Nicotine replacement therapy

Nicotine replacement therapy (NRT) is a medically approved way to treat people with tobacco use disorder by taking nicotine through means other than tobacco. It is used to help with quitting smoking or stopping chewing tobacco. It increases the chance of quitting tobacco smoking by about 55%. Often it is used along with other behavioral techniques. The use of multiple types of NRT at a time may increase effectiveness.

Common side effects depend on the formulation of nicotine. Nicotine replacement therapy works by reducing cravings caused by nicotine addiction.

They were first approved for use in 1984, in the United States. They are available as generic medications. All forms of nicotine replacement therapy have similar success rates in terms of helping people stop smoking. However, the likelihood that someone will stick to a certain treatment varies, with compliance being the highest with nicotine patches, followed by nicotine gum, inhalers, and nasal sprays. Using a few different nicotine replacement methods in combination may improve success rates in stopping tobacco use. Additionally, using nicotine replacement with counseling has been proven to improve tobacco abstinence rates. People who are severely dependent include those who smoke: more than one pack per day, within five minutes of awakening, while ill, when they wake up in the middle of the night, to ease withdrawal signs and symptoms.

Effectiveness

Evaluation of NRT in real-world studies produces more modest outcomes than efficacy studies conducted by industry-funded trials. The National Health Service (NHS) in England has a smoking cessation service based on pharmacotherapy in combination with counseling support. An Action on Smoking and Health (UK) (ASH) report claims that the average cost per life-year gained for every smoker successfully treated by these services is less than £1,000 (below the NICE guidelines of £20,000 per QALY (quality-adjusted life year). However, the investment in NHS stop smoking services is relatively low. A comparison with treatment costs for illicit drug users shows that £585 million is committed for 350,000 problem drug users compared to £56 million for 9 million users of tobacco. This is £6.20 for each smoker, compared to £1,670 per illegal drug user.

The claims for high efficacy and cost-effectiveness of NRT have not been substantiated in real-world effectiveness studies. Pierce and Gilpin (2002) stated their conclusion as follows: "Since becoming available over the counter, NRT appears no longer effective in increasing long-term successful cessation" (p. 1260). Quit rates showed a dramatic decrease between 4-weeks and one year. A quit rate of 53% at four weeks fell to only 15% at one year. Younger smokers, females, pregnant smokers and more deprived smokers had lower quit rates than other groups.

The efficacy for each of the formulations alone (lozenges, nasal spray, gum, and transdermal patch) to aid in smoking cessation is equal. Efficacy increases 15% to 36% with combining treatments such as gum and lozenges. Higher doses increase the chance of stopping smoking for a period of six months and more. For patches, the most efficient doses were 25 mg worn over 16 hours or 21 mg worn over 24 hours. The evidence suggests that 4 mg nicotine gum leads to higher quit rates compared with 2 mg in heavy smokers. Prescription nicotine replacement therapy is associated with higher odds of quit success, whereas over-the-counter NRT was not associated with higher quit success.

Toxicity

N-Nitrosonornicotine, a strong carcinogen present in unburned tobacco and cigarette smoke, has been found in the urine of some users of oral NRT products. Nicotine patches is an alternative.

Side effects

thumb|upright=1.6|Possible [[side effects of nicotine]]

Some side effects are caused by the nicotine, and are common to NRT products. Other common side effects depend on the formulation of nicotine. Although overdose is rare, it can be problematic, especially in children and pets. The symptoms of nicotine overdose include headache, pale skin and mouth, belly pain, weakness, diarrhea, tremors or seizures, agitation, confusion, restlessness, high or low blood pressure, fast or irregular heartbeat, fast breathing, and cold sweats.

A 2025 cardiovascular review described NRT as a time-limited cessation aid, rather than one for chronic use.

Safety

Pregnancy

Nicotine is not safe to use in any amount during pregnancy. Nicotine crosses the placenta and is found in the breast milk of mothers who smoke as well as mothers who inhale passive smoke. There are possible harms to the baby if NRT is used during pregnancy. There is evidence that nicotine negatively affects fetal brain development and pregnancy outcomes. There is also risk of stillbirth and pre-term birth. Nicotine use will probably harm fetal neurological development. Risks to the child later in life from nicotine exposure during pregnancy include type 2 diabetes, obesity, hypertension, neurobehavioral defects, respiratory dysfunction, and infertility. Evidence is unclear whether adolescents gain benefit from cognitive-behavioral therapy or smoking cessation over the long-term as of 2017. Most tobacco users are under-eighteens when they start, and almost no-one over the age of 25 starts using. In 2025, the efficacy of NRT in adolescents was still unclear.

Cardiovascular conditions

While there is no evidence that NRT can increase the risk of heart attacks,

Other conditions

Nicotine replacement therapies should be used cautiously in individuals with the following conditions: severe reactive airway diseases (for nasal spray), chronic nasal disorders such as sinusitis, polyps, rhinitis, or allergy (for nasal spray), diabetes (insulin-dependent), gastrointestinal diseases such as esophagitis, active gastric or peptic ulcer disease, liver problems, hyperthyroidism, pheochromocytoma, phenylketonuria (for lozenges), renal problems, and skin conditions such as psoriasis or dermatitis (for the transdermal patch).

Mechanism of action

Nicotine replacement therapy works by reducing cravings due to nicotine addiction. Nicotine from NRT does not reach as high a concentration in the blood as does nicotine from smoke inhalation due to different absorption methods. NRT relies on systemic venous absorption, whereas nicotine from cigarettes reaches the arterial system. It is possible to become dependent on some NRTs.

Nicotine patches are applied to the skin and continuously administer a stable dose of nicotine slowly over 16–24 hours. Nicotine gum, nicotine sprays, nicotine toothpicks, nicotine sublingual tablets, and nicotine lozenges administer nicotine orally with quicker nicotine uptake into the body but lasting a shorter amount of time. Nicotine inhalers are metered-dose inhalers that administer nicotine through the lungs and mucous membranes of the throat quickly, lasting for a short amount of time. For example, blood nicotine levels are the highest 5–10 minutes after using the nicotine nasal spray, 20 minutes after using a nicotine inhaler or chewing nicotine gum, and 2–4 hours after using a nicotine patch.

Society and culture

NRT products were first approved for use in the United States in 1984. Nicotine replacement products are available as generic medication.

|Patch

|Pouch

|Over-the-counter

|16 or 24 hours sustained-release transdermal patch

|Lozenge

|Blister pack

|Over-the-counter

|20 to 30 minutes modified-release dosage tablet containing nicotine polacrilex

|Sublingual tablets

|Blister pack

|Over-the-counter

|Quickly dissolves to releases nicotine through a hard candy

|Gum

|Blister pack

|Over-the-counter

|Chewing the gum releases nicotine as a modified-release dosage

|Mouth spray

|Mouth spray bottle

|Over-the-counter

|Spraying a mist into the mouth administers nicotine for buccal administration

|Vapour inhalator

|Nicorette Inhalator: with 10 mg nicotine disposable cartridges

|Over-the-counter

|Resembles cigarettes; A disposable cartridge contains about 10 mg nicotine (about 40% is released). Multiple inhaling through the mouthpiece administers sufficient nicotine.

|Pressurized Metered-dose inhaler (pMDI)

|Prescription

|Inhaling through the mouthpiece administers nicotine

|Nasal spray

|Nasal spray bottle

|Prescription

|Spraying a pump bottle into the nose administers nicotine

|Toothpicks

|Over-the-counter

thumb|209x209px|A can of [[Nic Nac Naturals lozenges ]]

The nicotine patch is a once-daily, longer-acting form of NRT. An advantage of the nicotine patch is its simple compliance; it does not require active use throughout the day.

Medicines

In 2015, the United States Public Health Service listed seven agents for the stopping of tobacco, which included five nicotine replacement treatments (nicotine patches, gum, lozenges, inhalers, and nasal sprays) and two oral medications (bupropion and varenicline). Other NRT options are available, including nicotine mouth sprays and sublingual tablets.

Dosing

The dose of nicotine replacement therapy products is generally based on if the user is considered a heavy, average, or light smoker.

Nicotine lozenges deliver doses as low as 1 mg up to 4 mg. It is not chewed as the gum would be, and dissolves in approximately 30 minutes. The inhaler may be preferred in individuals who want to satisfy the hand-to-mouth ritual that smoking provides. but they have not received FDA approval as smoking-cessation therapy aids that are safe and effective.

Snus and nasal snuff also allow for nicotine administration outside of tobacco smoking. Nicotine pouches are described as similar to or a tobacco-free variant of snus. They are pre-portioned and are held in the user's lip or cheek allowing for sublingual or buccal delivery of flavors and high doses of nicotine. The small pouches are not like chewing tobacco, as the user does not need to spit since the contents of the pouches stay inside during use. Swedish pouches have been available on the American consumer market since at least 2016 but their popularity and controversy surged in 2019 and 2020. In the US and UK concerns have been raised that nicotine pouches are seemingly too similar to banned snus products, is aimed at teenagers, further complicating the youth vaping trend, falling into the hands of adolescents easily, and are discrete enough to easily pass for regular gums or lozenges.

Nicotine infused toothpicks are another product that has been available in the United States since at least 2013. They can have a total nicotine delivery that is comparable to that of nicotine gum. In spite of these similarities, as of 2018 they have been a subject of controversy. Online retailers have been under scrutiny for allowing their products to be too easily purchased by youth. Various news outlets and school districts have expressed the concern that these products have a high appeal to minors wanting to experiment with nicotine due to; the multitude of sweet flavors offered, ease & speed of use, seeming innocuous, and having a discreet nature. In 2015, NRT sales fell for the first time since 2008 while sales for e-cigarettes or electronic nicotine delivery systems (ENDS) continued to increase at a substantial rate. The evidence is that UK smokers are trying to quit with e-cigarettes rather than NRT methods.

E-cigarettes are often, although not always, designed to look and feel like cigarettes. They have been marketed as less harmful alternatives to cigarettes, but very few are as yet approved as NRTs in any jurisdiction. Some electronic cigarettes have coarsely adjustable nicotine levels. Some healthcare groups have hesitated to recommend e-cigarettes for quitting smoking, because of limited evidence of effectiveness and safety. A 2014 study concluded that e-cigarettes appear to help smokers who were unable to stop smoking altogether to reduce their cigarette consumption when compared with placebo e-cigarettes and nicotine patches. Several studies have shown e-cigarettes to be the more effective tobacco smoking cessation tool in comparison to NRTs.

The U.S. Food and Drug Administration (FDA) has a list of additional tobacco products they are seeking to regulate, including electronic cigarettes. Most approved NRT products have been approved for over 20 years, however the FDA has also approved nicotine inhalers as a form of NRT. In 2024, the FDA cleared an investigational new drug (IND) application for a fast-acting inhalable NRT, which delivers nicotine without combustion or heating. 2025, the inhaler was successful in a first clinical trial, aiming to get approved by the FDA as the first smoking cessation drug since 2006.

Future approaches of NRT could include nicotine preloading, a true pulmonary inhaler, and nicotine vaccines.