Big Question 6 - What is Nicotine?

What Are the Effects of Nicotine?

Adult nicotine consumers have reported a variety of desired and rewarding effects, such as relaxation, increased alertness, and cognitive improvements, including enhanced sustained attention abilities^[7]. However, there are also known acute adverse effects caused by nicotine^[8].

The effects of nicotine on a person depend on factors such as whether they are a regular nicotine consumer, as well as their body weight, age, and health status. The immediate (acute) cardiovascular effects of nicotine include temporary increases in heart rate and blood pressure, as well as constriction of blood vessels.

While these acute effects are transitory and do not pose health hazards by themselves for the vast majority of regular nicotine users, such physiological responses can lead to adverse effects in adult consumers with certain underlying health conditions. This is particularly so in people with pre-existing cardiovascular disease and diabetes.

Nicotine overdoses in recreational users are inherently self-limiting, as initial symptoms such as dizziness and nausea typically cause immediate cessation of use and the prompt resolution of such symptoms.

Does Nicotine Cause Cancer?

A common misconception is that nicotine, as a substance, is the cause of smoking-related diseases (such as lung cancer). The primary cause of smoking-related disease is not exposure to nicotine, but to the 150 toxicants among the over 7,500 distinct compounds created by the burning of tobacco^{[9],[10],[11]}. This lack of understanding is not surprising.

The World Health Organization (WHO) does not classify nicotine as carcinogenic^[12] and many other national health authorities recognise that nicotine, while addictive, does not directly cause cancer.

What Are the Long-Term Health Effects of Nicotine Use?

Nicotine, when removed from cigarette smoking, is not a driver of smoking-related disease. Kim et al. concluded in a 2021 systematic review that there were no significant differences between nicotine and non-nicotine groups for the risk of arrhythmia, non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death^[13].

Do Nicotine Effects Vary by Product Format or Category?

No, the effect of nicotine is not different with different products. However, there are differences in the rate at which nicotine is absorbed into the body with different products.

For adult cigarette smokers, nicotine is absorbed into the body relatively quickly via inhalation and this can be measured using clinical pharmacokinetic (PK) studies.

To facilitate adult smokers switching to lower risk^*† profile products, a similar delivery profile of nicotine can be useful for consumer acceptability. Studies have shown that other inhalation products (Heated Products and Vapour Products) can match the nicotine delivery of cigarettes, which is one of the reasons that tens of millions of adult smokers have switched to these types of products.

Oral Tobacco Products and Oral Nicotine Pouches have a different nicotine delivery profile. When using such products, the nicotine is delivered through the buccal mucosa (cheek walls, gums) and into the bloodstream, typically over a much slower, but often more prolonged, timeframe.

Clear Guidance on Who Should Not Use Nicotine

Nicotine is addictive and for adults only. The safest option is not to use tobacco products or nicotine. For those adult smokers, who would otherwise continue to smoke, they should switch completely to a lower risk^*† profile Smokeless Product.

Our Responsible Marketing Principles^[16] and Code^[17] are very clear and aligned with regulators and public health bodies that nicotine should not be used by the underaged and is not appropriate for use by pregnant or lactating women nor people with known health contraindications (Figure 1).

What is Synthetic Nicotine (and is it Different to Tobacco-Derived Nicotine)?

Nicotine used in Smokeless Products originates from two broad sources: nicotine extracted from the tobacco plant and synthetic nicotine, which is manufactured. To date, the predominant source has largely been from nicotine extracted from tobacco.

However, advances in chemical synthesis have enabled the commercial availability of synthetic nicotine, which is structurally identical to nicotine extracted from tobacco leaf.

As with all chiral compounds, nicotine exists as a racemic mixture of two forms – or enantiomers – that predict its biological activity. Tobacco-derived nicotine exists predominantly in the S-nicotine form (99%), with less than 1% in the R-nicotine form^[18]. Earlier synthetic nicotine products commonly contained a racemic 50:50 S/R mixture, which differs substantially from the predominately S‑nicotine profile found in tobacco^[19]. As S-nicotine is biologically active while R-nicotine is largely inactive^[20], further refinement of synthetic nicotine to match the ratio of S- and R- forms was required to ensure the same magnitude of physiological effect seen from the tobacco-derived counterpart. Modern manufacturing technologies now support the production of near‑100% S‑nicotine, closely aligning its chiral composition (and hence physiological effect) with that of tobacco‑derived nicotine.

Nicotine: The Future

Nicotine is integral to Tobacco Harm Reduction (THR). For adult smokers who would otherwise continue to smoke, having a choice of lower risk^*† profile tobacco and nicotine products to completely switch to is important.

Think of it this way: while nicotine is addictive, with smoking, it is the carrier (smoke) that leads to the primary causes of smoking-related diseases, not the active molecule (nicotine). This is the opposite of, for example, alcohol, which has an inert carrier (typically water) while the active alcohol (ethanol) has been defined as a Group 1 carcinogen^[21].

This ‘carrier versus active’ distinction is important when it comes to educating people about the true risk profile of nicotine and the causes of smoking-related disease. It is also fundamental when it comes to research around THR and the creation of lower risk^*† profile products that can deliver nicotine in a relatively inert carrier with a lower risk^*† profile compared to a cigarette smoke carrier.