Nicotine

Nicotine
Chemical Nomenclature
Common names	Nicotine
Systematic name	(S)-3-[1-Methylpyrrolidin-2-yl]pyridine
Class Membership
Psychoactive class	Stimulant
Chemical class	Pyridine / Pyrrolidine
Routes of Administration
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section. Smoked Dosage Threshold 0.2 - 0.3 mg Light 0.3 - 0.8 mg Common 0.8 - 1.5 mg Strong 1.5 - 3.5 mg Heavy 3.5 mg + Duration Total 10 - 30 minutes Onset 5 - 60 seconds After effects 1 - 3 hours Buccal Dosage Bioavailability 10-20% Threshold 3 - 6 mg Light 6 - 8 mg Common 8 - 12 mg Strong 12 - 22 mg Heavy 22 mg + Duration Total 20 - 45 minutes Onset 1 - 5 minutes Peak 2 - 4 minutes After effects 0.5 - 1 hours DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.

Nicotine is a naturally-occurring stimulant substance of the pyrrolidinylpyridine class. It is the principle alkaloid found in the nightshade family of plants.^{[citation needed]} As the chief ingredient of the tobacco used in cigarettes, cigars, and snuff, it is one of the most widely used substances in the world.^{[citation needed]}

Nicotine acts as an agonist at most nicotinic acetylcholine receptors (nAChRs).^{[citation needed]} It is used as an antiherbivore agent to deter plant predation and has been used as an insecticide in the past.^{[citation needed]}

Unlike other psychoactive substances, nicotine is reported to have a unique biphasic effect in which inhaling it in short puffs produces a stimulant effect, while deep drags produces a relaxing one.

Nicotine is a highly addictive substance. Beyond addiction, both short and long-term nicotine exposure have not been established as dangerous to adults,^{[citation needed]} except among certain vulnerable groups.^{[citation needed]} At sufficiently high doses, nicotine is associated with poisonings and is potentially lethal.^{[citation needed]} Nicotine as a tool for quitting smoking has a good safety history.^{[citation needed]} While the link between tobacco use and cancer are well-established, there is inadequate research to show that nicotine itself is associated with cancer in humans.^{[citation needed]}

History and culture

This History and Culture section is a stub. As such, it may contain incomplete or wrong information. You can help by expanding it.

Crude nicotine was known by 1571, and the compound was obtained in purified form in 1828; the correct molecular formula was established in 1843, and the first laboratory synthesis was reported in 1904.

Nicotiana rustica has been used by the Mapacho (South America)^[1] and the thuoc lao (thuốc lào) (Vietnam) people for spiritual purposes.

Chemistry

Nicotine (3-[(2S)-1-methylpyrrolidin-2-yl]pyridine) is a naturally occurring bicyclic compound comprised of a pyridine ring attached to the second carbon of a pyrrolidine ring that has a methyl substituent on the nitrogen. Pyridine is an unsaturated six-membered ring structurally related to benzene but with a nitrogen member. Nicotine additionally contains a substituted pyrrolidine ring, which is a saturated five-membered ring with one nitrogen member. These rings are bridged from the R₃ position of the pyridine ring to the R₂ position of the pyrrolidine ring.

Both optical enantiomers of nicotine are active, with the naturally occurring levorotatory enantiomer being more active and more toxic than the dextrorotatory. In its basic form, it is an oily liquid that is miscible with water. However, as a nitrogenous base, nicotine readily forms stable, water-soluble salts when acidified.

Pharmacology

Nicotine produces its stimulating effects by agonizing nicotinic acetylcholine receptors, causing the liver to release glucose and the adrenal medulla to release epinephrine (adrenaline).

Once it reaches the brain, nicotine stimulates the release of many neurotransmitters and hormones, including acetylcholine, norepinephrine, epinephrine, arginine vasopressin, serotonin, dopamine, and β-endorphin^[2][3], which are responsible for the majority of its psychoactive effects.

By increasing the level of acetylcholine in the brain, nicotine enhances concentration. Norepinephrine release causes increased alertness and arousal. With low doses, nicotine enhances the action of norepinephrine and dopamine, which produces typical psychostimulation. Nicotine also has sedative effects as produced by the release of β-endorphin (which reduces anxiety) and enhances the action of serotonin and opioids (which causes sedation).^{[citation needed]}

Bioavailability

• Oral: 20% - 45%
• Intranasal: 53%
• Transdermal: 68%

Metabolism

Nicotine has a half-life of 1 - 2 hours when administered in a single dose and an active metabolite (cotinine) with a half-life of 20 hours. Nicotine and cotinine are further glucuronidated by UGT2B10.^[4]

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. These effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances of inducing a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Experience reports

There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:

• Erowid Experience Vaults: Nicotine

Forms

Generic smoking tobacco next to branded and pre-packaged Newport Menthol King cigarettes.

Smokeless swedish snus

Tobacco

The most common source of nicotine is Nicotiana tabacum, constituting 0.6% - 3.0% of its dry weight.^[5] It is also present in other species of Nightshade (Solanaceae), such as Indian tobacco (Nicotiana rustica). Tobacco for smoking is most commonly sold as cigarettes but may also be sold as cigars, which differ from cigarettes by having a tobacco leaf wrapper instead of the paper wrapper used in cigarettes. Loose tobacco for hand-rolling cigarettes and cigars, or for smoking in pipes/hookahs is also commonly available. Tobacco products not intended for smoking are also marketed. These include snuffs which are insufflated and chewing tobacco, also known as snus.

Replacement therapies

Nicotine is also extracted from tobacco and reformulated into products intended to assist users who wish to cease use of tobacco products like cigarettes. Popular products include sublingual lozenges and sprays, skin patches, inhalers, and solutions used for oral use or in conjunction with a vaporizer.

E-cigarettes and vaporizers

More recently, nicotine in liquid forms (commonly called e-liquid) intended for vaporizing in electronic cigarettes has become popular as an alternative to smoking. Unlike products intended to assist in smoking cessation, e-cigarettes are not typically licensed or marketed as medical devices.

Moist dipping tobacco

Dipping tobacco (dip, chew, chaw, snuff, etc.) is a form of tobacco that is cut in fine, medium, long, or extra long cut shreds and is placed in the gingiva of either side and floor of the mouth. It is fermented, unlike Swedish snus, which is pasteurized. It is known to produce excess saliva that needs to be spat out, otherwise the user may experience nausea. It gives a buzz and feeling of lightheadedness to the user. Dip may be put into pouches to produce an Americanized version of Swedish snus.

Swedish snus

Swedish snus is a form of tobacco that is cut and/or ground and put into small, soft pouches, which the user puts in the space under the upper lip and gum (gingiva). Nicotine passes into the bloodstream through the process of diffusion. Snus is available without any taste additives as a natural taste, but is also available in various taste options, from menthol vanilla, bergamot, citrus and others.

Toxicity and harm potential

Radar plot showing relative physical harm, social harm, and dependence of nicotine in the form tobacco^[6]

It is strongly recommended that one use harm reduction practices when using this substance.

Lethal dosage

Nicotine has an estimated oral LD₅₀ of 6.5 - 13 mg/kg in humans, which is much lower than many other common stimulants. It is unlikely that overdose can be achieved by smoking tobacco. However, coadministration with other sources of nicotine such as patches or gum may potentially be dangerous.

Nicotine readily passes through the dermis and into the bloodstream upon contact with skin, so safety precautions should be taken when handling it in its pure form.

Flavored e-liquids intended for use in e-cigarette devices can present a particular danger to children, and there have been cases recorded where children have mistakenly consumed e-liquid products with fatal results.^[7]

Tolerance and addiction potential

Nicotine activates the reward system (mesolimbic pathway) of the brain, which is responsible for its addictive nature. Because of this, tobacco smoking is extremely addictive with a high potential for abuse. When addiction has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage.

Chronic use of nicotine, as with many other addictive substances, downregulates the production of dopamine and other stimulatory neurotransmitters and also desensitizes nicotinic acetylcholine receptors. In response, the brain upregulates the number of receptors presented. The net effect is an increase in sensitivity to the reward system; the opposite of the decrease in sensitivity as caused by addictive substances like cocaine and heroin.

Tolerance to the effects of this compound rapidly develops with prolonged and repeated use. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). Nicotine does not present a cross-tolerance with other dopaminergic stimulants, meaning that after the use of nicotine all stimulants will not have a reduced effect.

Following discontinuation of nicotine, receptors may take several months to return to baseline.

Pregnancy

Nicotine has been indicated in the increased frequency of congenital disabilities and has been correlated with the increase of attention deficit hyperactivity disorder in children.

Legal status

Nicotine is legal nearly all over the world and is one of the most popularly used substances. The sale of tobacco products are usually restricted to adults, and they are often heavily taxed.

• Bhutan: Tobacco products are legal, but their public use is restricted to specific smoke-friendly areas.^[8]

See also

• Responsible use
• Stimulants
• Substituted pyrrolidine

External links

• Nicotine (Wikipedia)
• Nicotine (Erowid Vault)
• Nicotine (Drugs-Forum)

References