Nicotine

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Nicotine
It is widely accepted that most of the harm associated with tobacco is caused by inhaling the smoke produced by its combustion — not by nicotine.
 
What is nicotine?

Nicotine is a naturally occurring organic compound. Tobacco plants contain the highest levels of naturally occurring nicotine, but it can also be found at much lower levels in other natural sources, such as potatoes, tomatoes, and eggplants. Nicotine can also be produced in a laboratory, which is commonly known as synthetic nicotine.

It is a chiral molecule with two stereoisomers that have an asymmetrical form that cannot be superimposed on its mirror image, S-nicotine and R-nicotine. In tobacco, it is comprised almost entirely of S-nicotine (>99%), while synthetic nicotine is comprised of both S-nicotine and R-nicotine.i

Watch the video to learn more about nicotine:

What is nicotine
A scientific view on the nicotine molecule

Nicotine is the major alkaloid commercially derived from tobacco leaves and is the primary substance in tobacco responsible for the addictive properties of tobacco products.

Whilst generally considered addictive and not risk-free, it has been recognised by the World Health Organizationii  and other national health authoritiesiii  that nicotine itself does not directly cause cancer. The primary cause of smoking-related disease is exposure by inhalation to the many toxicants, as many as 7,000, created by the burning of tobacco.

Once nicotine has entered the bloodstream, it is distributed throughout the body to the tissue and organs, including the brain. Nicotine exerts its effects by binding to nicotinic acetylcholine receptor’s (nAChR’s), a family of ligand gated ion channels that are widely expressed and present throughout the body’s central and peripheral nervous system. Nicotine’s interaction with nAChRs in the brain causes the release of neurotransmitters, such as dopamine, GABA (Gamma-Aminobutyric Acid), glutamate and noradrenaline, which are responsible for the psychopharmacological effects of nicotine.

Nicotine is a 2-(3-pyridyl)-substituted analog of N-methylpyrrolidine and is related both structurally and biosynthetically to nornicotine, myosmine), (β-nicotyrine, N′-isopropylnornicotine, norcotinine) and cotinine.

Molecular structure of nicotine
The role of nicotine in Tobacco Harm Reduction

Given the extensive use of nicotine via tobacco products globally, with an estimated 1.3 billion smokers worldwideiv, there is already a wealth of evidence about nicotine’s effects when delivered by smoking a cigarette. However, there is a need to continue to generate additional data and scientific evidence about nicotine as a compound and its effects beyond those experienced by cigarette smokers.

With the increasing availability of various alternative tobacco and nicotine products, further research on nicotine is warranted. An array of scientific studies has contributed to the available evidence regarding nicotine’s effects, which helps to inform the important role it can play in Tobacco Harm Reduction (THR), a public health strategy to minimise the projected negative public health impact of smoking. Reduced Risk Products (RRPs)*†, such as vaping products, tobacco heating products and nicotine pouches, provide a source of nicotine for smokers seeking an alternative to continuing to smoke conventional cigarettes.

The science behind nicotine

Nicotine is an addictive compound. Smokers enjoy the pleasurable effects of nicotine and have cited those pleasurable effects as a reason for continued smoking. The broad range of nicotine’s effects when delivered by products other than cigarettes continues to be widely researched and resulting data may play an important role in ensuring the acceptability of RRPs as complete alternatives to combustible cigarettes, enabling individuals who would otherwise have continued to smoke, to switch to RRPs instead.

Physiological and psychological functions
Scientific evidence indicates that nicotine may influence numerous physiological and psychological functions, such as body weight, cognitive function, and emotion. Enjoyment of these functional effects has been cited by some as reason to continue to smoke or for resumption of smoking following a period of cessation.v,vi, For example, loss of nicotine’s perceived effect of increasing concentration has been reported as a factor leading to resumption of smoking.vii
Cognitive function
Various studies have demonstrated that nicotine can have a perceived beneficial effect on cognitive function in some older adults with memory, attention, and cognitive impairment. Nicotine has also been studied as a potential therapeutic agent for an array of conditions including ulcerative colitis, Alzheimer's diseaseviii, Parkinson's diseaseix, Schizophreniax and attention deficit hyperactivity disorderxi.
Weight management
Another area of investigational research relevant to reported reasons for continued smoking, is the effects of nicotine on body weight. The findings of a recent literature review of nicotine studies suggests that the decrease in body weight and food intake observed across the studies may be attributed to nicotinic alterations. The authors of the review concluded that the “evidence supports nicotine decreasing appetite and body weight, which may be due to a combination of nicotine targeting central neurons and increasing energy expenditure, though the effect on food intake remains unclear” and that “further research evaluating the effect of nicotine on appetite hormones, FI [food intake] and EE [energy expenditure] in humans is warranted.”xii
Scientific literature
Due to the various methods of nicotine delivery, and to close the gaps in the current scientific literature, new studies that assess the impact of nicotine on cognition, smoking urges and moodxiii as well as appetite and food intakexiv are being undertaken by BAT.
Other effects
Beyond these areas, it is important to consider a broad range of scientific research about nicotine and its effects. The effects of nicotine on the cardiovascular systemxv,xvi, the central nervous systemxvii,xviii, skinxix and inflammatory disordersxx have been widely discussed in the scientific literature.

Other studies have reported that foetal exposure to nicotine during pregnancy can result in adverse consequences, including adverse reproductive outcomesxxi. Some authorities assert that nicotine exposure during youth can lead to adverse neural and behavioural alterationsxxii. Oral ingestion or dermal absorption of e-cigarette liquids containing nicotine can result in nicotine poisoning depending on the dose and other circumstances, such as nicotine tolerance and body weight. Therefore, it is essential that adult consumers keep nicotine products out of the reach of children and should stop using any nicotine product immediately and seek medical advice if they experience any unusual or adverse effect.
New and emerging research: peer-reviewed publications

BAT invests significantly in building considerable scientific data to substantiate its alternative tobacco and nicotine products as reduced risk compared to cigarette smoking*†. Since 2018, we have invested over £1.2 billion in research and development activities. Our 1,500 R&D experts have published more than 150 peer-reviewed studies about these alternative products.

Alongside an extensive R&D programme for each of its alternative tobacco and nicotine products, BAT has also been conducting several exploratory studies into the various effects of nicotine itself.  Building on the existing data and the gaps identified in the existing knowledge, BAT has undertaken a number of studies and meta-analyses to provide additional evidence about nicotine, including reported effects described above.

Read some of the latest publications:

It is believed that the findings from these studies can help provide much needed new evidence and inform potential future research into encouraging individuals, who would otherwise have continued to smoke, to switch to RRPs. 

*Based on the weight-of-evidence and assuming a complete switch from cigarette smoking. These products are not risk free and are addictive.

† Our products as sold in the US, including Vuse, Velo, Grizzly, Kodiak, and Camel Snus, are subject to FDA regulation and no reduced-risk claims will be made as to these products without agency clearance.

This page is not intended as a piece of promotional material for any products, very notably in the US where claims of a certain type are subject to FDA clearance. This update relates to scientific data and is not aimed at a specific market. It is intended to provide further scientific evidence to underpin nicotine, as compound.

References
i Tobacco Control: Synthetic nicotine has arrived. (bmj.com). https://tobaccocontrol.bmj.com/content/early/2021/09/07/tobaccocontrol-2021-056626
ii WHO IARC European Code Against Cancer. Does nicotine cause cancer? Undated. Retrieved on 17 November 2021, from https://cancer-code-europe.iarc.fr/index.php/en/ecac-12-ways/tobacco/199-nicotine-cause-cancer : “Does nicotine cause cancer? No. Nicotine is a common chemical compound found in tobacco plants, and its effect is to make tobacco addictive rather than to cause cancer directly”.
iii The UK National Health Service states: “The evidence shows that while nicotine is the addictive substance in cigarettes, it is relatively harmless. In fact, almost all of the harm from smoking comes from the thousands of other chemicals in tobacco smoke, many of which are toxic.” https://www.gov.uk/government/publications/smoking-and-tobacco-applying-all-our-health/smoking-and-tobacco-applying-all-our-health
iv According to the World Health Organization (WHO), 1.3 billion men, women and children worldwide are smokers. https://www.who.int/news-room/fact-sheets/detail/tobacco
v Hughes J. Effects of abstinence from tobacco: Valid symptoms and time course. Nic Tob Res. 2007;9:315-27
vi Ashare et.al 2014. Cognitive function during nicotine withdrawal: Implications for nicotine dependence treatment. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779499/
vii Heishman SJ, Taylor RC, Henningfield JE. Nicotine and smoking: a review of effects on human performance. Exp Clin Psychopharmacol. 1994; 2:345–395
viii White HK, Levin ED. Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer's disease. Psychopharmacology (Berl). 1999 Apr; 143(2):158-65. doi: 10.1007/s002130050931. PMID: 10326778
ix Lieberman A, Lockhart TE, Olson MC, Smith Hussain VA, Frames CW, Sadreddin A, McCauley M, Ludington E. Nicotine Bitartrate Reduces Falls and Freezing of Gait in Parkinson Disease: A Reanalysis. Front Neurol. 2019 May 7;10: 424. doi: 10.3389/fneur.2019.00424. PMID: 31133957; PMCID: PMC6514133
x Dulude, Louise PhD*; Labelle, Alain MD†‡; Knott, Verner J. PhD, C Psych†‡. Acute Nicotine Alteration of Sensory Memory Impairment in Smokers With Schizophrenia. Journal of Clinical Psychopharmacology: October 2010 - Volume 30 - Issue 5 - p 541-548 doi: 10.1097/JCP.0b013e3181f0c9c6
xi Levin ED, Conners CK, Sparrow E, Hinton SC, Erhardt D, Meck WH, Rose JE, March J. Nicotine effects on adults with attention-deficit/hyperactivity disorder. Psychopharmacology (Berl). 1996 Jan;123(1):55-63. doi: 10.1007/BF02246281. PMID: 8741955.
xii Schwartz A, Bellissimo N. Nicotine and energy balance: A review examining the effect of nicotine on hormonal appetite regulation and energy expenditure. Appetite. 2021 Sep 1;164:105260. doi: 10.1016/j.appet.2021.105260. Epub 2021 Apr 20. PMID: 33848592.
xiii Green HJ, O’shea OK, Philpott HL, Newland N. An exploratory, randomised, crossover study to investigate the effect of nicotine on cognitive function in healthy adult smokers who use an electronic cigarette, after a period of smoking abstinence: study protocol. Int J Clin Trials 2022;9(2):136-42
xiv Olivia K. O’Shea, Harry J. Green, Helen L. Philpott, Nik Newland. An exploratory, randomised, crossover study to investigate the effect of a nicotine containing electronic cigarette on appetite in healthy adult smokers, after a period of smoking abstinence: study protocol. 2022. https://doi.org/10.18203/2349-3259.ijct20222692
xv Benowitz NL, Burbank AD. Cardiovascular toxicity of nicotine: Implications for electronic cigarette use. Trends Cardiovasc Med. 2016 Aug;26(6):515-23. doi: 10.1016/j.tcm.2016.03.001. Epub 2016 Mar 10. PMID: 27079891; PMCID: PMC4958544.
xvi Price LR, Martinez J. Cardiovascular, carcinogenic and reproductive effects of nicotine exposure: A narrative review of the scientific literature [version 2] F1000Research 2020, 8:1586, https://doi.org/10.12688/f1000research.20062.2 Ferrea S, Winterer G. Neuroprotective and neurotoxic effects of nicotine. Pharmacopsychiatry 2009; 42: 255 – 265. doi: 10.1055/s-0029-1224138.
xvii Ferrea S, Winterer G. Neuroprotective and neurotoxic effects of nicotine. Pharmacopsychiatry 2009; 42: 255 – 265. doi: 10.1055/s-0029-1224138.
xviii Archie SR, Sharma S, Burks E, Abbruscato T. Biological determinants impact the neurovascular toxicity of nicotine and tobacco smoke: A pharmacokinetic and pharmacodynamics perspective. NeuroToxicology 2022 89, pp. 140-160. https://doi.org/10.1016/j.neuro.2022.02.002.
xix Misery L. Nicotine effects on skin: are they positive or negative? Exp Dermatol. 2004 Nov;13(11):665-70. doi: 10.1111/j.0906-6705.2004.00274.x. PMID: 15500638.
xx Zhang W, Lin H, Zou M, Yuan Q, Huang Z, Pan X, Zhang W. Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects. Front. Immunol. 2022 13:826889. doi: 10.3389/fimmu.2022.826889
xxi Banderali, G., Martelli, A., Landi, M. et al. Short and long term health effects of parental tobacco smoking during pregnancy and lactation: a descriptive review. J Transl Med 13, 327 (2015). https://doi.org/10.1186/s12967-015-0690-y
xxii U.S. Department of Health and Human Services (USDHHS). E-Cigarette Use Among Youth and Young Adults: A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2016.
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