Nicotine
Nicotine is an
alkaloid found in the
nightshade family of plants (
Solanaceae), predominantly in
tobacco, and in lower quantities in
tomato,
potato,
eggplant (aubergine), and
green pepper. Nicotine alkaloids are also found in the leaves of the
coca plant. Nicotine constitutes 0.3 to 5% of the tobacco plant by dry weight, with biosynthesis taking place in the roots, and accumulates in the leaves. It is a potent nerve
poison and is included in many
insecticides.
In lower concentrations, the substance is a
stimulant and is one of the main factors responsible for the dependence-forming properties of
tobacco smoking.
Nicotine is a
hygroscopic, oily liquid that is
miscible with
water in its
base form. As a
nitrogenous base, nicotine forms
salts with
acids that are usually solid and water soluble. Nicotine easily penetrates the
skin. As shown by the physical data,
free base nicotine will burn at a temperature below its boiling point, and its vapors will combust at 95 °C in air despite a low vapor pressure. Because of this, most nicotine is burned when a cigarette is smoked; however, enough is inhaled to cause the body to form a powerful addiction.
In small doses nicotine has a stimulating effect, increasing activity, alertness and memory. Repeat users report only relief from the symptoms of nicotine withdrawal. It also increases the
heart rate and
blood pressure and reduces the appetite. In large doses nicotine may cause
vomiting and
nausea. Large doses are poisonous to most animals and to humans.
Nicotine seems to provide both a
stimulant and a
depressant effect, and it is possible that the effect it has at any time is determined by the mood of the user, the environment and the circumstances of use. Studies have suggested that low doses have a
stimulant effect, while higher doses have a
depressant effect.
Repeat users of nicotine very often develop a physical dependency to the chemical. A report released on
May 16,
1988, by
United States Surgeon General C. Everett Koop stated that the
addictive properties of nicotine are similar to those of
heroin and
cocaine. Physical withdrawal symptoms include irritability, headaches, anxiety, cognitive disturbances and sleep disruption. These symptoms peak at around 48–72
hours and taper off over two to six weeks.
Pharmacokinetics: As nicotine enters the body, it quickly gets distributed through the
bloodstream and can cross the
blood-brain barrier. On average it takes about seven seconds for the substance to reach the
brain. The amount of nicotine inhaled with tobacco smoke is a fraction of the amount contained in the tobacco leaves (most of the substance is destroyed by the heat). The amount of nicotine absorbed by the body from smoking depends on many factors, including the type of tobacco, whether the smoke is inhaled, and whether a filter is used. For chewing tobacco, often called
dip,
snuff, or
snus, which is held in the mouth between the lip and gum, the amount released into the body tends to be much greater than smoked tobacco.
Pharmacodynamics: Nicotine acts on the
nicotinic acetylcholine receptors. In small concentrations it increases the activity of these receptors, among other things leading to an increased flow of
adrenaline, a stimulating
hormone. The release of adrenaline causes an increase in heart rate, blood pressure and respiration, as well as higher
glucose levels in the blood.
Cotinine is a break-down product of nicotine which remains in the blood for up to 48 hours and can be used as an indicator of a person's exposure to smoke. In high doses, nicotine will cause a
depolarizing block of the nicotinic acetylcholine receptor, which is the reason for its
toxicity and its effectiveness as an
insecticide.
In addition, nicotine increases
dopamine levels in the reward circuits of the
brain. Studies have shown that smoking tobacco inhibits
monoamine oxidase (MAO), an
enzyme responsible for breaking down
monoaminergic neurotransmitters such as dopamine, in the brain. It is currently believed that nicotine by itself does not inhibit the production of
monoamine oxidase (MAO), but that other ingredients in inhaled tobacco smoke are believed to be responsible for this activity. In this way, it generates feelings of pleasure. This reaction is similar to that caused by
cocaine and
heroin and is another reason people keep smoking: to sustain high dopamine levels.
The
LD50 of nicotine is 50 mg/kg for
rats and 3 mg/kg for
mice. 40–60 mg can be a lethal dosage for adult human beings. This makes it an extremely deadly poison. It is more toxic than many other alkaloids such as
cocaine, which has a lethal dose of 1000mg.
The
carcinogenic properties of nicotine in standalone form, separate from tobacco smoke, have not been evaluated by the
IARC, and it has not been assigned to an official carcinogen group. The currently available literature indicates that nicotine, on its own, does not promote the development of
cancer in healthy tissue and has no
mutagenic properties. Its
teratogenic properties have not yet been adequately researched, and while the likelihood of birth defects caused by nicotine is believed to be very small or nonexistent, nicotine replacement product manufacturers recommend consultation with a physician before using a
nicotine patch or
nicotine gum while pregnant or nursing. However, nicotine and the increased acetylcholinic activity it causes have been shown to impede
apoptosis, which is one of the methods by which the body destroys unwanted cells (
programmed cell death). Since apoptosis helps to remove mutated or damaged cells that may eventually become cancerous, the inhibitory actions of nicotine creates a more favourable environment for cancer to develop. Thus nicotine plays an indirect role in
carcinogenesis. It is also important to note that its addictive properties are often the primary motivating factor for
tobacco smoking, contributing to the proliferation of cancer.
At least one study has concluded that exposure to nicotine alone, not simply as a component of cigarette smoke, could be responsible for some of the neuropathological changes observed in infants dying from
Sudden Infant Death Syndrome (SIDS).
[Machaalani et al. (2005) "Effects of postnatal nicotine exposure on apoptotic markers in the developing piglet brain"]It has been noted that the majority of people diagnosed with
schizophrenia smoke tobacco. Estimates for the number of schizophrenics that smoke range from 75% to 90%. It was recently argued that the increased level of smoking in schizophrenia may be due to a desire to
self-medicate with nicotine.
[ Schizophr. Res. 2002][Am. J. Psychiatry 1995] More recent research has found the reverse, that it is a risk factor without long-term benefit, used only for its short term effects.
[Br. J. Psychiatry 2005 ]However, research on nicotine as administered through a patch or gum is ongoing.
The primary therapeutic use of nicotine is in treating nicotine dependence (smoking). Controlled levels of nicotine are given to a patient through gums, dermal patches, or nasal sprays in an effort to wean them off of their dependence.
Recent studies have indicated that nicotine can be used to help adults suffering from
autosomal dominant frontal lobe epilepsy. The same areas that cause seizures in that form of
epilepsy are also responsible for processing nicotine in the brain.
Some research has also shown that nicotine can lessen symptoms of mild to moderate
ulcerative colitis.
Nicotine and its metabolites are being researched for the treatment of a number of disorders, including
ADHD,
Parkinson's Disease and
Alzheimer's Disease.
Nicotine is named after the tobacco plant
Nicotiana tabacum, which in turn is named after
Jean Nicot, a French ambassador, who sent tobacco and seeds from
Portugal to
Paris in
1550 and promoted their medicinal use. Nicotine was first isolated from the tobacco plant in
1828 by German chemists Posselt & Reimann. Its chemical empirical formula was described by Melsens in
1843, and it was first synthesized by A. Pictet and Crepieux in
1893.
*
Psychoactive drug*
Addiction*
Nicotine poisoning* Guardian article:
"Nicotine could soon be rehabilitated as a treatment for schizophrenia, Alzheimer's and Parkinson's diseases, as well as hyperactivity disorders."* Nicotine Therapy for ADNFLE:
"Nicotine as an antiepileptic agent in ADNFLE: An n-of-one study"* Minna, John D.:
"Nicotine exposure and bronchial epithelial cell nicotinic acetylcholine receptor expression in the pathogenesis of lung cancer"*
Fallon, J.H., et al. (2005) Gender: A major determinant of brain response to nicotine. International Journal of Neuropharmacology. 8:1-10. [
1]
* West, Kip A., et al.:
"Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells"*
National Institute on Drug Abuse*Powledge TM (2004) Nicotine as therapy. PLoS Biol 2(11): e404.: [
2]
