|Systematic (IUPAC) name|
|Trade names||Nicorette, Nicotrol|
|Pregnancy cat.||D (AU) D (US)|
|Legal status||Pharmacy Only (S2) (AU) GSL (UK) OTC (US)|
|Routes||Inhalation; Insufflation; Oral – Buccal, Sublingual, and Ingestion; Transdermal; Rectal,|
|Bioavailability||20 to 45% (oral), 53% (intranasal), 68% (transdermal)|
|Half-life||1-2 hours; 20 hours active metabolite (cotinine)|
|Excretion||Urine (10-20% (gum), pH-dependent; 30% (inhaled); 10-30% (intranasal))|
|ATC code||N07 QP53|
|PDB ligand ID||NCT (, )|
|Mol. mass||162.23 g/mol|
|Melt. point||-79 °C (-110 °F)|
|Boiling point||247 °C (477 °F)|
|14px (what is this?)|
Nicotine is a potent parasympathomimetic alkaloid found in the nightshade family of plants (Solanaceae) and a stimulant drug. It is a nicotinic acetylcholine receptor agonist. It is made in the roots and accumulates in the leaves of the plants. It constitutes approximately 0.6–3.0% of the dry weight of tobacco and is present in the range of 2–7 µg/kg of various edible plants. It functions as an antiherbivore chemical; consequently, nicotine was widely used as an insecticide in the past and nicotine analogs such as imidacloprid are currently widely used.
In lesser doses (an average cigarette yields about 1 mg of absorbed nicotine), the substance acts as a stimulant in mammals, while high amounts (50–100 mg) can be harmful. This stimulant effect is likely to be a major contributing factor to the dependence-forming properties of tobacco smoking. The nicotine content of popular American-brand cigarettes has slowly increased over the years, and one study found that there was an average increase of 1.78% per year between the years of 1998 and 2005.
- 1 History and name
- 2 Chemistry
- 3 Biosynthesis
- 4 Pharmacology
- 5 Toxicology
- 6 Detection of use
- 7 Medical uses
- 8 Health effects
- 9 Use as an insecticide
- 10 Synthesis & Analogs
- 11 See also
- 12 References
- 13 Further reading
- 14 External links
History and name
Nicotine is named after the tobacco plant Nicotiana tabacum, which in turn is named after the French ambassador in Portugal, Jean Nicot de Villemain, who sent tobacco and seeds to Paris in 1560, and who promoted their medicinal use. The tobacco and its seeds were brought to Ambassador Nicot from Brazil by Luis de Gois, a Portuguese colonist in São Paulo.
Nicotine was first isolated from the tobacco plant in 1828 by physician Wilhelm Heinrich Posselt and chemist Karl Ludwig Reimann of Germany, who considered it a poison. Its chemical empirical formula was described by Melsens in 1843, its structure was discovered by Adolf Pinner and Richard Wolffenstein in 1893,[clarification needed] and it was first synthesized by Amé Pictet and A. Rotschy in 1904.
Nicotine is a hygroscopic, colorless oily liquid that is readily soluble in alcohol, ether or light petroleum. It is miscible with water in its base form between 60°C and 210°C. As a nitrogenous base, nicotine forms salts 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 optically active, having two enantiomeric forms. The naturally occurring form of nicotine is levorotatory with a specific rotation of [α]D = –166.4° ((−)-nicotine). The dextrorotatory form, (+)-nicotine is physiologically less active than (–)-nicotine. (−)-nicotine is more toxic than (+)-nicotine. The salts of (+)-nicotine are usually dextrorotatory. The hydrochloride and sulphate salts become optically inactive if heated in a closed vessel above 180°C.
On exposure to ultraviolet light or various oxidizing agents, nicotine is converted to nicotine oxide, nicotinic acid (vitamin B3), and methylamine.
The biosynthetic pathway of nicotine involves a coupling reaction between the two cyclic structures that compose nicotine. Metabolic studies show that the pyridine ring of nicotine is derived from niacin (nicotinic acid) while the pyrrolidone 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 and a cyclization catalyzed by quinolinate synthase (QS) to give quinolinic acid. 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 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 by ornithine decarboxylase (ODC) to produce putrescine. Putrescine is then converted into N-methyl putrescine via methylation by SAM catalyzed by putrescine N-methyltransferase (PMT). N-methylputrescine then undergoes deamination 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.
As nicotine enters the body, it is distributed quickly through the bloodstream and crosses the blood–brain barrier reaching the brain within 10–20 seconds after inhalation. The elimination half-life of nicotine in the body is around two hours.
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 acts on nicotinic acetylcholine receptors, specifically the α3β4 ganglion type nicotinic receptor, present in the autonomic ganglia and adrenal medulla, and a central nervous system (CNS) α4β2 nicotinic receptor. In small concentrations, nicotine increases the activity of these cholinergic receptors and indirectly on a variety of other neurotransmitters such as dopamine.
Nicotine is metabolized in the liver by cytochrome P450 enzymes (mostly CYP2A6, and also by CYP2B6). 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.
In the central nervous system
By binding to nicotinic acetylcholine receptors, nicotine increases the levels of several neurotransmitters – acting as a sort of "volume control". It is thought that increased levels of dopamine in the reward circuits of the brain are a major contributor to the apparent euphoria and relaxation, and addiction caused by nicotine consumption. This release of dopamine induced by nicotine is thought to occur via a cholinergic–dopaminergic link, mediated by a neuropeptide, ghrelin, in the ventral tegmentum. Nicotine has a higher affinity for acetylcholine 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.
Tobacco smoke contains anabasine, anatabine, and nornicotine. It also contains the monoamine oxidase inhibitors harman and norharman. These beta-carboline compounds significantly decrease MAO activity in smokers. MAO enzymes break down monoaminergic neurotransmitters such as dopamine, norepinephrine, and serotonin. It is thought that the powerful interaction between the MAOIs and the nicotine is responsible for most of the addictive properties of tobacco smoking. The addition of five minor tobacco alkaloids increases nicotine-induced hyperactivity, sensitization and intravenous self-administration in rats.
Chronic nicotine exposure via tobacco smoking up-regulates alpha4beta2* nAChR in cerebellum and brainstem regions but not habenulopeduncular structures. Alpha4beta2 and alpha6beta2 receptors, present in the ventral tegmental area, play a crucial role in mediating the reinforcement effects of nicotine.
Research published in 2011 found that nicotine inhibits class I and II histone deacetylases, chromatin-modifying enzymes involved in epigenetics. This inhibition has been shown to increase susceptibility to cocaine addiction in rodents.
In the sympathetic nervous system
Nicotine also activates the sympathetic nervous system, acting via splanchnic nerves to the adrenal medulla, stimulates the release of epinephrine. Acetylcholine released by preganglionic sympathetic fibers of these nerves acts on nicotinic acetylcholine receptors, causing the release of epinephrine (and noradrenaline) into the bloodstream. Nicotine also has an affinity for melanin-containing tissues due to its precursor function in melanin synthesis or due to the irreversible binding of melanin and nicotine. This has been suggested to underlie the increased nicotine dependence and lower smoking cessation rates in darker pigmented individuals. However, further research is warranted before a definite conclusive link can be inferred.
In adrenal medulla
By binding to ganglion type nicotinic receptors in the adrenal medulla nicotine increases flow of adrenaline (epinephrine), a stimulating hormone and neurotransmitter. By binding to the receptors, it causes cell depolarization and an influx of calcium through voltage-gated calcium channels. Calcium triggers the exocytosis of chromaffin granules and thus the release of epinephrine (and norepinephrine) into the bloodstream. The release of epinephrine (adrenaline) causes an increase in heart rate, blood pressure and respiration, as well as higher blood glucose levels.
Nicotine is the natural product of tobacco, having a half-life of 1 to 2 hours. Cotinine is an active metabolite of nicotine that remains in the blood for 18 to 20 hours, making it easier to analyze due to its longer half-life.
| NFPA 704|
The LD50 of nicotine is 50 mg/kg for rats and 3 mg/kg for mice. 30–60 mg (0.5–1.0 mg/kg) can be a lethal dosage for adult humans. However the widely used human LD50 estimate of 0.5–1.0 mg/kg was questioned in a 2013 review, in light of several documented cases of humans surviving much higher doses; the 2013 review suggests that the lower limit causing fatal outcomes is 500–1000 mg of ingested nicotine, corresponding to 6.5–13 mg/kg orally. Nevertheless nicotine has a relatively high toxicity in comparison to many other alkaloids such as caffeine, which has an LD50of 127 mg/kg when administered to mice.
It is unlikely that a person would overdose on nicotine through smoking alone, the US Food and Drug Administration (FDA) states in 2013 "There are no significant safety concerns associated with using more than one OTC NRT at the same time, or using an OTC NRT at the same time as another nicotine-containing product—including a cigarette." Spilling a high concentration of nicotine onto the skin can cause intoxication or even death, since nicotine readily passes into the bloodstream following dermal contact.
Historically, nicotine has not been regarded as a carcinogen. The IARC has not evaluated nicotine in its standalone form or assigned it to an official carcinogen group. While no epidemiological evidence supports that nicotine alone acts as a carcinogen in the formation of human cancer, research over the last decade has identified nicotine's carcinogenic potential in animal models and cell culture. Indirectly, nicotine increases cholinergic signalling (and adrenergic signalling in the case of colon cancer), thereby impeding apoptosis (programmed cell death), promoting tumor growth, and activating growth factors and cellular mitogenic factors such as 5-LOX, and EGF. Nicotine also promotes cancer growth by stimulating angiogenesis and neovascularization. In one study, nicotine administered to mice with tumors caused increases in tumor size (twofold increase), metastasis (nine-fold increase), and tumor recurrence (threefold increase). N-Nitrosonornicotine (NNN), classified by the IARC as a Group 1 carcinogen, is produced endogenously from nitrite in saliva and nicotine.
In pregnancy, a 2013 review noted that "nicotine is only 1 of more than 4000 compounds to which the fetus is exposed through maternal smoking. Of these, ∼30 compounds have been associated with adverse health outcomes. Although the exact mechanisms by which nicotine produces adverse fetal effects are unknown, it is likely that hypoxia, undernourishment of the fetus, and direct vasoconstrictor effects on the placental and umbilical vessels all play a role. Nicotine also has been shown to have significant deleterious effects on brain development, including alterations in brain metabolism and neurotransmitter systems and abnormal brain development." It also notes that "abnormalities of newborn neurobehavior, including impaired orientation and autonomic regulation and abnormalities of muscle tone, have been identified in a number of prenatal nicotine exposure studies" and that there is weak data associating fetal nicotine exposure with newborn facial clefts, and that there is no good evidence for newborns suffering nicotine withdrawal from fetal exposure to nicotine.
Effective April 1, 1990, the Office of Environmental Health Hazard Assessment (OEHHA) of the California Environmental Protection Agency added nicotine to the list of chemicals known to cause developmental toxicity.
Nicotine increases blood pressure and heart rate. Nicotine can also induce potentially atherogenic genes in human coronary artery endothelial cells. Microvascular injury can result through its action on nicotinic acetylcholine receptors (nAChRs).
A study on rats showed that nicotine exposure abolishes the beneficial and protective effects of estrogen on the hippocampus, an estrogen-sensitive region of the brain involved in memory formation and retention.
Dependence and withdrawal
Nicotine is addictive. It activates the mesolimbic pathway ("reward system") – the circuitry within the brain that regulates feelings of pleasure and euphoria. Dopamine is one of the key neurotransmitters actively involved in the brain. Nicotine may be as addictive as heroin, cocaine, or alcohol. Like other physically addictive drugs, nicotine withdrawal causes downregulation of the production of dopamine and other stimulatory neurotransmitters as the brain attempts to compensate for artificial stimulation. As dopamine is downregulated, the sensitivity of nicotinic acetylcholine receptors decreases. To compensate for this compensatory mechanism, the brain in turn upregulates the number of receptors, convoluting its regulatory effects with compensatory mechanisms meant to counteract other compensatory mechanisms. An example is the increase in norepinephrine, one of the successors to dopamine, which inhibit reuptake of the glutamate receptors, in charge of memory and cognition. The net effect is an increase in reward pathway sensitivity, the opposite of other addictive drugs such as cocaine and heroin, which reduce reward pathway sensitivity. This alteration in neuronal chemistry can persist for months following the last administration.
Prevention by vaccines
Because of the severe addictions and the harmful effects of smoking, vaccination protocols have been developed. The principle operates under the premise that if an antibody is attached to a nicotine molecule, it will be prevented from diffusing through the capillaries, thus making it less likely that it ever affects the brain by binding to nicotinic acetylcholine receptors.
These include attaching the nicotine molecule as a hapten to a protein carrier such as keyhole limpet hemocyanin or a safe modified bacterial toxin to elicit an active immune response. Often it is added with bovine serum albumin.
Additionally, because of concerns with the unique immune systems of individuals being liable to produce antibodies against endogenous hormones and over-the-counter drugs, monoclonal antibodies have been developed for short term passive immune protection. They have half-lives varying from hours to weeks. Their half-lives depend on their ability to resist degradation from pinocytosis by epithelial cells.
Detection of use
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.
Although population level effectiveness has not been demonstrated, the primary therapeutic use of nicotine is in treating nicotine dependence in order to eliminate smoking with the damage it does to health. Controlled levels of nicotine are given to patients through gums, dermal patches, lozenges, electronic/substitute cigarettes or nasal sprays in an effort to wean them off their dependence.
However, in a few situations, smoking has been observed to be of therapeutic value. These are often referred to as "Smoker’s Paradoxes". Although in most cases the actual mechanism is understood only poorly or not at all, it is generally believed that the principal beneficial action is due to the nicotine administered, and that administration of nicotine without smoking may be as beneficial as smoking, without the higher risk to health due to tar and other substances found in tobacco.
For instance, studies suggest that smokers require less frequent repeated revascularization after percutaneous coronary intervention(PCI). Risk of ulcerative colitis has been frequently shown to be reduced in smokers on a dose-dependent basis; the effect is eliminated if the individual stops smoking. Smoking also appears to interfere with development of Kaposi's sarcoma in patients with HIV.
Nicotine reduces the chance of preeclampsia, and atopic disorders such as allergic asthma.[dubious ] A plausible mechanism of action in these cases may be nicotine acting as an anti-inflammatory agent, and interfering with the inflammation-related disease process, as nicotine has vasoconstrictive effects. An obvious bias to this study is selection bias as persons with more severe asthma are less likely to adopt a habit of smoking due to exacerbation of their condition in response to exposure.
While 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. Nicotine has been shown to delay the onset of Parkinson's disease in studies involving monkeys and humans. A study has shown a protective effect of nicotine itself on neurons due to nicotine activation of α7-nAChR and the PI3K/Akt pathway which inhibits apoptosis-inducing factor release and mitochondrial translocation, cytochrome c release and caspase 3 activation.
Studies have indicated that nicotine can be used to help adults suffering from autosomal dominant nocturnal frontal lobe epilepsy. The same areas that cause seizures in that form of epilepsy are responsible for processing nicotine in the brain.
Studies suggest a correlation between smoking and schizophrenia, with estimates near 75% for the proportion of schizophrenic patients who smoke. Although the nature of this association remains unclear, it has been argued that the increased level of smoking in schizophrenia may be due to a desire to self-medicate with nicotine. Other research found that mildly dependent users got some benefit from nicotine, but not those who were highly dependent.
People with ADHD smoke cigarettes at rates significantly higher than others, and start smoking earlier, smoke more, and have more difficulty quitting. Research is ongoing to understand if the brain conditions underlying ADHD make people more prone to nicotine addiction, if the nicotine has some therapeutic value, or if there is no causation underlying the correlation.
While acute/initial nicotine intake causes activation of nicotine receptors, chronic low doses of nicotine use leads to desensitisation of nicotine receptors (due to the development of tolerance) and results in an antidepressant effect, with research showing low dose nicotine patches being an effective treatment of major depressive disorder in non-smokers.
Nicotine (in the form of chewing gum or a transdermal patch) has been explored as an experimental treatment for OCD. Small studies show some success, even in otherwise treatment-refractory cases.
The relationship between smoking and inflammatory bowel disease has been firmly established, but remains a source of confusion among both patients and doctors. It is negatively associated with ulcerative colitis but positively associated with Crohn's disease. In addition, it has opposite influences on the clinical course of the two conditions with benefit in ulcerative colitis but a detrimental effect in Crohn's disease.
Nicotine's mood-altering effects are different by report: in particular it is both a stimulant and a relaxant. First causing a release of glucose from the liver and epinephrine (adrenaline) from the adrenal medulla, it causes stimulation. Users report feelings of relaxation, sharpness, calmness, and alertness. Like any stimulant, it may very rarely cause the often uncomfortable neuropsychiatric effect of akathisia. By reducing the appetite and raising the metabolism, some smokers may lose weight as a consequence.
When a cigarette is smoked, nicotine-rich blood passes from the lungs to the brain within seven seconds and immediately stimulates the release of many chemical messengers such as acetylcholine, norepinephrine, epinephrine, arginine vasopressin, serotonin, dopamine, and beta-endorphin.  This release of neurotransmitters and hormones is responsible for most of nicotine's psychoactive effects. Nicotine appears to enhance concentration and memory due to the increase of acetylcholine. It also appears to enhance alertness due to the increases of acetylcholine and norepinephrine. Arousal is increased by the increase of norepinephrine. Pain is reduced by the increases of acetylcholine and beta-endorphin. Anxiety is reduced by the increase of beta-endorphin. Nicotine also extends the duration of positive effects of dopamine and increases sensitivity in brain reward systems. Most cigarettes (in the smoke inhaled) contain 1 to 3 milligrams of nicotine.
Research suggests that, when smokers wish to achieve a stimulating effect, they take short quick puffs, which produce a low level of blood nicotine. This stimulates nerve transmission. When they wish to relax, they take deep puffs, which produce a high level of blood nicotine, which depresses the passage of nerve impulses, producing a mild sedative effect. At low doses, nicotine potently enhances the actions of norepinephrine and dopamine in the brain, causing a drug effect typical of those of psychostimulants. At higher doses, nicotine enhances the effect of serotonin and opiate activity, producing a calming, pain-killing effect. Nicotine is unique in comparison to most drugs, as its profile changes from stimulant to sedative/pain killer in increasing dosages and use, a phenomenon described by Paul Nesbitt in his doctoral dissertation and subsequently referred to as "Nesbitt's Paradox".
Use as an insecticide
Tobacco was introduced to Europe in 1559, and by the late 17th century, it was used not only for smoking but also as an insecticide. After World War II, over 2,500 tons of nicotine insecticide (waste from the tobacco industry) 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.
In 2008, the EPA received a request, from the registrant, to cancel the registration of the last nicotine pesticide registered in the United States. This request was granted, and since 1 January 2014, this pesticide has not been available for sale.
Synthesis & Analogs
- Nicotiana rustica
- Nicotiana tabacum
- Substance dependence
- Tobacco products
- Puke weed
- "Smoking and Tobacco Control Monograph No. 9" (PDF). Retrieved 2012-12-19.
- "Determination of the Nicotine Content of Various Edible Nightshades (Solanaceae) and Their Products and Estimation of the Associated Dietary Nicotine Intake". Retrieved 2008-10-05.
- Rodgman, Alan; Perfetti, Thomas A. (2009). The chemical components of tobacco and tobacco smoke. Boca Raton, FL: CRC Press. ISBN 1-4200-7883-6. LCCN 2008018913.[page needed]
- Ujváry, István (1999). "Nicotine and Other Insecticidal Alkaloids". In Yamamoto, Izuru; Casida, John. Nicotinoid Insecticides and the Nicotinic Acetylcholine Receptor. Tokyo: Springer-Verlag. pp. 29–69.
- "Nicotine (PIM)". Inchem.org. Retrieved 2012-12-19.
- Genetic Science Learning Center. "How Drugs Can Kill".
- Mayer B (October 2013). "How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century". Arch. Toxicol. 88 (1): 5–7. PMID 24091634. doi:10.1007/s00204-013-1127-0.
- Connolly, G. N; Alpert, H. R; Wayne, G. F; Koh, H (2007). "Trends in nicotine yield in smoke and its relationship with design characteristics among popular US cigarette brands, 1997–2005". Tobacco Control 16 (5): e5. PMC 2598548. PMID 17897974. doi:10.1136/tc.2006.019695.
- Posselt, W.; Reimann, L. (1828). "Chemische Untersuchung des Tabaks und Darstellung eines eigenthümlich wirksamen Prinzips dieser Pflanze" [Chemical investigation of tobacco and preparation of a characteristically active constituent of this plant]. Magazin für Pharmacie (in German) 6 (24): 138–161.
- Henningfield JE, Zeller M (March 2006). "Nicotine psychopharmacology research contributions to United States and global tobacco regulation: a look back and a look forward". Psychopharmacology (Berl.) 184 (3–4): 286–91. PMID 16463054. doi:10.1007/s00213-006-0308-4.
- Melsens, Louis-Henri-Frédéric (1843) "Note sur la nicotine," Annales de chimie et de physique, third series, vol. 9, pages 465-479; see especially page 470. [Note: The empirical formula that Melsens provides is incorrect because at that time, chemists used the wrong atomic mass for carbon (6 instead of 12).]
- Pinner, A.; Wolffenstein, R. (1891). "Ueber Nicotin". Berichte der deutschen chemischen Gesellschaft 24: 1373. doi:10.1002/cber.189102401242.
- Pinner, A. (1893). "Ueber Nicotin. Die Constitution des Alkaloïds". Berichte der deutschen chemischen Gesellschaft 26: 292. doi:10.1002/cber.18930260165.
- Pinner, A. (1893). "Ueber Nicotin. I. Mitteilung". Archiv der Pharmazie 231 (5–6): 378. doi:10.1002/ardp.18932310508.
- Pictet, Amé; Rotschy, A. (1904). "Synthese des Nicotins". Berichte der deutschen chemischen Gesellschaft 37 (2): 1225. doi:10.1002/cber.19040370206.
- www.sciencelab.com/msds.php?msdsId=9926222 Material Safety Data Sheet L-Nicotine MSDS
- Gause, G. F. (1941). "Chapter V: Analysis of various biological processes by the study of the differential action of optical isomers". In Luyet, B. J. Optical Activity and Living Matter. A series of monographs on general physiology 2. Normandy, Missouri: Biodynamica.
- Lamberts, Burton L.; Dewey, Lovell J.; Byerrum, Richard U. (1959). "Ornithine as a precursor for the pyrrolidine ring of nicotine". Biochimica et Biophysica Acta 33 (1): 22–6. PMID 13651178. doi:10.1016/0006-3002(59)90492-5.
- Dawson, R. F.; Christman, D. R.; d'Adamo, A.; Solt, M. L.; Wolf, A. P. (1960). "The Biosynthesis of Nicotine from Isotopically Labeled Nicotinic Acids1". Journal of the American Chemical Society 82 (10): 2628. doi:10.1021/ja01495a059.
- Ashihara, Hiroshi; Crozier, Alan; Komamine, Atsushi (eds.). Plant metabolism and biotechnology. Cambridge: Wiley. ISBN 978-0-470-74703-2.[page needed]
- Le Houezec J (September 2003). "Role of nicotine pharmacokinetics in nicotine addiction and nicotine replacement therapy: a review". Int. J. Tuberc. Lung Dis. 7 (9): 811–9. PMID 12971663.
- Benowitz NL, Jacob P, Jones RT, Rosenberg J (May 1982). "Interindividual variability in the metabolism and cardiovascular effects of nicotine in man". J. Pharmacol. Exp. Ther. 221 (2): 368–72. PMID 7077531.
- Russell MA, Jarvis M, Iyer R, Feyerabend C. Relation of nicotine yield of cigarettes to blood nicotine concentrations in smokers. Br Med J. 1980 April 5; 280(6219): 972–976.
- Hukkanen J, Jacob P, Benowitz NL (March 2005). "Metabolism and disposition kinetics of nicotine". Pharmacol. Rev. 57 (1): 79–115. PMID 15734728. doi:10.1124/pr.57.1.3.
- "The danger of third-hand smoke". Chromatography Online 7 (3). 22 February 2011.
- Benowitz, N. L.; Herrera, B; Jacob p, 3rd (2004). "Mentholated Cigarette Smoking Inhibits Nicotine Metabolism". Journal of Pharmacology and Experimental Therapeutics 310 (3): 1208–15. PMID 15084646. doi:10.1124/jpet.104.066902.
- Dickson, Suzanne L.; Egecioglu, Emil; Landgren, Sara; Skibicka, Karolina P.; Engel, Jörgen A.; Jerlhag, Elisabet (2011). "The role of the central ghrelin system in reward from food and chemical drugs". Molecular and Cellular Endocrinology 340 (1): 80–7. PMID 21354264. doi:10.1016/j.mce.2011.02.017.
- Katzung, Bertram G. (2006). Basic and Clinical Pharmacology. New York: McGraw-Hill Medical. pp. 99–105.
- Xiu X, Puskar NL, Shanata JA, Lester HA, Dougherty DA (March 2009). "Nicotine binding to brain receptors requires a strong cation-pi interaction". Nature 458 (7237): 534–7. Bibcode:2009Natur.458..534X. PMC 2755585. PMID 19252481. doi:10.1038/nature07768.
- Herraiz T, Chaparro C (2005). "Human monoamine oxidase is inhibited by tobacco smoke: beta-carboline alkaloids act as potent and reversible inhibitors". Biochem. Biophys. Res. Commun. 326 (2): 378–86. PMID 15582589. doi:10.1016/j.bbrc.2004.11.033.
- Fowler JS, Volkow ND, Wang GJ, et al. (1998). "Neuropharmacological actions of cigarette smoke: brain monoamine oxidase B (MAO B) inhibition". J Addict Dis 17 (1): 23–34. PMID 9549600. doi:10.1300/J069v17n01_03.
- Villégier AS, Blanc G, Glowinski J, Tassin JP (September 2003). "Transient behavioral sensitization to nicotine becomes long-lasting with monoamine oxidases inhibitors". Pharmacol. Biochem. Behav. 76 (2): 267–74. PMID 14592678. doi:10.1016/S0091-3057(03)00223-5.
- Villégier AS, Salomon L, Granon S, Changeux JP, Belluzzi JD, Leslie FM, Tassin JP (August 2006). "Monoamine oxidase inhibitors allow locomotor and rewarding responses to nicotine". Neuropsychopharmacology 31 (8): 1704–13. PMID 16395299. doi:10.1038/sj.npp.1300987.
- Wüllner U, Gündisch D, Herzog H, Minnerop M, Joe A, Warnecke M, Jessen F, Schütz C, Reinhardt M, Eschner W, Klockgether T, Schmaljohann J (January 2008). "Smoking upregulates alpha4beta2* nicotinic acetylcholine receptors in the human brain". Neurosci. Lett. 430 (1): 34–7. PMID 17997038. doi:10.1016/j.neulet.2007.10.011.
- Walsh H, Govind AP, Mastro R, et al. (2008). "Up-regulation of nicotinic receptors by nicotine varies with receptor subtype". J. Biol. Chem. 283 (10): 6022–32. PMID 18174175. doi:10.1074/jbc.M703432200.
- Nguyen HN, Rasmussen BA, Perry DC (2003). "Subtype-selective up-regulation by chronic nicotine of high-affinity nicotinic receptors in rat brain demonstrated by receptor autoradiography". J. Pharmacol. Exp. Ther. 307 (3): 1090–7. PMID 14560040. doi:10.1124/jpet.103.056408.
- Pons S, Fattore L, Cossu G, et al. (November 2008). "Crucial role of α4 and α6 nicotinic acetylcholine receptor subunits from ventral tegmental area in systemic nicotine self-administration". J. Neurosci. 28 (47): 12318–27. PMC 2819191. PMID 19020025. doi:10.1523/JNEUROSCI.3918-08.2008.
- Amir Levine et al. (2011). "Molecular Mechanism for a Gateway Drug: Epigenetic Changes Initiated by Nicotine Prime Gene Expression by Cocaine". Sci Transl Med 3 (107): 107ra109. doi:10.1126/scitranslmed.3003062.
- Volkow ND (November 2011). "Epigenetics of nicotine: another nail in the coughing". Sci Transl Med 3 (107): 107ps43. PMC 3492949. PMID 22049068. doi:10.1126/scitranslmed.3003278.
- Yoshida T, Sakane N, Umekawa T, Kondo M (Jan 1994). "Effect of nicotine on sympathetic nervous system activity of mice subjected to immobilization stress". Physiol. Behav. 55 (1): 53–7. PMID 8140174. doi:10.1016/0031-9384(94)90009-4.
- King G, Yerger VB, Whembolua GL, Bendel RB, Kittles R, Moolchan ET (June 2009). "Link between facultative melanin and tobacco use among African Americans". Pharmacol. Biochem. Behav. 92 (4): 589–96. PMID 19268687. doi:10.1016/j.pbb.2009.02.011.
- Elaine N. Marieb and Katja Hoehn (2007). Human Anatomy & Physiology (7th Ed.). Pearson. pp. ?. ISBN 0-8053-5909-5.[page needed]
- Bhalala, Oneil (Spring 2003). "Detection of Cotinine in Blood Plasma by HPLC MS/MS". MIT Undergraduate Research Journal 8: 45–50.
- Okamoto M, Kita T, Okuda H, Tanaka T, Nakashima T (Jul 1994). "Effects of aging on acute toxicity of nicotine in rats". Pharmacol Toxicol. 75 (1): 1–6. PMID 7971729. doi:10.1111/j.1600-0773.1994.tb00316.x.
- Toxicology and Applied Pharmacology. Vol. 44, Pg. 1, 1978.
- "Consumer Updates: Nicotine Replacement Therapy Labels May Change". FDA. April 1, 2013.
- Lockhart LP (1933). "Nicotine poisoning". Br Med J 1 (3762): 246–7. doi:10.1136/bmj.1.3762.246-c.
- Cardinale A et al. Nicotine: specific role in angiogenesis, proliferation and apoptosis Crit Rev Toxicol. 2012 Jan;42(1):68-89. PMID 22050423
- Hecht SS (July 1999). "Tobacco smoke carcinogens and lung cancer". J. Natl. Cancer Inst. 91 (14): 1194–210. PMID 10413421. doi:10.1093/jnci/91.14.1194.
- Wu WK, Cho CH (April 2004). "The pharmacological actions of nicotine on the gastrointestinal tract". J. Pharmacol. Sci. 94 (4): 348–58. PMID 15107574. doi:10.1254/jphs.94.348.
- Chowdhury P, Udupa KB (December 2006). "Nicotine as a mitogenic stimulus for pancreatic acinar cell proliferation". World J. Gastroenterol. 12 (46): 7428–32. PMID 17167829.
- Wong HP, Yu L, Lam EK, Tai EK, Wu WK, Cho CH (June 2007). "Nicotine promotes colon tumor growth and angiogenesis through beta-adrenergic activation". Toxicol. Sci. 97 (2): 279–87. PMID 17369603. doi:10.1093/toxsci/kfm060.
- Natori T, Sata M, Washida M, Hirata Y, Nagai R, Makuuchi M (October 2003). "Nicotine enhances neovascularization and promotes tumor growth". Mol. Cells 16 (2): 143–6. PMID 14651253.
- Ye YN, Liu ES, Shin VY, Wu WK, Luo JC, Cho CH (January 2004). "Nicotine promoted colon cancer growth via epidermal growth factor receptor, c-Src, and 5-lipoxygenase-mediated signal pathway". J. Pharmacol. Exp. Ther. 308 (1): 66–72. PMID 14569062. doi:10.1124/jpet.103.058321.
- Davis R, Rizwani W, Banerjee S, et al. (2009). "Nicotine promotes tumor growth and metastasis in mouse models of lung cancer". In Pao, William. PLoS ONE 4 (10): e7524. Bibcode:2009PLoSO...4.7524D. PMC 2759510. PMID 19841737. doi:10.1371/journal.pone.0007524.
- Behnke M, et al. Prenatal substance abuse: short- and long-term effects on the exposed fetus Pediatrics. 2013 Mar;131(3):e1009-24. PMID 23439891
- http://oehha.ca.gov/prop65/prop65_list/files/P65single121809.pdf[full citation needed]
- Sabha M, Tanus-Santos JE, Toledo JC, Cittadino M, Rocha JC, Moreno H (August 2000). "Transdermal nicotine mimics the smoking-induced endothelial dysfunction". Clin. Pharmacol. Ther. 68 (2): 167–74. PMID 10976548. doi:10.1067/mcp.2000.108851.
- Zhang S, Day I, Ye S (February 2001). "Nicotine induced changes in gene expression by human coronary artery endothelial cells". Atherosclerosis 154 (2): 277–83. PMID 11166759. doi:10.1016/S0021-9150(00)00475-5.
- Hawkins BT, Brown RC, Davis TP (February 2002). "Smoking and ischemic stroke: a role for nicotine?". Trends Pharmacol. Sci. 23 (2): 78–82. PMID 11830264. doi:10.1016/S0165-6147(02)01893-X.
- Raval AP, Bhatt A, Saul I (July 2009). "Chronic nicotine exposure inhibits 17beta-estradiol-mediated protection of the hippocampal CA1 region against cerebral ischemia in female rats". Neurosci. Lett. 458 (2): 65–9. PMID 19442878. doi:10.1016/j.neulet.2009.04.021.
- National Institute of Drug Abuse. Page last updated July 2012. Is Nicotine Addictive? Accessed June 3, 2014
- US Center for Disease Control. Page last updated: February 7, 2014 http://www.cdc.gov/tobacco/data_statistics/fact_sheets/cessation/quitting/index.htm#dependence Fact Sheet: Quitting Smoking] Accessed June 3, 2014
- Blakeslee, Sandra (1987-03-29). "Nicotine: Harder to Kick...Than Heroin". The New York Times.
- "Division of Periodontology: Tobacco Use Cessation Program". .umn.edu. Retrieved 2012-12-19.
- Yoshida T, Nishioka H, Nakamura Y, Kondo M (November 1984). "Reduced norepinephrine turnover in mice with monosodium glutamate-induced obesity". Metab. Clin. Exp. 33 (11): 1060–3. PMID 6493048. doi:10.1016/0026-0495(84)90238-5.
- Kenny PJ, Markou A (Jun 2006). "Nicotine self-administration acutely activates brain reward systems and induces a long-lasting increase in reward sensitivity". Neuropsychopharmacology 31 (6): 1203–11. PMID 16192981. doi:10.1038/sj.npp.1300905.
- Peterson EC, Owens SM (June 2009). "Designing immunotherapies to thwart drug abuse". Mol. Interv. 9 (3): 119–24. PMC 2743871. PMID 19592672. doi:10.1124/mi.9.3.5.
- Benowitz NL, Hukkanen J, Jacob P (2009). Nicotine Chemistry, Metabolism, Kinetics and Biomarkers. "Nicotine Psychopharmacology". Handbook of experimental pharmacology. Handbook of Experimental Pharmacology 192 (192): 29–60. ISBN 978-3-540-69246-1. PMC 2953858. PMID 19184645. doi:10.1007/978-3-540-69248-5_2.
- Baselt, Randall Clint (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Biomedical Publications. pp. 1103–7. ISBN 978-0-9626523-7-0.
- Mündel, T. and Jones, D. A. (2006). "Effect of transdermal nicotine administration on exercise endurance in men". Exp Physiol 91 (4): 705–713. PMID 16627574. doi:10.1113/expphysiol.2006.033373.
- Stead LF, Perera R, Bullen C, Mant D, Lancaster T (2008). "Nicotine replacement therapy for smoking cessation". In Stead, Lindsay F. Cochrane Database Syst Rev (1): CD000146. PMID 18253970. doi:10.1002/14651858.CD000146.pub3.
- Millstone, Ken (February 13, 2007). "Nixing the patch: Smokers quit cold turkey". Columbia.edu News Service. Retrieved May 23, 2010.
- Doran, Christopher M.; Valenti, Lisa; Robinson, Maxine; Britt, Helena; Mattick, Richard P. (2006). "Smoking status of Australian general practice patients and their attempts to quit". Addictive Behaviors 31 (5): 758–66. PMID 16137834. doi:10.1016/j.addbeh.2005.05.054.
- Gallup Poll (July 31, 2013), Most U.S. Smokers Want to Quit, Have Tried Multiple Times, Gallup, retrieved December 17, 2013
- Pierce, John P.; Cummins, Sharon E.; White, Martha M.; Humphrey, Aimee; Messer, Karen (2012). "Quitlines and Nicotine Replacement for Smoking Cessation: Do We Need to Change Policy?". Annual Review of Public Health 33: 341–56. PMID 22224888. doi:10.1146/annurev-publhealth-031811-124624.
- Cohen DJ, Doucet M, Cutlip DE, Ho KK, Popma JJ, Kuntz RE (August 2001). "Impact of smoking on clinical and angiographic restenosis after percutaneous coronary intervention: another smoker's paradox?". Circulation 104 (7): 773–8. PMID 11502701. doi:10.1161/hc3201.094225.
- Longmore, M., Wilkinson, I., Torok, E. Oxford Handbook of Clinical Medicine (5th ed.). p. 232.
- Green JT, Richardson C, Marshall RW, Rhodes J, McKirdy HC, Thomas GA, Williams GT (November 2000). "Nitric oxide mediates a therapeutic effect of nicotine in ulcerative colitis". Aliment. Pharmacol. Ther. 14 (11): 1429–34. PMID 11069313. doi:10.1046/j.1365-2036.2000.00847.x.
- Goedert JJ, Vitale F, Lauria C, Serraino D, Tamburini M, Montella M, Messina A, Brown EE, Rezza G, Gafà L, Romano N (November 2002). "Risk factors for classical Kaposi's sarcoma". J. Natl. Cancer Inst. 94 (22): 1712–8. PMID 12441327. doi:10.1093/jnci/94.22.1712. Lay summary – United Press International (March 29, 2001).
- Lain KY, Powers RW, Krohn MA, Ness RB, Crombleholme WR, Roberts JM (November 1999). "Urinary cotinine concentration confirms the reduced risk of preeclampsia with tobacco exposure". Am. J. Obstet. Gynecol. 181 (5 Pt 1): 1192–6. PMID 10561644. doi:10.1016/S0002-9378(99)70107-9.
- Hjern A, Hedberg A, Haglund B, Rosén M (June 2001). "Does tobacco smoke prevent atopic disorders? A study of two generations of Swedish residents". Clin. Exp. Allergy 31 (6): 908–14. PMID 11422156. doi:10.1046/j.1365-2222.2001.01096.x.
- Melton L (June 2006). "Body Blazes". Scientific American 294 (6): 24. Bibcode:2006SciAm.294f..24M. PMID 16711354. doi:10.1038/scientificamerican0606-24.
- Peters R, Poulter R, Warner J, Beckett N, Burch L, Bulpitt C (2008). "Smoking, dementia and cognitive decline in the elderly, a systematic review". BMC Geriatr 8: 36. PMC 2642819. PMID 19105840. doi:10.1186/1471-2318-8-36.
- Henningfield JE, Zeller M (2009). "Nicotine psychopharmacology: policy and regulatory". Handb Exp Pharmacol. Handbook of Experimental Pharmacology 192 (192): 511–34. ISBN 978-3-540-69246-1. PMID 19184661. doi:10.1007/978-3-540-69248-5_18.
- Quik, Maryka; Parameswaran, Neeraja; McCallum, Sarah E.; Bordia, Tanuja; Bao, Shanshan; McCormack, Alison; Kim, Amy; Tyndale, Rachel F.; Langston, J. William; Di Monte, Donato A. (2006). "Chronic oral nicotine treatment protects against striatal degeneration in MPTP-treated primates". Journal of Neurochemistry 98 (6): 1866–75. PMID 16882311. doi:10.1111/j.1471-4159.2006.04078.x. Lay summary – WebMD (August 11, 2006).
- De Lau, L.M.L.; Koudstaal, P. J.; Witteman, J. C.M.; Hofman, A.; Breteler, M. M.B. (2006). "Dietary folate, vitamin B12, and vitamin B6 and the risk of Parkinson disease". Neurology 67 (2): 315–8. PMID 16864826. doi:10.1212/01.wnl.0000225050.57553.6d. Lay summary – NutraIngredients (August 2, 2006).
- Quik, Maryka; Cox, Heather; Parameswaran, Neeraja; O'Leary, Kathryn; Langston, J. William; Di Monte, Donato (2007). "Nicotine reduces levodopa-induced dyskinesias in lesioned monkeys". Annals of Neurology 62 (6): 588–96. PMID 17960553. doi:10.1002/ana.21203. Lay summary – Reuters (October 24, 2007).
- Yu W, Mechawar N, Krantic S, Quirion R (November 2011). "α7 Nicotinic receptor activation reduces β-amyloid-induced apoptosis by inhibiting caspase-independent death through phosphatidylinositol 3-kinase signaling". J. Neurochem. 119 (4): 848–58. PMID 21884524. doi:10.1111/j.1471-4159.2011.07466.x.
- Willoughby, John O.; Pope, Kenneth J.; Eaton, Vaughn (2003). "Nicotine as an Antiepileptic Agent in ADNFLE: An N-of-One Study". Epilepsia 44 (10): 1363. PMID 12919397. doi:10.1046/j.1528-1157.2003.11903.x.
- de Leon J, Tracy J, McCann E, McGrory A, Diaz FJ (Jul 2002). "Schizophrenia and tobacco smoking: a replication study in another US psychiatric hospital". Schizophr Res. 56 (1–2): 55–65. PMID 12084420. doi:10.1016/S0920-9964(01)00192-X.
- de Leon J, Dadvand M, Canuso C, White AO, Stanilla JK, Simpson GM (Mar 1995). "Schizophrenia and smoking: an epidemiological survey in a state hospital". Am J Psychiatry 152 (3): 453–5. PMID 7864277.
- Aguilar MC, Gurpegui M, Diaz FJ, de Leon J (Mar 2005). "Nicotine dependence and symptoms in schizophrenia: naturalistic study of complex interactions". Br J Psychiatry 186 (3): 215–21. PMID 15738502. doi:10.1192/bjp.186.3.215.
- McClernon, F. Joseph; Hiott, F. Berry; Westman, Eric C.; Rose, Jed E.; Levin, Edward D. (2006). "Transdermal nicotine attenuates depression symptoms in nonsmokers: A double-blind, placebo-controlled trial". Psychopharmacology 189 (1): 125–33. PMID 16977477. doi:10.1007/s00213-006-0516-y. Lay summary – Duke Medicine News and Communications (September 12, 2006).
- "Attention-Deficit Hyperactivity Disorder". Retrieved 21 September 2009.
- Mineur YS, Picciotto MR (December 2010). "Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis". Trends Pharmacol. Sci. 31 (12): 580–6. PMC 2991594. PMID 20965579. doi:10.1016/j.tips.2010.09.004.
- Pasquini M, Garavini A, Biondi M (January 2005). "Nicotine augmentation for refractory obsessive-compulsive disorder. A case report". Prog. Neuropsychopharmacol. Biol. Psychiatry 29 (1): 157–9. PMID 15610960. doi:10.1016/j.pnpbp.2004.08.011.
- Lundberg S, Carlsson A, Norfeldt P, Carlsson ML (November 2004). "Nicotine treatment of obsessive-compulsive disorder". Prog. Neuropsychopharmacol. Biol. Psychiatry 28 (7): 1195–9. PMID 15610934. doi:10.1016/j.pnpbp.2004.06.014.
- Tizabi Y, Louis VA, Taylor CT, Waxman D, Culver KE, Szechtman H (January 2002). "Effect of nicotine on quinpirole-induced checking behavior in rats: implications for obsessive-compulsive disorder". Biol. Psychiatry 51 (2): 164–71. PMID 11822995. doi:10.1016/S0006-3223(01)01207-0.
- Thomas GA, Rhodes J, Green JT, Richardson C (May 2000). "Role of smoking in inflammatory bowel disease: implications for therapy". Postgrad Med J 76 (895): 273–9. PMC 1741576. PMID 10775279. doi:10.1136/pmj.76.895.273.
- Rubin DT, Hanauer SB (August 2000). "Smoking and inflammatory bowel disease". Eur J Gastroenterol Hepatol 12 (8): 855–62. PMID 10958212. doi:10.1097/00042737-200012080-00004.
- "Effective Clinical Tobacco Intervention". Therapeutics Letter (21): 1–4. September–October 1997.
- Lagrue, Gilbert; Cormier, Anne (June 2001). "Des récepteurs nicotiniques à la dépendance tabagique : Perspectives thérapeutiques" [From nicotinic receptors to smoking dependence: Therapeutic prospects]. Alcoologie et addictologie (in French) 23 (2): 39S–42S. ISSN 1620-4522. INIST:1081618.
- Orsini, Jean-Claude (June 2001). "Dépendance tabagique et contrôle central de la glycémie et de l'appétit" [Dependence on tobacco smoking and brain systems controlling glycemia and appetite]. Alcoologie et addictologie (in French) 23 (2 Suppl): 28S–36S. ISSN 1620-4522. INIST:1081638.
- Chen, Hui; Vlahos, Ross; Bozinovski, Steve; Jones, Jessica; Anderson, Gary P; Morris, Margaret J (2004). "Effect of Short-Term Cigarette Smoke Exposure on Body Weight, Appetite and Brain Neuropeptide Y in Mice". Neuropsychopharmacology 30 (4). PMID 15508020. doi:10.1038/sj.npp.1300597. Lay summary – The University of Melbourne (1 November 2004).
- Pomerleau OF, Pomerleau CS (1984). Neuroregulators and the reinforcement of smoking: Towards a biobehavioral explanation. Neuroscience and Biobehavioral Reviews, 8:503-513.
- Pomerleau OF, Rosecrans J (1989). Neuroregulatory effects of nicotine. Psychoneuroendocrinology 14:407-423.
- Rusted J, Graupner L, O'Connell N, Nicholls C (August 1994). "Does nicotine improve cognitive function?". Psychopharmacology (Berl.) 115 (4): 547–9. PMID 7871101. doi:10.1007/BF02245580.
- Easton, John (March 28, 2002). "Nicotine extends duration of pleasant effects of dopamine". The University of Chicago Chronicle 21 (12).
- "Erowid Nicotine Vault : Dosage". Erowid.org. 2011-10-14. Retrieved 2012-12-19.
- Golding, J. F.; Mangan, G. L. (1989). "Factors Governing Recruitment to and Maintenance of Smoking". In Einstein, Stanley. Drug and Alcohol Use. pp. 101–17. ISBN 978-1-4899-0890-2. doi:10.1007/978-1-4899-0888-9_9.
- Nesbitt P (1969). Smoking, physiological arousal, and emotional response. Unpublished doctoral dissertation, Columbia University.
- Parrott AC (January 1998). "Nesbitt's Paradox resolved? Stress and arousal modulation during cigarette smoking". Addiction 93 (1): 27–39. PMID 9624709. doi:10.1046/j.1360-0443.1998.931274.x.
- US Code of Federal Regulations. 7 CFR 205.602 - Nonsynthetic substances prohibited for use in organic crop production
- Staff, IFOAM. Criticisms and Frequent Misconceptions about Organic Agriculture: The Counter-Arguments: Misconception Number 7
- USEPA (29 October 2008). "Nicotine; Notice of Receipt of Request to Voluntarily Cancel a Pesticide Registration". Federal Register: 64320–64322. Retrieved 8 April 2012.
- USEPA (3 June 2009). "Nicotine; Product Cancellation Order". Federal Register: 26695–26696. Retrieved 8 April 2012.
- Bilkei-Gorzo A, Rácz I, Michel K, Darvas M, Rafael Maldonado López, Zimmer A. (2008). "A common genetic predisposition to stress sensitivity and stress-induced nicotine craving". Biol. Psychiatry 63 (2): 164–71. PMID 17570348. doi:10.1016/j.biopsych.2007.02.010.
- Gorrod, John W.; Peyton, Jacob,III, eds. (November 16, 1999). Analytical Determination of Nicotine and Related Compounds and their Metabolites. Amsterdam: Elsevier. ISBN 978-0-08-052551-8.
- Willoughby JO, Pope KJ, Eaton V (Sep 2003). "Nicotine as an antiepileptic agent in ADNFLE: an N-of-one study". Epilepsia 44 (9): 1238–40. PMID 12919397. doi:10.1046/j.1528-1157.2003.11903.x.
- Minna JD (Jan 2003). "Nicotine exposure and bronchial epithelial cell nicotinic acetylcholine receptor expression in the pathogenesis of lung cancer". J Clin Invest. 111 (1): 31–3. PMC 151841. PMID 12511585. doi:10.1172/JCI17492.
- Fallon JH, Keator DB, Mbogori J, Taylor D, Potkin SG (Mar 2005). "Gender: a major determinant of brain response to nicotine". Int J Neuropsychopharmacol. 8 (1): 17–26. PMID 15579215. doi:10.1017/S1461145704004730.
- West KA, Brognard J, Clark AS, et al. (Jan 2003). "Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells". J Clin Invest. 111 (1): 81–90. PMC 151834. PMID 12511591. doi:10.1172/JCI16147.
- National Institute on Drug Abuse
- Erowid information on tobacco
|40x40px||Wikimedia Commons has media related to Nicotine.|
- Description of nicotine mechanisms
- Erowid Nicotine Vault : Nicotine Material Safety Data Sheet
- Thomas, Gareth AO; Rhodes, John; Ingram, John R (2005). "Mechanisms of Disease: Nicotine—a review of its actions in the context of gastrointestinal disease". Nature Clinical Practice Gastroenterology & Hepatology 2 (11): 536. doi:10.1038/ncpgasthep0316.
- CDC - NIOSH Pocket Guide to Chemical Hazards