine is present in many products including combustible tobacco products (e.g., cigarettes and cigars) and smoke-free products that provide nicotine without combustion (e.g., snus, nicotine pouches, e-cigarettes, and heated tobacco products).
Since smoking has been the most prevalent form of nicotine uptake for millennia, nicotine, smoking and tobacco use can be difficult to separate in people’s minds. However, the effects from exposure to nicotine-containing products, which can vary by delivery method and the substrate used, are distinct and separate from the effects of nicotine itself. External independent surveys reveal common misperceptions about the effects of nicotine among people who smoke and healthcare professionals.
National Data from the United States show that nicotine misperceptions are common among U.S. adults who smoke and, similarly, data from the Office for Health Improvement and Disparities in the UK have also demonstrated that a large portion of the population incorrectly believe that nicotine itself causes smoking-related cancers.1 Nicotine misperceptions also exist among healthcare professionals, where many wrongly believe that nicotine itself causes smoking-related diseases.2,3
Although cancer is a complex and multifactorial process and there is ongoing research into the relationship between nicotine and cancer development, what is known is that nicotine is not classified as a carcinogen by numerous public health bodies including the International Agency for Research on Cancer and the US FDA.4, 5
Nicotine is addictive and not risk-free, but it is the chronic exposure to the products of combustion that are generated at high levels when a cigarette is lit which is the primary cause of smoking-related diseases such as cancer, respiratory illnesses, and cardiovascular diseases.
The unfortunate outcome of these misperceptions for adults who smoke is that they tend to perceive nicotine to be as harmful to health as cigarette smoking and therefore may be dissuaded from switching to nicotine-containing products that do not require combustion.6
Furthermore, the misperceptions in healthcare professionals around the health effects of nicotine may discourage them from improving their knowledge or being able to differentiate the health effects of smoking from nicotine itself.
1“Four in 10 smokers incorrectly think nicotine causes cancer.” Press Release, Public Health England, March 14, 2018.
2 Steinberg MB, Bover Manderski MT, Wackowski OA, Singh B, Strasser AA, Delnevo CD. Nicotine Risk Misperception Among US Physicians. doi: 10.1007/s11606-020-06172-8. September 1, 2020.
3 Bover Manderski MT, Steinberg MB, Wackowski OA, Singh B, Young WJ, Delnevo CD. Persistent Misperceptions about Nicotine among US Physicians: Results from a Randomized Survey Experiment - PubMed (nih.gov), DOI: 10.3390/ijerph18147713, 2021.
4 https://www.govinfo.gov/content/pkg/FR-2012-04-03/pdf/2012-7727.pdf
5 https://monographs.iarc.who.int/list-of-classifications
6Snell LM, Colby SM, DeAtley T, Cassidy R, and Tidey JW. Associations Between Nicotine Knowledge and Smoking Cessation Behaviors Among US Adults Who Smoke. doi: 10.1093/ntr/ntab246 2022.
Importance and risks of nicotine
The presence of nicotine in smoke-free products is an important factor among others, including ritual, sensory and taste, to successfully move adults away from cigarettes through the adoption of smoke-free products.7
Many people who smoke cigarettes indicate that they do so for the perceived benefits, which include enjoyment, stress management, and relaxation. Additionally, some studies report that nicotine can enhance cognitive processes like improving attention, memory, and fine motor function.
As an agonist of nicotinic acetylcholine receptors, nicotine elicits a variety of transient cardiovascular effects such as increased heart rate and blood pressure.
Sustained nicotine use can induce changes in the brain’s reward and stress systems, leading to withdrawal symptoms, although the effects are transitory and reversible once people quit and successfully abstain from using tobacco and nicotine products.
It is well understood that nicotine is addictive and not risk-free. However, while it can be difficult for some, anyone can quit tobacco and nicotine altogether with sufficient motivation.
Some studies have found that nicotine may have adverse effects on fetal development such as low birth weight.
For all these reasons, some populations should avoid nicotine-containing products, such as minors, and women who are pregnant or breastfeeding, as well as people with pre-existing conditions including heart disease, high blood pressure, diabetes, or epilepsy.
Achieving the goal of phasing out cigarettes will require a debate informed by facts and science on the health effects of smoke-free products and nicotine itself. As of today, much of our understanding of the importance and risks of nicotine is confounded with smoking. Therefore, as more and more new products emerge that separate nicotine from some or all of the aspects of the smoking ritual, much more research is needed to fully understand these new products as well as the role of nicotine itself.
Nicotine and smoke-free products
It is important to remember that for smoke-free products to benefit public health, existing adult smokers have to be willing to switch to them. Nicotine is one of several product characteristics, along with taste, sensory experience, nicotine-delivery profile, and ritual characteristics, that adult smokers are looking for in alternative products.
Independent studies demonstrate the importance of making scientifically substantiated smoke-free products accessible to those adults who would otherwise continue to smoke (read more here).1,2 This means offering a range of noncombusted nicotine-containing products with substantially lower levels of harmful and potentially harmful constituents (HPHCs) than cigarettes, that are acceptable to adults who would otherwise continue to smoke, so they abandon cigarettes completely.
Public health institutions, individuals and organizations have also noted the important role nicotine can play in helping adult smokers transition away from cigarettes.
For example, the U.K.’s Royal College of Physicians stated that nicotine is not “in itself a highly hazardous drug,” and, “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.”3
1Aryal UR and Bhatta DN. Perceived benefits and health risks of cigarette smoking among young adults: insights from a cross-sectional study. Tobacco Induced Diseases volume 13, Article number: 22 (2015) DOI 10.1186/s12971-015-0044-9).
2Valentine G, Sofuoglu M. Cognitive Effects of Nicotine: Recent Progress. Curr Neuropharmacol. 2018;16(4):403-414.
3 https://www.rcplondon.ac.uk/file/3563/download
Learn more about nicotine on PMIscience.com.
Therapeutic delivery of nicotine
The scientific community continues to explore ways in which nicotine and other alkaloids present in the tobacco plant can be isolated and potentially used as therapeutic compounds.1 For instance, scientists are studying nicotine as a possible active ingredient in pharmaceutical applications for treating schizophrenia, depression, and other anxiety disorders.2 Scientists are also examining the potential effects of nicotine on treating conditions such as Tourette’s, Alzheimer’s, Parkinson’s, attention deficit hyperactivity disorder (ADHD), and other diseases.3 Cellular, animal, and human studies yielded some promising results, yet existing data are still not conclusive, and nicotine’s addictiveness could be a limiting adverse effect for its development as a therapeutic compound for human use. 4 In 2015, the U.S. National Institutes of Health funded a multi-center study designed to explore whether nicotine patches (used traditionally as NRT, to aid cessation) improve memory and functioning in patients with mild cognitive impairment, compared to placebo in 380 subjects exposed for two years.5
2 Smith RC, Warner-Cohen J, Matute M, et al. Effects of nicotine hnasal spray on cognitive function in schizophrenia. Neuropsychopharmacology 2006: 31:637-43.
Barr RS, Culhave MA, Jubelt LE, et al. The effects of transdermal nicotine on cognition in nonsmokers with schizophrenia and nonpsychiatric controls. Neuropsychopharmacology 2008: 33:480-90.
Featherstone RE, Siegel SJ. The Role of Nicotine in Schizophrenia. Int Rev Neurobiol. 2015;124:23-78. doi: 10.1016/bs.irn.2015.07.002.
3 Terry AV Jr, Jones K, Bertrand D. Nicotinic acetylcholine receptors in neurological and psychiatric diseases. Pharmacol Res. 2023 May;191:106764. doi: 10.1016/j.phrs.2023.106764. Epub 2023 Apr 10. PMID: 37044234.
4 Newhouse PA, Sunderland T, Tariot PN, Blumhardt CL, Weingartner H, Mellow A, Murphy DL. Intravenous nicotine in Alzheimer's disease: a pilot study. Psychopharmacology (Berl). 1988;95(2):171-5. doi: 10.1007/BF00174504.
Jones G, Sahakian B, Levy R, Warburton DM, Gray J. Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimer’s disease. Psychopharmacology 1992: 108: 485-94.
Wilson AL, Langley LK, Monley J, Bauer T, Rottunda S, McFalls E, Kovera C, McCarten JR. Nicotine patches in Alzheimer's disease: pilot study on learning, memory, and safety. Pharmacol Biochem Behav. 1995 Jun-Jul;51(2-3):509-14. doi: 10.1016/0091-3057(95)00043-v.
White HK, Levin ED.Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer’s disease. Psychopharmacology 1999: 143: 158-65.
5 https://mindstudy.org
Future of nicotine
A better understanding of the health impacts of nicotine separate from the method of delivery is needed. We know a lot about nicotine, but much of it is confounded with the effects of tobacco smoke. People have a lot of questions about nicotine, including its long-term effects, separate from the effects of smoking and the addiction potential of different types of products.
Steps should be taken by academic and industrial institutions alike to fully understand the short and long-term impacts of nicotine use. We plan to contribute to this understanding by conducting and publishing dedicated research focusing on understanding the effects of nicotine. We will communicate more about this in our next report.
