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Nicotine is a naturally produced
alkaloid Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...
in the nightshade family of plants (most predominantly in
tobacco Tobacco is the common name of several plants in the genus '' Nicotiana'' of the family Solanaceae, and the general term for any product prepared from the cured leaves of these plants. More than 70 species of tobacco are known, but the ...
and ''
Duboisia hopwoodii ''Duboisia hopwoodii'' is a shrub native to the arid interior region of Australia. Common names include pituri, pitchuri thornapple or pitcheri. Description The species has an erect habit, usually growing to between 1 and 3 metres in height, wit ...
'') and is widely used recreationally as a stimulant and
anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...
. As a
pharmaceutical drug A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field an ...
, it is used for
smoking cessation Smoking cessation, usually called quitting smoking or stopping smoking, is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is addictive and can cause dependence. As a result, nicotine withdrawal often m ...
to relieve
withdrawal symptoms Drug withdrawal, drug withdrawal syndrome, or substance withdrawal syndrome, is the group of symptoms that occur upon the abrupt discontinuation or decrease in the intake of pharmaceutical or recreational drugs. In order for the symptoms of wit ...
. Nicotine acts as a
receptor agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an ...
at most
nicotinic acetylcholine receptor Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...
s (nAChRs), except at two
nicotinic receptor subunits Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...
(
nAChRα9 Neuronal acetylcholine receptor subunit alpha-9, also known as nAChRα9, is a protein that in humans is encoded by the ''CHRNA9'' gene. The protein encoded by this gene is a subunit of certain nicotinic acetylcholine receptors (nAchR). α9 subuni ...
and nAChRα10) where it acts as a receptor antagonist. Nicotine constitutes approximately 0.6–3.0% of the dry weight of tobacco. Nicotine is also present at ppb-concentrations in edible plants in the family Solanaceae, including
potato The potato is a starchy food, a tuber of the plant ''Solanum tuberosum'' and is a root vegetable native to the Americas. The plant is a perennial in the nightshade family Solanaceae. Wild potato species can be found from the southern Unit ...
es,
tomato The tomato is the edible berry of the plant ''Solanum lycopersicum'', commonly known as the tomato plant. The species originated in western South America, Mexico, and Central America. The Mexican Nahuatl word gave rise to the Spanish word ...
es, and eggplants, though sources disagree on whether this has any biological significance to human consumers. It functions as an antiherbivore toxin; consequently, nicotine was widely used as an insecticide in the past, and
neonicotinoids Neonicotinoids (sometimes shortened to neonics ) are a class of neuro-active insecticides chemically similar to nicotine, developed by scientists at Shell and Bayer in the 1980s. The neonicotinoid family includes acetamiprid, clothianidin, din ...
(structurally similar to nicotine), such as
imidacloprid Imidacloprid is a systemic insecticide belonging to a class of chemicals called the neonicotinoids which act on the central nervous system of insects. The chemical works by interfering with the transmission of stimuli in the insect nervous system ...
, are some of the most effective and widely used insecticides. Nicotine is highly addictive. Slow-release forms (gums and patches, when used correctly) are less addictive and aid in quitting. Animal research suggests that
monoamine oxidase inhibitors Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, espec ...
present in tobacco smoke may enhance nicotine's addictive properties. An average cigarette yields about 2 mg of absorbed nicotine. The estimated lower dose limit for fatal outcomes is 500–1,000 mg of ingested nicotine for an adult (6.5–13 mg/kg). Nicotine addiction involves drug-reinforced behavior, compulsive use, and relapse following abstinence. Nicotine dependence involves tolerance, sensitization,
physical dependence Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certai ...
,
psychological dependence Psychological dependence is a cognitive disorder that involves emotional–motivational withdrawal symptoms—e.g. anxiety and anhedonia—upon cessation of prolonged drug abuse or certain repetitive behaviors. It develops through frequent exp ...
, and can cause distress. Nicotine withdrawal symptoms include depressed mood, stress, anxiety, irritability, difficulty concentrating, and sleep disturbances. Mild nicotine withdrawal symptoms are measurable in unrestricted smokers, who experience normal moods only as their blood nicotine levels peak, with each cigarette. On quitting, withdrawal symptoms worsen sharply, then gradually improve to a normal state. Nicotine use as a tool for
quitting smoking Smoking cessation, usually called quitting smoking or stopping smoking, is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is addictive and can cause dependence. As a result, nicotine withdrawal often make ...
has a good safety history. Animal studies suggest that nicotine may adversely affect cognitive development in adolescence, but the relevance of these findings to human brain development is disputed. At low amounts, it has a mild analgesic effect. According to the
International Agency for Research on Cancer The International Agency for Research on Cancer (IARC; french: Centre International de Recherche sur le Cancer, CIRC) is an intergovernmental agency forming part of the World Health Organization of the United Nations. Its role is to conduct and ...
, "nicotine is not generally considered to be a carcinogen." The Surgeon General of the United States indicates that evidence is inadequate to infer the presence or absence of a causal relationship between exposure to nicotine and risk for cancer. Nicotine has been shown to produce birth defects in humans and is considered a teratogen. The median lethal dose of nicotine in humans is unknown. High doses are known to cause
nicotine poisoning Nicotine poisoning describes the symptoms of the toxic effects of nicotine following ingestion, inhalation, or skin contact. Nicotine poisoning can potentially be deadly, though serious or fatal overdoses are rare. Historically, most cases of nicot ...
, organ failure, and death through paralysis of respiratory muscles, though serious or fatal overdoses are rare.


Uses


Medical

The primary therapeutic use of nicotine is treating nicotine dependence to eliminate smoking and the damage it does to health. Controlled levels of nicotine are given to patients through
gums The gums or gingiva (plural: ''gingivae'') consist of the mucosal tissue that lies over the mandible and maxilla inside the mouth. Gum health and disease can have an effect on general health. Structure The gums are part of the soft tissue lin ...
, dermal patches, lozenges, inhalers, or nasal sprays to wean them off their dependence. A 2018
Cochrane Collaboration Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profess ...
review found high-quality evidence that all current forms of nicotine replacement therapy (gum, patch, lozenges, inhaler, and nasal spray) therapies increase the chances of successfully quitting smoking by , regardless of setting. Combining
nicotine patch A nicotine patch is a transdermal patch that releases nicotine into the body through the skin. It is used in nicotine replacement therapy (NRT), a process for smoking cessation. Endorsed and approved by the U.S. Food and Drug Administration (FDA) ...
use with a faster acting nicotine replacement, like gum or spray, improves the odds of treatment success. 4 mg versus 2 mg nicotine gum also increase the chances of success. Nicotine is being researched in clinical trials for possible benefit in treating
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
,
dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
, ADHD, depression and
sarcoma A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal ( connective tissue) origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sar ...
. In contrast to recreational nicotine products, which have been designed to maximize the likelihood of addiction, nicotine replacement products (NRTs) are designed to minimize addictiveness. The more quickly a dose of nicotine is delivered and absorbed, the higher the addiction risk.


Pesticide

Nicotine has been used as an insecticide since at least the 1690s, in the form of tobacco extracts (although other components of tobacco also seem to have pesticide effects). Nicotine pesticides have not been commercially available in the US since 2014, and homemade pesticides are banned on organic cropsUS Code of Federal Regulations
7 CFR 205.602 – Nonsynthetic substances prohibited for use in organic crop production
/ref> and not recommended for small gardeners. Nicotine pesticides have been banned in the EU since 2009. Foods are imported from countries in which nicotine pesticides are allowed, such as China, but foods may not exceed maximum nicotine levels.
Neonicotinoids Neonicotinoids (sometimes shortened to neonics ) are a class of neuro-active insecticides chemically similar to nicotine, developed by scientists at Shell and Bayer in the 1980s. The neonicotinoid family includes acetamiprid, clothianidin, din ...
, which are derived from and structurally similar to nicotine, are widely used as agricultural and veterinary pesticides as of 2016. In nicotine-producing plants, nicotine functions as an antiherbivory chemical; consequently, nicotine has been widely used as an insecticide, and
neonicotinoids Neonicotinoids (sometimes shortened to neonics ) are a class of neuro-active insecticides chemically similar to nicotine, developed by scientists at Shell and Bayer in the 1980s. The neonicotinoid family includes acetamiprid, clothianidin, din ...
, such as
imidacloprid Imidacloprid is a systemic insecticide belonging to a class of chemicals called the neonicotinoids which act on the central nervous system of insects. The chemical works by interfering with the transmission of stimuli in the insect nervous system ...
, are widely used.


Performance

Nicotine-containing products are sometimes used for the performance-enhancing effects of nicotine on cognition. A 2010 meta-analysis of 41 
double-blind In a blind or blinded experiment, information which may influence the participants of the experiment is withheld until after the experiment is complete. Good blinding can reduce or eliminate experimental biases that arise from a participants' expec ...
,
placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. In general, placebos can af ...
-controlled studies concluded that nicotine or smoking had significant positive effects on aspects of fine motor abilities, alerting and orienting attention, and episodic and working memory. A 2015 review noted that stimulation of the α4β2 nicotinic receptor is responsible for certain improvements in attentional performance; among the nicotinic receptor subtypes, nicotine has the highest
binding affinity In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a m ...
at the α4β2 receptor (ki=1 ), which is also the biological target that mediates nicotine's addictive properties. Nicotine has potential beneficial effects, but it also has
paradoxical effects A paradoxical reaction (or paradoxical effect) is an effect of a chemical substance, such as a medical drug, that is opposite to what would usually be expected. An example of a paradoxical reaction is pain caused by a pain relief medication. Parad ...
, which may be due to the inverted U-shape of the dose-response curve or pharmacokinetic features.


Recreational

Nicotine is used as a recreational drug. It is widely used, highly addictive and hard to discontinue. Nicotine is often used compulsively, and dependence can develop within days. Recreational drug users commonly use nicotine for its mood-altering effects. Recreational nicotine products include
chewing tobacco Chewing tobacco is a type of smokeless tobacco product that is placed between the cheek and lower gum to draw out its flavor. Some users chew it, others do not. It consists of coarsely chopped aged tobacco that is flavored and often sweetened; ...
,
cigars A cigar is a rolled bundle of dried and fermented tobacco leaves made to be smoked. Cigars are produced in a variety of sizes and shapes. Since the 20th century, almost all cigars are made of three distinct components: the filler, the binder le ...
,
cigarettes A cigarette is a narrow cylinder containing a combustible material, typically tobacco, that is rolled into thin paper for smoking. The cigarette is ignited at one end, causing it to smolder; the resulting smoke is orally inhaled via the opp ...
,
e-cigarettes An electronic cigarette is an electronic device that simulates tobacco smoking. It consists of an atomizer, a power source such as a battery, and a container such as a cartridge or tank. Instead of smoke, the user inhales vapor. As such ...
,
snuff Snuff may refer to: Tobacco * Snuff (tobacco), fine-ground tobacco, sniffed into the nose ** Moist snuff or dipping tobacco ** Creamy snuff, an Indian tobacco paste Media and entertainment * Snuff film, a type of film that shows a murder Literat ...
,
pipe tobacco A tobacco pipe, often called simply a pipe, is a device specifically made to smoke tobacco. It comprises a chamber (the bowl) for the tobacco from which a thin hollow stem (shank) emerges, ending in a mouthpiece. Pipes can range from very simp ...
, and
snus Snus ( , ) is a tobacco product, originating from a variant of dry snuff in early 18th-century Sweden. It is placed between the upper lip and gum for extended periods, as a form of sublabial administration. Snus is not fermented. Although used ...
. Alcohol infused with nicotine is called nicotini.


Contraindications

Nicotine use for tobacco cessation has few contraindications. It is not known whether nicotine replacement therapy is effective for smoking cessation in adolescents, as of 2014. It is therefore not recommended to adolescents. It is not safe to use nicotine during pregnancy or breastfeeding, although it is safer than smoking; the desirability of NRT use in pregnancy is therefore debated. Randomized trials and observational studies of nicotine replacement therapy in cardiovascular patients show no increase in adverse cardiovascular events compared to those treated with placebo. Using nicotine products during cancer treatment is counterrecommended, as nicotine promotes tumour growth, but temporary use of NRTs to quit smoking may be advised for
harm reduction Harm reduction, or harm minimization, refers to a range of public health policies designed to lessen the negative social and/or physical consequences associated with various human behaviors, both legal and illegal. Harm reduction is used to d ...
.
Nicotine gum Nicotine gum is a type of chewing gum that delivers nicotine to the body. It is used as an aid in nicotine replacement therapy (NRT), a process for smoking cessation and quitting smokeless tobacco. The nicotine is delivered to the bloodstream via ...
is contraindicated in individuals with temporomandibular joint disease. People with chronic nasal disorders and severe reactive airway disease require additional precautions when using nicotine nasal sprays. Nicotine in any form is
contraindicated In medicine, a contraindication is a condition that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a reason to use a certain tre ...
in individuals with a known
hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune ...
to nicotine.


Adverse effects

Nicotine is classified as a poison. However, at doses used by consumers, it presents little if any hazard to the user. A 2018
Cochrane Collaboration Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profess ...
review lists nine main adverse events related to nicotine replacement therapy: headache, dizziness/light-headedness, nausea/vomiting, gastro-intestinal symptoms, sleep/dream problems, non-
ischemic Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems w ...
palpitations and chest pain, skin reactions, oral/nasal reactions and hiccups. Many of these were also common in the placebo group without nicotine. Palpitations and chest pain were deemed "rare" and there was no evidence of an increased number of serious cardiac problems compared to the placebo group, even in people with established cardiac disease. The common side effects from nicotine exposure are listed in the table below. Serious adverse events due to the use of nicotine replacement therapy are extremely rare. At low amounts, it has a mild analgesic effect. At sufficiently high doses, nicotine may result in nausea, vomiting, diarrhea, salivation, bradyarrhythmia, and possibly seizures, hypoventilation, and death.


Sleep

Nicotine reduces the amount of rapid eye movement (REM) sleep,
slow-wave sleep Slow-wave sleep (SWS), often referred to as deep sleep, consists of stage three of non-rapid eye movement sleep. It usually lasts between 70 and 90 minutes and takes place during the first hours of the night. Initially, SWS consisted of both St ...
(SWS), and total sleep time in healthy nonsmokers given nicotine via a
transdermal patch A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream. An advantage of a transdermal drug delivery route over other types of medica ...
, and the reduction is dose-dependent. Acute nicotine intoxication has been found to significantly reduce total sleep time and increase REM latency,
sleep onset latency In sleep science, sleep onset latency (SOL) is the length of time that it takes to accomplish the transition from full wakefulness to sleep, normally to the lightest of the non-REM sleep stages. Sleep latency studies Pioneering Stanford Univers ...
, and non-rapid eye movement (NREM) stage 2 sleep time. Depressive non-smokers experience mood and sleep improvements under nicotine administration; however, subsequent nicotine withdrawal has a negative effect on both mood and sleep.


Cardiovascular system

A 2018 Cochrane review found that, in rare cases, nicotine replacement therapy can cause non-
ischemic Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems w ...
chest pain (i.e., chest pain that is unrelated to a
heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which ma ...
) and
heart palpitation Palpitations are perceived abnormalities of the heartbeat characterized by awareness of cardiac muscle contractions in the chest, which is further characterized by the hard, fast and/or irregular beatings of the heart. Symptoms include a rap ...
s, but does not increase the incidence of serious cardiac adverse events (i.e., myocardial infarction, stroke, and cardiac death) relative to controls. A 2016 review of the cardiovascular toxicity of nicotine concluded, "Based on current knowledge, we believe that the cardiovascular risks of nicotine from e-cigarette use in people without cardiovascular disease are quite low. We have concerns that nicotine from e-cigarettes could pose some risk for users with cardiovascular disease."


Blood pressure

In the short term, nicotine causes a transient increase in blood pressure, but in the long term, epidemiological studies generally do not show increased blood pressure or hypertension among nicotine users.


Reinforcement disorders

Nicotine is highly addictive. Its addictiveness depends on how it is administered. Animal research suggests that
monoamine oxidase inhibitors Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, espec ...
in tobacco smoke may enhance its addictiveness.
Nicotine dependence Nicotine dependence is a state of dependence upon nicotine. Nicotine dependence is a chronic, relapsing disease defined as a compulsive craving to use the drug, despite social consequences, loss of control over drug intake, and emergence of wit ...
involves aspects of both
psychological dependence Psychological dependence is a cognitive disorder that involves emotional–motivational withdrawal symptoms—e.g. anxiety and anhedonia—upon cessation of prolonged drug abuse or certain repetitive behaviors. It develops through frequent exp ...
and
physical dependence Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certai ...
, since discontinuation of extended use has been shown to produce both
affective Affect, in psychology, refers to the underlying experience of feeling, emotion or mood. History The modern conception of affect developed in the 19th century with Wilhelm Wundt. The word comes from the German ''Gefühl'', meaning "feeling. ...
(e.g., anxiety, irritability, craving,
anhedonia Anhedonia is a diverse array of deficits in hedonic function, including reduced motivation or ability to experience pleasure. While earlier definitions emphasized the inability to experience pleasure, anhedonia is currently used by researchers t ...
) and somatic (mild motor dysfunctions such as tremor) withdrawal symptoms. Withdrawal symptoms peak in one to three days and can persist for several weeks. Some people experience symptoms for 6 months or longer. Normal between-cigarettes discontinuation, in unrestricted smokers, causes mild but measurable nicotine withdrawal symptoms. These include mildly worse mood, stress, anxiety, cognition, and sleep, all of which briefly return to normal with the next cigarette. Smokers have worse mood than they would have if they were not nicotine-dependent; they experience normal moods only immediately after smoking. Nicotine dependence is associated with poor sleep quality and shorter sleep duration among smokers. In dependent smokers, withdrawal causes impairments in memory and attention, and smoking during withdrawal returns these cognitive abilities to pre-withdrawal levels. The temporarily increased cognitive levels of smokers after inhaling smoke are offset by periods of cognitive decline during nicotine withdrawal. Therefore, the overall daily cognitive levels of smokers and non-smokers are roughly similar. Nicotine activates the
mesolimbic pathway The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmentum, ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the for ...
and
induces Electromagnetic or magnetic induction is the production of an electromotive force (emf) across an electrical conductor in a changing magnetic field. Michael Faraday is generally credited with the discovery of induction in 1831, and James Cler ...
long-term
ΔFosB Protein fosB, also known as FosB and G0/G1 switch regulatory protein 3 (G0S3), is a protein that in humans is encoded by the FBJ murine osteosarcoma viral oncogene homolog B (''FOSB'') gene. The FOS gene family consists of four members: FOS, F ...
expression (i.e., produces
phosphorylated In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
ΔFosB
isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some iso ...
s) in the
nucleus accumbens The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for " nucleus adjacent to the septum") is a region in the basal forebrain rostral to the preoptic area of the hypot ...
when inhaled or injected frequently or at high doses, but not necessarily when ingested. Consequently, high daily exposure (possibly excluding oral route) to nicotine can cause ΔFosB overexpression in the nucleus accumbens, resulting in nicotine addiction.


Cancer

Although nicotine itself does not cause cancer in humans, it is unclear whether it functions as a tumor promoter . A 2018 report by the US National Academies of Sciences, Engineering, and Medicine concludes, " ile it is biologically plausible that nicotine can act as a tumor promoter, the existing body of evidence indicates this is unlikely to translate into increased risk of human cancer." Low levels of nicotine stimulate cell proliferation, while high levels are cytotoxic. Nicotine increases
cholinergic Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word " choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cati ...
signaling and
adrenergic Adrenergic means "working on adrenaline (epinephrine) or noradrenaline (norepinephrine)" (or on their receptors). When not further qualified, it is usually used in the sense of enhancing or mimicking the effects of epinephrine and norepinephrine ...
signaling in colon cancer cells, thereby impeding apoptosis (
programmed cell death Programmed cell death (PCD; sometimes referred to as cellular suicide) is the death of a cell (biology), cell as a result of events inside of a cell, such as apoptosis or autophagy. PCD is carried out in a biological process, which usually confers ...
), promoting tumor growth, and activating
growth factors A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for reg ...
and cellular
mitogenic A mitogen is a small bioactive protein or peptide that induces a cell to begin cell division, or enhances the rate of division (mitosis). Mitogenesis is the induction (triggering) of mitosis, typically via a mitogen. The mechanism of action of a ...
factors such as 5-lipoxygenase (5-LOX), and epidermal growth factor (EGF). Nicotine also promotes cancer growth by stimulating angiogenesis and
neovascularization Neovascularization is the natural formation of new blood vessels ('' neo-'' + '' vascular'' + '' -ization''), usually in the form of functional microvascular networks, capable of perfusion by red blood cells, that form to serve as collateral circu ...
. Nicotine promotes lung cancer development and accelerates its proliferation, angiogenesis, migration, invasion and epithelial–mesenchymal transition (EMT), via its influence on nAChRs receptors, whose presence has been confirmed in lung cancer cells. In cancer cells, nicotine promotes the
epithelial–mesenchymal transition The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell–cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells; these are multipotent stromal ...
which makes the cancer cells more resistant to drugs that treat cancer. Nicotine in tobacco can form carcinogenic
tobacco-specific nitrosamines Tobacco-specific nitrosamines (TSNAs) comprise one of the most important groups of carcinogens in tobacco products, particularly cigarettes (traditional and electronic) and fermented dipping snuff. Background These nitrosamine carcinogens are fo ...
through a
nitrosation Nitrosation is a process of converting organic compounds into nitroso derivatives, i.e. compounds containing the R-NO functionality. ''C''-Nitroso compounds ''C''-Nitroso compounds, such as nitrosobenzene, are typically prepared by oxidation of ...
reaction. This occurs mostly in the curing and processing of tobacco. However, nicotine in the mouth and stomach can react to form
N-Nitrosonornicotine ''N''-Nitrosonornicotine (NNN) is a tobacco-specific nitrosamine produced during the curing and processing of tobacco. Toxicity It has been classified as a Group 1 carcinogen. Although no adequate studies of the relationship between exposure t ...
, a known type 1 carcinogen, suggesting that consumption of non-tobacco forms of nicotine may still play a role in carcinogenesis.


Genotoxicity

Nicotine causes
DNA damage DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA d ...
in several types of human cells as judged by assays for
genotoxicity Genotoxicity is the property of chemical agents that damage the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with mutagenicity, all mutagens are genotoxic, but some genotoxic su ...
such as the comet assay, cytokinesis-block micronucleus test and chromosome aberrations test. In humans, this damage can happen in primary
parotid gland The parotid gland is a major salivary gland in many animals. In humans, the two parotid glands are present on either side of the mouth and in front of both ears. They are the largest of the salivary glands. Each parotid is wrapped around the ma ...
cells,
lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...
s, respiratory tract cells.


Pregnancy and breastfeeding

Nicotine has been shown to produce birth defects in some animal species, but not others; consequently, it is considered to be a possible teratogen in humans. In
animal studies Animal studies is a recently recognised field in which animals are studied in a variety of cross-disciplinary ways. Scholars who engage in animal studies may be formally trained in a number of diverse fields, including geography, art history, ant ...
that resulted in birth defects, researchers found that nicotine negatively affects fetal
brain development The development of the nervous system, or neural development (neurodevelopment), refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. The fiel ...
and pregnancy outcomes; the negative effects on early brain development are associated with abnormalities in brain metabolism and
neurotransmitter system A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neur ...
function. Nicotine crosses the
placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mate ...
and is found in the breast milk of mothers who smoke as well as mothers who inhale
passive smoke Passive smoking is the inhalation of tobacco smoke, called secondhand smoke (SHS), or environmental tobacco smoke (ETS), by persons other than the intended "active" smoker. It occurs when tobacco smoke enters an environment, causing its inhalat ...
. Nicotine exposure ''
in utero ''In Utero'' is the third and final studio album by American rock band Nirvana. It was released on September 21, 1993, by DGC Records. After breaking into the mainstream with their second album, ''Nevermind'' (1991), Nirvana hired Steve Albin ...
'' is responsible for several complications of pregnancy and birth: pregnant women who smoke are at greater risk for both miscarriage and stillbirth and infants exposed to nicotine ''in utero'' tend to have lower
birth weight Birth weight is the body weight of a baby at its birth. The average birth weight in babies of European descent is , with the normative range between . On average, babies of South Asian and Chinese descent weigh about . As far as low birth weigh ...
s. A
McMaster University McMaster University (McMaster or Mac) is a public research university in Hamilton, Ontario, Canada. The main McMaster campus is on of land near the residential neighbourhoods of Ainslie Wood and Westdale, adjacent to the Royal Botanical Ga ...
research group observed in 2010 that rats exposed to nicotine in the womb (via parenteral infusion) later in life had conditions including
type 2 diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urinatio ...
,
obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
, hypertension, neurobehavioral defects, respiratory dysfunction, and infertility.


Overdose

It is unlikely that a person would overdose on nicotine through smoking alone. The US
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) stated in 2013 that there are no significant safety concerns associated with the use of more than one form of
over-the-counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...
(OTC)
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 ...
at the same time, or using OTC NRT at the same time as another nicotine-containing product, like cigarettes. The median lethal dose of nicotine in humans is unknown. Nevertheless, nicotine has a relatively high
toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subs ...
in comparison to many other alkaloids such as
caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. It is mainly used recreationally as a cognitive enhancer, increasing alertness and attentional performance. Caffeine acts by blocking binding of adenosine to ...
, which has an LD50 of 127 mg/kg when administered to mice. At sufficiently high doses, it is associated with nicotine poisoning, which, while common in children (in whom poisonous and lethal levels occur at lower doses per kilogram of body weight) rarely results in significant morbidity or death. The estimated lower dose limit for fatal outcomes is 500–1,000 mg of ingested nicotine for an adult (6.5–13 mg/kg). The initial symptoms of a nicotine overdose typically include
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
, vomiting, diarrhea,
hypersalivation Hypersalivation, or ptyalism, also known as sialorrhea or hypersialosis is the excessive production of saliva. It has also been defined as increased amount of saliva in the mouth, which may also be caused by decreased clearance of saliva.Medscape ...
, abdominal pain,
tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...
(rapid heart rate), hypertension (high blood pressure),
tachypnea Tachypnea, also spelt tachypnoea, is a respiratory rate greater than normal, resulting in abnormally rapid and shallow breathing. In adult humans at rest, any respiratory rate of 1220 per minute is considered clinically normal, with tachypnea b ...
(rapid breathing), headache, dizziness, pallor (pale skin), auditory or visual disturbances, and perspiration, followed shortly after by marked bradycardia (slow heart rate), bradypnea (slow breathing), and
hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...
(low blood pressure). Respiratory stimulation (i.e., tachypnea) is one of the primary signs of nicotine poisoning. At sufficiently high doses,
somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...
(sleepiness or drowsiness),
confusion In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion"
, syncope (loss of consciousness from fainting),
shortness of breath Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing di ...
, marked
weakness Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...
,
seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...
s, and coma may occur. Lethal nicotine poisoning rapidly produces seizures, and death – which may occur within minutes – is believed to be due to
respiratory paralysis Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a rise ...
.


Toxicity

Today nicotine is less commonly used in agricultural insecticides, which was a main source of poisoning. More recent cases of poisoning typically appear to be in the form of Green Tobacco Sickness, accidental ingestion of
tobacco Tobacco is the common name of several plants in the genus '' Nicotiana'' of the family Solanaceae, and the general term for any product prepared from the cured leaves of these plants. More than 70 species of tobacco are known, but the ...
or
tobacco products Tobacco is the agricultural product of the leaves of plants in the genus ''Nicotiana'', commonly termed ''tobacco plants''. All species of ''Nicotiana'' contain the addictive drug nicotine—a psychostimulant alkaloid found in all parts of the ...
, or ingestion of nicotine-containing plants. People who harvest or cultivate tobacco may experience Green Tobacco Sickness (GTS), a type of nicotine poisoning caused by dermal exposure to wet tobacco leaves. This occurs most commonly in young, inexperienced tobacco harvesters who do not consume tobacco. People can be exposed to nicotine in the workplace by breathing it in, skin absorption, swallowing it, or eye contact. The
Occupational Safety and Health Administration The Occupational Safety and Health Administration'' (OSHA ) is a large regulatory agency of the United States Department of Labor that originally had federal visitorial powers to inspect and examine workplaces. Congress established the agenc ...
(OSHA) has set the legal limit (
permissible exposure limit The permissible exposure limit (PEL or OSHA PEL) is a legal limit in the United States for exposure of an employee to a chemical substance or physical agent such as high level noise. Permissible exposure limits are established by the Occupational ...
) for nicotine exposure in the workplace as 0.5 mg/m3 skin exposure over an 8-hour workday. The US
National Institute for Occupational Safety and Health The National Institute for Occupational Safety and Health (NIOSH, ) is the United States federal agency responsible for conducting research and making recommendations for the prevention of work-related injury and illness. NIOSH is part of the C ...
(NIOSH) has set a
recommended exposure limit A recommended exposure limit (REL) is an occupational exposure limit that has been recommended by the United States National Institute for Occupational Safety and Health. The REL is a level that NIOSH believes would be protective of worker safet ...
(REL) of 0.5 mg/m3 skin exposure over an 8-hour workday. At environmental levels of 5 mg/m3, nicotine is
immediately dangerous to life and health The term immediately dangerous to life or health (IDLH) is defined by the US National Institute for Occupational Safety and Health (NIOSH) as exposure to airborne contaminants that is "likely to cause death or immediate or delayed permanent advers ...
.


Drug interactions


Pharmacodynamic

* Potential interaction with
sympathomimetic drug Sympathomimetic drugs (also known as adrenergic drugs and adrenergic amines) are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. Examples of sympathomimetic effects include increases in heart ...
s ( adrenergic agonists) and sympatholytic drugs ( alpha-blockers and beta-blockers).


Pharmacokinetic

Nicotine and cigarette smoke both induce the
expression Expression may refer to: Linguistics * Expression (linguistics), a word, phrase, or sentence * Fixed expression, a form of words with a specific meaning * Idiom, a type of fixed expression * Metaphorical expression, a particular word, phrase, o ...
of liver enzymes (e.g., certain
cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...
proteins) which metabolize drugs, leading to the potential for alterations in
drug metabolism Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set o ...
. * ''Smoking cessation'' may decrease the metabolism of acetaminophen, beta-blockers,
caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. It is mainly used recreationally as a cognitive enhancer, increasing alertness and attentional performance. Caffeine acts by blocking binding of adenosine to ...
,
oxazepam Oxazepam is a short-to-intermediate-acting benzodiazepine. Oxazepam is used for the treatment of anxiety and insomnia and in the control of symptoms of alcohol withdrawal syndrome. It is a metabolite of diazepam, prazepam, and temazepam, and ha ...
,
pentazocine Pentazocine, sold under the brand name Talwin among others, is a painkiller used to treat moderate to severe pain. It is believed to work by activating (agonizing) κ-opioid receptors (KOR) and μ-opioid receptors (MOR). As such it is called an ...
,
propoxyphene Dextropropoxyphene is an analgesic in the opioid category, patented in 1955 and manufactured by Eli Lilly and Company. It is an optical isomer of levopropoxyphene. It is intended to treat mild pain and also has antitussive (cough suppressant) ...
,
theophylline Theophylline, also known as 1,3-dimethylxanthine, is a phosphodiesterase inhibiting drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma under a variety of brand names. As a member of the ...
, and
tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...
, leading to higher plasma concentrations of these drugs. * Possible alteration of nicotine absorption through the skin from the transdermal nicotine patch by drugs that cause
vasodilation Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstrictio ...
or
vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vess ...
. * Possible alteration of nicotine absorption through the nasal cavity from the nicotine nasal spray by nasal vasoconstrictors (e.g.,
xylometazoline Xylometazoline, also spelled xylomethazoline, is a medication used to reduce symptoms of nasal congestion, allergic rhinitis, and sinusitis. Use is not recommended for more than seven days. Use is also not recommended in those less than three m ...
). * Possible alteration of nicotine absorption through
oral mucosa The oral mucosa is the mucous membrane lining the inside of the mouth. It comprises stratified squamous epithelium, termed "oral epithelium", and an underlying connective tissue termed '' lamina propria''. The oral cavity has sometimes been des ...
from nicotine gum and lozenges by food and drink that modify salivary pH.


Pharmacology


Pharmacodynamics

Nicotine acts as a
receptor agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an ...
at most
nicotinic acetylcholine receptor Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...
s (nAChRs), except at two
nicotinic receptor subunits Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...
(
nAChRα9 Neuronal acetylcholine receptor subunit alpha-9, also known as nAChRα9, is a protein that in humans is encoded by the ''CHRNA9'' gene. The protein encoded by this gene is a subunit of certain nicotinic acetylcholine receptors (nAchR). α9 subuni ...
and nAChRα10) where it acts as a receptor antagonist. Such antagonism results in mild
analgesia Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professional ...
.


Central nervous system

By binding to
nicotinic acetylcholine receptor Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...
s in the brain, nicotine elicits its psychoactive effects and increases the levels of several neurotransmitters in various brain structures – acting as a sort of "volume control". Nicotine has a higher affinity for nicotinic receptors in the brain than those in skeletal muscle, though at toxic doses it can induce contractions and respiratory paralysis. Nicotine's selectivity is thought to be due to a particular amino acid difference on these receptor subtypes. Nicotine is unusual in comparison to most drugs, as its profile changes from stimulant to sedative with increasing dosages, a phenomenon known as "Nesbitt's paradox" after the doctor who first described it in 1969. At very high doses it dampens
neuronal activity Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron), ...
. Nicotine induces both behavioral stimulation and anxiety in animals. Research into nicotine's most predominant metabolite, cotinine, suggests that some of nicotine's psychoactive effects are mediated by cotinine. Nicotine activates nicotinic receptors (particularly α4β2 nicotinic receptors, but also α5 nAChRs) on neurons that innervate the
ventral tegmental area The ventral tegmental area (VTA) (tegmentum is Latin for ''covering''), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is th ...
and within the
mesolimbic pathway The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmentum, ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the for ...
where it appears to cause the release of dopamine. This nicotine-induced dopamine release occurs at least partially through activation of the cholinergic–dopaminergic reward link in the
ventral tegmental area The ventral tegmental area (VTA) (tegmentum is Latin for ''covering''), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is th ...
. Nicotine can modulate the firing rate of the ventral tegmental area neurons. Nicotine also appears to induce the release of
endogenous opioid Opioid peptides are peptides that bind to opioid receptors in the brain; opiates and opioids mimic the effect of these peptides. Such peptides may be produced by the body itself, for example endorphins. The effects of these peptides vary, but t ...
s that activate opioid pathways in the reward system, since
naltrexone Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been foun ...
 – an
opioid receptor antagonist An opioid antagonist, or opioid receptor antagonist, is a receptor antagonist that acts on one or more of the opioid receptors. Naloxone and naltrexone are commonly used opioid antagonist drugs which are competitive antagonists that bind to the o ...
 – blocks nicotine self-administration. These actions are largely responsible for the strongly reinforcing effects of nicotine, which often occur in the absence of euphoria; however, mild euphoria from nicotine use can occur in some individuals. Chronic nicotine use inhibits class I and II
histone deacetylases Histone deacetylases (, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly. This is important because DNA is wrapped around his ...
in the striatum, where this effect plays a role in nicotine addiction.


Sympathetic nervous system

Nicotine also activates the sympathetic nervous system, acting via
splanchnic nerves The splanchnic nerves are paired visceral nerves (nerves that contribute to the innervation of the internal organs), carrying fibers of the autonomic nervous system ( visceral efferent fibers) as well as sensory fibers from the organs ( visceral ...
to the adrenal medulla, stimulating the release of epinephrine. Acetylcholine released by preganglionic sympathetic fibers of these nerves acts on nicotinic acetylcholine receptors, causing the release of epinephrine (and norepinephrine) into the
bloodstream The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
.


Adrenal medulla

By binding to
ganglion type nicotinic receptor The alpha-3 beta-4 nicotinic receptor, also known as the α3β4 receptor and the ganglion-type nicotinic receptor,Pharmacology, (Rang, Dale, Ritter & Moore, , 5th ed., Churchill Livingstone 2003) p. 138. is a type of nicotinic acetylcholine receptor ...
s in the adrenal medulla, nicotine increases flow of
adrenaline Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands an ...
(epinephrine), a stimulating
hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are require ...
and neurotransmitter. By binding to the receptors, it causes cell depolarization and an influx of
calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...
through voltage-gated calcium channels. Calcium triggers the exocytosis of chromaffin granules and thus the release of epinephrine (and norepinephrine) into the
bloodstream The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
. The release of epinephrine (adrenaline) causes an increase in
heart rate Heart rate (or pulse rate) is the frequency of the heartbeat measured by the number of contractions (beats) of the heart per minute (bpm). The heart rate can vary according to the body's physical needs, including the need to absorb oxygen and excr ...
, blood pressure and
respiration Respiration may refer to: Biology * Cellular respiration, the process in which nutrients are converted into useful energy in a cell ** Anaerobic respiration, cellular respiration without oxygen ** Maintenance respiration, the amount of cellul ...
, as well as higher
blood glucose Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the blo ...
levels.


Pharmacokinetics

As nicotine enters the body, it is distributed quickly through the
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
stream and crosses the blood–brain barrier reaching the
brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...
within 10–20 seconds after inhalation. The
elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...
of nicotine in the body is around two hours. Nicotine is primarily
excreted Excretion is a process in which metabolic waste is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after lea ...
in
urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular ...
and urinary concentrations vary depending upon urine flow rate and
urine pH Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular m ...
. The amount of nicotine absorbed by the body from smoking can depend on many factors, including the types of tobacco, whether the smoke is inhaled, and whether a filter is used. However, it has been found that the nicotine yield of individual products has only a small effect (4.4%) on the blood concentration of nicotine, suggesting "the assumed health advantage of switching to lower-tar and lower-nicotine cigarettes may be largely offset by the tendency of smokers to compensate by increasing inhalation". Nicotine has a half-life of 1–2 hours. Cotinine is an active metabolite of nicotine that remains in the blood with a half-life of 18–20 hours, making it easier to analyze. Nicotine is
metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
in the
liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
by
cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...
enzymes (mostly CYP2A6, and also by
CYP2B6 Cytochrome P450 2B6 is an enzyme that in humans is encoded by the ''CYP2B6'' gene. CYP2B6 is a member of the cytochrome P450 group of enzymes. Along with CYP2A6, it is involved with metabolizing nicotine, along with many other substances. Funct ...
) and
FMO3 Flavin-containing monooxygenase 3 (FMO3), also known as dimethylaniline monooxygenase -oxide-forming3 and trimethylamine monooxygenase, is a flavoprotein enzyme () that in humans is encoded by the ''FMO3'' gene. This enzyme catalyzes the follow ...
, which selectively metabolizes (''S'')-nicotine. A major metabolite is cotinine. Other primary metabolites include nicotine ''N-oxide, nornicotine, nicotine isomethonium ion, 2-hydroxynicotine and nicotine glucuronide. Under some conditions, other substances may be formed such as
myosmine Myosmine is an alkaloid found in tobacco and other plants. Chemically, it is closely related to nicotine. It inhibits aromatase seven fold more potently than nicotine. It also releases dopamine in adult but not adolescent rats. See also * Cath ...
.
Glucuronidation Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve gl ...
and oxidative metabolism of nicotine to cotinine are both inhibited by menthol, an additive to mentholated cigarettes, thus increasing the half-life of nicotine ''in vivo''.


Metabolism

Nicotine decreases hunger and food consumption. The majority of research shows that nicotine reduces body weight, but some researchers have found that nicotine may result in weight gain under specific types of eating habits in animal models. Nicotine effect on weight appears to result from nicotine's stimulation of α3β4 nAChR receptors located in the POMC neurons in the arcuate nucleus and subsequently the melanocortin system, especially the melanocortin-4 receptors on second-order neurons in the paraventricular nucleus of the hypothalamus, thus modulating feeding inhibition. POMC neurons are a precursor of the melanocortin system, a critical regulator of body weight and peripheral tissue such as skin and hair.


Chemistry

Nicotine is a
hygroscopic Hygroscopy is the phenomenon of attracting and holding water molecules via either absorption or adsorption from the surrounding environment, which is usually at normal or room temperature. If water molecules become suspended among the substan ...
, colorless to yellow-brown, oily liquid, that is readily soluble in alcohol, ether or light petroleum. It is miscible with
water Water (chemical formula ) is an Inorganic compound, inorganic, transparent, tasteless, odorless, and Color of water, nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living ...
in its neutral amine base form between 60 °C and 210 °C. It is a dibasic
nitrogenous base Nucleobases, also known as ''nitrogenous bases'' or often simply ''bases'', are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic b ...
, having Kb1=1×10−6, Kb2=1×10−11. It readily forms ammonium
salts In chemistry, a salt is a chemical compound consisting of an ionic assembly of positively charged cations and negatively charged anions, which results in a compound with no net electric charge. A common example is table salt, with positively c ...
with acids that are usually solid and water-soluble. Its flash point is 95 °C and its auto-ignition temperature is 244 °C. Nicotine is readily volatile (
vapor pressure Vapor pressure (or vapour pressure in English-speaking countries other than the US; see spelling differences) or equilibrium vapor pressure is defined as the pressure exerted by a vapor in thermodynamic equilibrium with its condensed phas ...
5.5 Pa at 25 °C) On exposure to ultraviolet light or various oxidizing agents, nicotine is converted to nicotine oxide, nicotinic acid (niacin, vitamin B3), and methylamine. Nicotine is
chiral Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is distinguishable from i ...
and hence optically active, having two enantiomeric forms. The naturally occurring form of nicotine is
levorotatory Optical rotation, also known as polarization rotation or circular birefringence, is the rotation of the orientation of the plane of polarization about the optical axis of linearly polarized light as it travels through certain materials. Circul ...
with a specific rotation of sub>D=–166.4° ((−)-nicotine). The
dextrorotatory Optical rotation, also known as polarization rotation or circular birefringence, is the rotation of the orientation of the plane of polarization about the optical axis of linearly polarized light as it travels through certain materials. Circul ...
form, (+)-nicotine is physiologically less active than (−)-nicotine. (−)-nicotine is more toxic than (+)-nicotine. The salts of (−)-nicotine are usually dextrorotatory; this conversion between levorotatory and dextrorotatory upon protonation is common among alkaloids. The hydrochloride and sulfate salts become optically inactive if heated in a closed vessel above 180 °C.
Anabasine Anabasine is a pyridine and piperidine alkaloid found in the Tree Tobacco ('' Nicotiana glauca'') plant, a close relative of the common tobacco plant (''Nicotiana tabacum''). It is a structural isomer of, and chemically similar to, nicotine. Its ...
is a structural isomer of nicotine, as both compounds have the
molecular formula In chemistry, a chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, ...
. Nicotine that is found in natural tobacco is primarily (99%) the S-enantiomer.  Conversely, the most common chemistry synthetic methods for generating nicotine yields a product that is approximately equal proportions of the S- and R-enantiomers. This suggests that tobacco-derived and synthetic nicotine can be determined by measuring the ratio of the two different enantiomers, although means exist for adjusting the relative levels of the enantiomers or performing a synthesis that only leads to the S-enantiomer. There is limited data on the relative physiological effects of these two enantiomers, especially in people. However, the studies to date indicate that (S)-nicotine is more potent than (R)-nicotine and (S)-nicotine causes stronger sensations or irritation than (R)-nicotine. To date, studies are not adequate to determine the relative addictiveness of the two enantiomers in people. Pod mod electronic cigarettes use nicotine in the form of a protonated nicotine, rather than free-base nicotine found in earlier generations.


Preparation

The first laboratory preparation of nicotine (as its
racemate In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...
) was described in 1904. : The starting material was an N-substituted pyrrole derivative, which was heated to convert it by a ,5sigmatropic shift to the isomer with a carbon bond between the pyrrole and pyridine rings, followed by methylation and selective reduction of the pyrrole ring using tin and hydrochloric acid. Many other syntheses of nicotine, in both racemic and chiral forms have since been published.


Biosynthesis

The biosynthetic pathway of nicotine involves a coupling reaction between the two cyclic structures that comprise nicotine. Metabolic studies show that the
pyridine Pyridine is a basic heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom. It is a highly flammable, weakly alkaline, water-miscible liquid with a ...
ring of nicotine is derived from
niacin Niacin, also known as nicotinic acid, is an organic compound and a form of vitamin B3, an essential human nutrient. It can be manufactured by plants and animals from the amino acid tryptophan. Niacin is obtained in the diet from a variet ...
(nicotinic acid) while the pyrrolidine is derived from ''N''-methyl-Δ1-pyrrollidium cation. Biosynthesis of the two component structures proceeds via two independent syntheses, the NAD pathway for niacin and the tropane pathway for ''N''-methyl-Δ1-pyrrollidium cation. The NAD pathway in the genus '' Nicotiana'' begins with the oxidation of aspartic acid into α-imino succinate by aspartate oxidase (AO). This is followed by a condensation with
glyceraldehyde-3-phosphate Glyceraldehyde 3-phosphate, also known as triose phosphate or 3-phosphoglyceraldehyde and abbreviated as G3P, GA3P, GADP, GAP, TP, GALP or PGAL, is a metabolite that occurs as an intermediate in several central pathways of all organisms.Nelson, ...
and a cyclization catalyzed by quinolinate synthase (QS) to give
quinolinic acid Quinolinic acid (abbreviated QUIN or QA), also known as pyridine-2,3-dicarboxylic acid, is a dicarboxylic acid with a pyridine backbone. It is a colorless solid. It is the biosynthetic precursor to niacin. Quinolinic acid is a downstream produc ...
. Quinolinic acid then reacts with phosphoriboxyl pyrophosphate catalyzed by quinolinic acid phosphoribosyl transferase (QPT) to form niacin mononucleotide (NaMN). The reaction now proceeds via the NAD salvage cycle to produce niacin via the conversion of
nicotinamide Niacinamide or Nicotinamide (NAM) is a form of vitamin B3 found in food and used as a dietary supplement and medication. As a supplement, it is used by mouth to prevent and treat pellagra (niacin deficiency). While nicotinic acid (niacin) may ...
by the enzyme nicotinamidase. The ''N''-methyl-Δ1-pyrrollidium cation used in the synthesis of nicotine is an intermediate in the synthesis of tropane-derived alkaloids. Biosynthesis begins with decarboxylation of
ornithine Ornithine is a non-proteinogenic amino acid that plays a role in the urea cycle. Ornithine is abnormally accumulated in the body in ornithine transcarbamylase deficiency. The radical is ornithyl. Role in urea cycle L-Ornithine is one of the produ ...
by
ornithine decarboxylase The enzyme ornithine decarboxylase (, ODC) catalyzes the decarboxylation of ornithine (a product of the urea cycle) to form putrescine. This reaction is the committed step in polyamine synthesis. In humans, this protein has 461 amino acids a ...
(ODC) to produce
putrescine Putrescine is an organic compound with the formula (CH2)4(NH2)2. It is a colorless solid that melts near room temperature. It is classified as a diamine. Together with cadaverine, it is largely responsible for the foul odor of putrefying flesh, ...
. Putrescine is then converted into ''N''-methyl putrescine via methylation by SAM catalyzed by putrescine ''N''-methyltransferase (PMT). ''N''-methylputrescine then undergoes
deamination Deamination is the removal of an amino group from a molecule. Enzymes that catalyse this reaction are called deaminases. In the human body, deamination takes place primarily in the liver, however it can also occur in the kidney. In situations of ...
into 4-methylaminobutanal by the ''N''-methylputrescine oxidase (MPO) enzyme, 4-methylaminobutanal then spontaneously cyclize into ''N''-methyl-Δ1-pyrrollidium cation. The final step in the synthesis of nicotine is the coupling between ''N''-methyl-Δ1-pyrrollidium cation and niacin. Although studies conclude some form of coupling between the two component structures, the definite process and mechanism remains undetermined. The current agreed theory involves the conversion of niacin into 2,5-dihydropyridine through 3,6-dihydronicotinic acid. The 2,5-dihydropyridine intermediate would then react with ''N''-methyl-Δ1-pyrrollidium cation to form enantiomerically pure (−)-nicotine.


Detection in body fluids

Nicotine can be quantified in blood, plasma, or urine to confirm a diagnosis of poisoning or to facilitate a medicolegal death investigation. Urinary or salivary cotinine concentrations are frequently measured for the purposes of pre-employment and health insurance medical screening programs. Careful interpretation of results is important, since passive exposure to cigarette smoke can result in significant accumulation of nicotine, followed by the appearance of its metabolites in various body fluids. Nicotine use is not regulated in competitive sports programs.


Methods for analysis of enantiomers

Methods for measuring the two enantiomers are straightforward and include normal-phase liquid chromatography, liquid chromatography with a chiral column. However, since methods can be used to alter the two enantiomers, it may not be possible to distinguish tobacco-derived from synthetic nicotine simply by measuring the levels of the two enantiomers. A new approach uses hydrogen and deuterium nuclear magnetic resonance to distinguish tobacco-derived and synthetic nicotine based on differences the substrates used in the natural synthetic pathway performed in the tobacco plant and the substrates most used in synthesis. Another approach measures the carbon-14 content which also differs between natural and laboratory-based tobacco. These methods remain to be fully evaluated and validated using a wide range of samples.


Natural occurrence

Nicotine is a
secondary metabolite Secondary metabolites, also called specialised metabolites, toxins, secondary products, or natural products, are organic compounds produced by any lifeform, e.g. bacteria, fungi, animals, or plants, which are not directly involved in the norma ...
produced in a variety of plants in the family Solanaceae, most notably in tobacco ''
Nicotiana tabacum ''Nicotiana tabacum'', or cultivated tobacco, is an Annual plant, annually grown herbaceous plant of the ''Nicotiana'' genus. The plant is tropical in origin, is commonly grown throughout the world, and is often found in Cultivation of tobacco, ...
'', where it can be found at high concentrations of 0.5 to 7.5%. Nicotine is also found in the leaves of other tobacco species, such as ''
Nicotiana rustica ''Nicotiana rustica'', commonly known as Aztec tobacco or strong tobacco, is a rainforest plant in the family Solanaceae. It is a very potent variety of tobacco, containing up to nine times more nicotine than common species of ''Nicotiana'' such ...
'' (in amounts of 2–14%). Nicotine production is strongly induced in response to wounding as part of a
jasmonate Jasmonate (JA) and its derivatives are lipid-based plant hormones that regulate a wide range of processes in plants, ranging from growth and photosynthesis to reproductive development. In particular, JAs are critical for plant defense against herb ...
-dependent reaction. Specialist insects on tobacco, such as the tobacco hornworm (''
Manduca sexta ''Manduca sexta'' is a moth of the family Sphingidae present through much of the Americas. The species was first described by Carl Linnaeus in his 1763 ''Centuria Insectorum''. Commonly known as the Carolina sphinx moth and the tobacco hawk mo ...
''), have a number of adaptations to the detoxification and even adaptive re-purposing of nicotine. Nicotine is also found at low concentrations in the nectar of tobacco plants, where it may promote
outcrossing Out-crossing or out-breeding is the technique of crossing between different breeds. This is the practice of introducing distantly related genetic material into a breeding line, thereby increasing genetic diversity. Outcrossing can be a usefu ...
by affecting the behavior of hummingbird pollinators. Nicotine occurs in smaller amounts (varying from 2–7  μg/ kg, or 20–70 millionths of a percent wet weight) in other Solanaceaeous plants, including some crop species such as
potato The potato is a starchy food, a tuber of the plant ''Solanum tuberosum'' and is a root vegetable native to the Americas. The plant is a perennial in the nightshade family Solanaceae. Wild potato species can be found from the southern Unit ...
es,
tomato The tomato is the edible berry of the plant ''Solanum lycopersicum'', commonly known as the tomato plant. The species originated in western South America, Mexico, and Central America. The Mexican Nahuatl word gave rise to the Spanish word ...
es, eggplant, and
peppers Pepper or peppers may refer to: Food and spice * Piperaceae or the pepper family, a large family of flowering plant ** Black pepper * ''Capsicum'' or pepper, a genus of flowering plants in the nightshade family Solanaceae ** Bell pepper ** Chili ...
, as well as non-crop species such as ''
Duboisia hopwoodii ''Duboisia hopwoodii'' is a shrub native to the arid interior region of Australia. Common names include pituri, pitchuri thornapple or pitcheri. Description The species has an erect habit, usually growing to between 1 and 3 metres in height, wit ...
''. The amounts of nicotine in tomatoes lowers substantially as the fruit ripens. A 1999 report found "In some papers it is suggested that the contribution of dietary nicotine intake is significant when compared with exposure to ETS nvironmental tobacco smokeor by active smoking of small numbers of cigarettes. Others consider the dietary intake to be negligible unless inordinately large amounts of specific vegetables are consumed." The amount of nicotine eaten per day is roughly around 1.4 and 2.25  μg/day at the 95th percentile. These numbers may be low due to insufficient food intake data. The concentrations of nicotine in vegetables are difficult to measure accurately, since they are very low (parts per billion range).


History, society and culture

Nicotine was originally isolated from the tobacco plant in 1828 by chemists Wilhelm Heinrich Posselt and Karl Ludwig Reimann from
Germany Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated betwe ...
, who believed it was a poison. Its chemical
empirical formula In chemistry, the empirical formula of a chemical compound is the simplest whole number ratio of atoms present in a compound. A simple example of this concept is that the empirical formula of sulfur monoxide, or SO, would simply be SO, as is the ...
was described by Melsens in 1843, its structure was discovered by
Adolf Pinner Adolf Pinner (August 31, 1842 – May 21, 1909) was a German chemist. Early life and education He was educated at the Jewish Theological Seminary of Breslau, Jewish Theological Seminary at Breslau and at the University of Berlin (Phd in Chemis ...
and Richard Wolffenstein in 1893, and it was first synthesized by Amé Pictet and A. Rotschy in 1904. Nicotine is named after the tobacco plant ''
Nicotiana tabacum ''Nicotiana tabacum'', or cultivated tobacco, is an Annual plant, annually grown herbaceous plant of the ''Nicotiana'' genus. The plant is tropical in origin, is commonly grown throughout the world, and is often found in Cultivation of tobacco, ...
,'' which in turn is named after the French ambassador in
Portugal Portugal, officially the Portuguese Republic ( pt, República Portuguesa, links=yes ), is a country whose mainland is located on the Iberian Peninsula of Southwestern Europe, and whose territory also includes the Atlantic archipelagos of ...
, Jean Nicot de Villemain, who sent tobacco and seeds to
Paris Paris () is the Capital city, capital and List of communes in France with over 20,000 inhabitants, most populous city of France, with an estimated population of 2,165,423 residents in 2019 in an area of more than 105 km² (41 sq mi), ma ...
in 1560, presented to the French King, and who promoted their medicinal use. Smoking was believed to protect against illness, particularly the plague.
Tobacco Tobacco is the common name of several plants in the genus '' Nicotiana'' of the family Solanaceae, and the general term for any product prepared from the cured leaves of these plants. More than 70 species of tobacco are known, but the ...
was introduced to
Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a subcontinent of Eurasia and it is located entirel ...
in 1559, and by the late 17th century, it was used not only for smoking but also as an insecticide. After
World War II World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposing ...
, over 2,500 tons of nicotine insecticide were used worldwide, but by the 1980s the use of nicotine insecticide had declined below 200 tons. This was due to the availability of other insecticides that are cheaper and less harmful to mammals. The nicotine content of popular American-brand cigarettes has increased over time, and one study found that there was an average increase of 1.78% per year between the years of 1998 and 2005. Although methods of production of synthetic nicotine have existed for decades, it was believed that the cost of making nicotine by laboratory synthesis was cost prohibitive compared to extracting nicotine from tobacco. However, recently synthetic nicotine started to be found in different brands of e-cigarettes and oral pouches and marketed as “tobacco-free.” The US FDA is tasked with reviewing tobacco products such as e-cigarettes and determining which can be authorized for sale.  In response to the likelihood that FDA would not authorize many e-cigarettes to be marketed, e-cigarette companies began marketing products that they claimed to contain nicotine that were not made or derived from tobacco, but contained synthetic nicotine instead, and thus, would be outside FDA’s tobacco regulatory authority. Similarly, nicotine pouches that claimed to contain non-tobacco (synthetic) nicotine were also introduced. The cost of synthetic nicotine has decreased as the market for the product increased. In March 2022, the U.S. Congress passed a law (the
Consolidated Appropriations Act, 2022 Consolidated Appropriations Act, 2022 is a $1.5 trillion omnibus spending bill. The bill was passed by Congress on March 14, 2022. The bill was signed into law by President Joe Biden on March 15, 2022. The law includes $13.6 billion in aid to ...
) that expanded FDA’s tobacco regulatory authority to include tobacco products containing nicotine from any source, thereby including products made with synthetic nicotine. ----


Legal status

In the United States, nicotine products and Nicotine Replacement Therapy products like Nicotrol are only available to persons 21 and above; proof of age is required; not for sale in vending machine or from any source where proof of age cannot be verified. As of 2019, the minimum age to use tobacco in the US is 21 at the federal level. In the European Union, the minimum age to purchase nicotine products is 18. However, there is no minimum age requirement to use tobacco or nicotine products.


In media

In some anti-smoking literature, the harm that tobacco smoking and nicotine addiction does is personified as Nick O'Teen, represented as a humanoid with some aspect of a cigarette or cigarette butt about him or his clothes and hat. Nick O'Teen was a villain that was created for the
Health Education Council Health, according to the World Health Organization, is "a state of complete physical, Mental health, mental and social well-being and not merely the absence of disease and infirmity".World Health Organization. (2006)''Constitution of the World H ...
. Nicotine was often compared to caffeine in advertisements in the 1980s by the tobacco industry, and later in the 2010s by the electronic cigarettes industry, in an effort to reduce the stigmatization and the public perception of the risks associated with nicotine use.


Research


Central nervous system

While acute/initial nicotine intake causes activation of neuronal nicotine receptors, chronic low doses of nicotine use leads to desensitization of those receptors (due to the development of tolerance) and results in an antidepressant effect, with early research showing low dose nicotine patches could be an effective treatment of
major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...
in non-smokers. Though tobacco smoking is associated with an increased risk of Alzheimer's disease, there is evidence that nicotine itself has the potential to prevent and treat Alzheimer's disease. Smoking is associated with a decreased risk of Parkinson's Disease; however, it is unknown whether this is due to people with healthier brain dopaminergic reward centers (the area of the brain affected by Parkinson's) being more likely to enjoy smoking and thus pick up the habit, nicotine directly acting as a neuroprotective agent, or other compounds in cigarette smoke acting as neuroprotective agents.


Immune system

Immune cells of both the Innate immune system and
adaptive immune system The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...
s frequently express the α2, α5, α6, α7, α9, and α10 subunits of nicotinic acetylcholine receptors. Evidence suggests that nicotinic receptors which contain these subunits are involved in the regulation of immune function.


Optopharmacology

A photoactivatable form of nicotine, which releases nicotine when exposed to
ultraviolet light Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nanometer, nm (with a corresponding frequency around 30 Hertz, PHz) to 400 nm (750 Hertz, THz), shorter than that of visible light, but longer than ...
with certain conditions, has been developed for studying nicotinic acetylcholine receptors in brain tissue.


Oral health

Several ''in vitro'' studies have investigated the potential effects of nicotine on a range of oral cells. A recent systematic review concluded that nicotine was unlikely to be cytotoxic to oral cells ''in vitro'' in most physiological conditions but further research is needed. Understanding the potential role of nicotine in oral health has become increasingly important given the recent introduction of novel nicotine products and their potential role in helping smokers quit.


See also

* 6-Chloronicotine *
Nicotine marketing Nicotine marketing is the marketing of nicotine-containing products or use. Traditionally, the tobacco industry markets cigarette smoking, but it is increasingly marketing other products, such as electronic cigarettes and heated tobacco produ ...


References


External links


Toxicology monograph for Nicotine
from the
Hazardous Substances Data Bank The Hazardous Substances Data Bank (HSDB) is a toxicology database on the United States, U.S. National Library of Medicine's (NLM) Toxicology Data Network (TOXNET). It focuses on the toxicology of potentially hazardous chemicals, and includes inf ...

Chemical Hazards monograph for Nicotine
from the
National Institute for Occupational Safety and Health The National Institute for Occupational Safety and Health (NIOSH, ) is the United States federal agency responsible for conducting research and making recommendations for the prevention of work-related injury and illness. NIOSH is part of the C ...

Laboratory Chemical Safety Summary for Nicotine
from
PubChem PubChem is a database of chemical molecules and their activities against biological assays. The system is maintained by the National Center for Biotechnology Information (NCBI), a component of the National Library of Medicine, which is part of ...
{{Authority control Alkaloids found in Erythroxylum coca Alkaloids found in Nicotiana Anorectics Pfizer brands GSK plc brands Anxiolytics Euphoriants Nicotinic agonists Nicotinic antagonists Plant toxin insecticides Pregnane X receptor agonists Pyridine alkaloids Pyrrolidine alkaloids Smoking Stimulants Teratogens 3-Pyridyl compounds