Nicotine

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The nicotine metabolite N-nitrosonornicotine is classified as a IARC Group 1 carcinogen

Nicotine in the mouth and stomach can react to form N-nitrosonornicotine,[1] a known type 1 carcinogen,[2] suggesting that consumption of non-tobacco forms of nicotine may still play a role in carcinogenesis.[3] This suggests that even non-tobacco forms of nicotine (except nicotine patches) might contribute to cancer risk.

Summary sheet: Nicotine
Nicotine
Nicotine.svg
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 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 1 - 3 hours
Onset 5 - 20 seconds
Come up 5 - 10 seconds
Peak 2 - 5 minutes
Offset 1 - 2 hours
After effects 1 - 3 hours
Oral
Dosage
Threshold 0.2 mg
Light 0.5 - 1 mg
Common 1 - 2 mg
Strong 2 - 4 mg
Heavy 4 mg +
Duration
Total 5 - 7 hours
Onset 20 - 40 minutes
Come up 60 - 90 minutes
Peak 60 - 90 minutes
Offset 2.5 - 3.5 hours
After effects 2 - 4 hours
Buccal
Dosage
Threshold 0.2 mg
Light 0.5 - 2 mg
Common 2 - 4 mg
Strong 4 - 6 mg
Heavy 6 mg +
Duration
Total 45 - 90 minutes
Onset 3 - 15 minutes
Come up 3 - 15 minutes
Peak 5 - 20 minutes
Offset 1 - 2 hours
After effects 2 - 6 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.

Interactions

Nicotine is a naturally-occurring stimulant substance, and after a sustained use, a depressant (see Pituri).[4]

Nicotine is a substance of the pyridine and pyrrolidine classes. It is the principal alkaloid found in the nightshade family of plants.[5] It produces its effects by binding to nicotinic acetylcholine receptors (nAChRs).[6]

As the chief ingredient of the tobacco used in cigarettes, cigars, and snuff, nicotine is one of the most widely used substances in the world.[7] It is also used as an antiherbivore agent to deter plant predation and has been used as an insecticide in the past. [8]

Subjective effects include stimulation, focus enhancement, motivation enhancement, anxiety suppression, and mild euphoria. The stimulating and anxiety-suppressing effects are considered mild compared to other substances, but can nevertheless promote compulsive redosing.

Unlike many other psychoactive substances, nicotine in the form of tobacco 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 overdoses, even mild ones, are reported to be highly unpleasant and result in significant nausea and light-headedness.

Nicotine is well-studied and known to be highly addictive. At sufficiently high doses, it can potentially be deadly, though serious or fatal overdoses are rare. The major harms of nicotine addiction are associated with the negative health effects of chronic tobacco smoking, which include heart disease and various forms of cancer.[citation needed] While the link between tobacco use and cancer is well-established, various roles of nicotine in cancer initiation have also been found.[9]

Nicotine patches and nicotine-containing chewing gums are being currently used in nicotine-replacement therapy to help tobacco users quit.

It is highly advised to use harm reduction practices if using this substance.

History and culture

History icon.svg

This History and culture section is a stub.

As a result, 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)[10] and the thuoc lao (thuốc lào) (Vietnam) people for spiritual purposes.

Pituri

Pituri, also known as mingkulpa,[4] is a mixture of leaves and wood ash traditionally chewed as a stimulant (or, after extended use, a depressant) by Aboriginal Australians widely across the continent. At first, nicotine acts as a stimulant, boosting the production or availability of chemicals such as acetylcholine, norepinephrine, dopamine, beta-endorphin and serotonin in the brain and other parts of the body. After sustained use, though, the body's ability to maintain heightened levels of these chemicals is temporarily exhausted and nicotine begins to act as a depressant and in high doses may induce stupor or trance.[4]

The quid is chewed from time to time and held behind the lower lip or cheek for long periods, where the thin skin, richly endowed with blood vessels, readily absorbs the nicotine. It may be shared with others, passing from person to person until returned to its owner. It may be carried pressed behind the ear, under a breast or beneath a head- or arm-band – possibly acting as a nicotine patch. A fresh quid may be prepared and held in the mouth while sleeping, so that for some chewers nicotine absorption is constant.[4]

Dosage

"Analysis of dry leaf Nicotiana spp. preferred for use as pituri has demonstrated nicotine content as high as 11 mg/g".[11] For comparison, the nicotine content of nicotine pouches, or dipping tobacco, is typically listed directly on the package in mg/g and usually falls within a range of 4 to 14 mg/g.

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[12][13], 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

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.[14]

Subjective effects

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.


Physical effects
Child.svg

Cognitive effects
User.svg

Experience reports

Anecdotal reports which describe the effects of this compound within our experience index include:

Additional experience reports can be found here:

Forms

Main: List of tobacco products (Wikipedia)

Nicotine-only products

The nicotine in nicotine-only products typically use nicotine extracted from tobacco plants -- and the tobacco industry is linked to ethical issues.

E-cigarettes

Photo of device
A first-generation e-cigarette that resembles a tobacco cigarette

More recently, nicotine in liquid forms (commonly called e-liquid) intended for vaporizing in electronic cigarettes has become popular as an alternative to smoking. Illicit and unregulated E-cigarettes can contain a variety of additives that can be dangerous such as: Diacetyl (chemical linked to lung disease called bronchiolitis obliterans or better known as "popcorn lung"), Diethylene glycol (ingredient used in antifreeze, linked to lung diseases), Heavy metals (usually nickel, tin, or lead), benzene (A VOC found in car exhaust),and Acrolein (a herbicide, can cause irreversible lung damage).[16] It is important to note, however, that popcorn lung is not typically associated with E-cigarettes, these ingredients aren't typically found in E-cigarettes or E-liquid[17].

A 2023 report by the World Health Organization (WHO) found that 34 countries had banned the sale of e-cigarettes.[18]

Nicotine pouches

A single 3cm nicotine pouch

Nicotine pouches are white pouches usually made from plant fibers containing nicotine among other ingredients. They do not include tobacco leaf, dust, or stem.[19] The nicotine may either be derived from tobacco plants or may be synthetic. Nicotine pouches are described as either similar to or a tobacco-free version of snus.[19][20][21]

Nicotine replacement therapy (NRT)

Nicotine replacement therapy products contain purified nicotine in standardized dosages. They are 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.

Nicotine pastilles
NRT Type Device/package Availability How it works[22][23]
Patch Pouch Over-the-counter 16 or 24 hours sustained-release transdermal patch
Lozenge Blister pack Over-the-counter 20 to 30 minutes modified-release dosage tablet containing nicotine polacrilex
Sublingual tablets Blister pack Over-the-counter Quickly dissolves to releases nicotine through a hard candy
Nicotine gum Blister pack Over-the-counter Chewing the gum releases nicotine as a modified-release dosage
Mouth spray Mouth spray bottle Over-the-counter Spraying a mist into the mouth administers nicotine for buccal administration
Vapour inhalator Nicorette Inhalator: with 10 mg nicotine disposable cartridges Over-the-counter Resembles cigarettes; A disposable cartridge contains about 10 mg nicotine (about 40% is released). Multiple inhaling through the mouthpiece administers sufficient nicotine.
Pressurized Metered-dose inhaler (pMDI) Prescription Inhaling through the mouthpiece administers nicotine
Nasal spray Nasal spray bottle Prescription Spraying a pump bottle into the nose administers nicotine
Toothpicks Over-the-counter

Herbal tobacco

Herbal cigarettes

Herbal cigarette (also called tobacco-free cigarettes or nicotine-free cigarettes) are cigarettes that usually do not contain any tobacco or nicotine instead being composed of a mixture of various herbs and/or other plant material.[24] Herbal cigarettes can carry carcinogens.

Herbal smokeless tobacco

Herbal smokeless tobacco is any product that imitates types of smokeless tobacco (chewing tobacco, dipping tobacco, snuff, snus, etc.) but does not contain tobacco and nicotine, or may contain nicotine without tobacco. Like herbal cigarettes and electronic cigarettes, they are often used as a tobacco cessation aid.[25] Herbal smokeless tobacco use is an alternative to using smokeless tobacco that may help users quit.

Vaporizers

Liquid concentrate vaporizers can be used with vape liquids containing nicotine.

Dry herb vaporizers are designed for optimal temperature ranges specific to different herbs. Tobacco burns at a much higher temperature than most herbs used in vaporizers. Using tobacco in a dry herb vaporizer could result in combustion, which defeats the purpose of vaping (avoiding smoke) and could potentially create harmful byproducts.

Tobacco

See also: Nicotiana

Table from the 2010 ISCD study ranking various drugs (legal and illegal) based on statements by drug-harm experts. Tobacco was found to be the sixth overall most dangerous drug.[26]

The most common source of nicotine is Nicotiana tabacum, constituting 0.6% - 3.0% of its dry weight.[27] It is also present in other species of Nightshade (Solanaceae), such as Aztec tobacco (Nicotiana rustica).

Industrial tobacco production raises ethical concerns. Deforestation, child labor, and health risks for workers are major issues. For example, workers can experience a type of nicotine poisoning known as Green Tobacco Sickness (GTS), from absorbing nicotine directly through their skin when handling uncured tobacco leaves.

Heated tobacco products

On an open palm, a glossy plastic IQOS holder, the short paper-wrapped mini-cigarette that was in it, and the somewhat darkened tobacco plug removed from the end of the paper cylinder.
Tobacco film (right side) following use.

A heated tobacco product (HTP)[note 1] is a tobacco product that heats the tobacco at a lower temperature than conventional cigarettes.[60] These products contain nicotine, which is a highly addictive chemical.[60] The heat generates an aerosol or smoke to be inhaled from the tobacco, which contains nicotine[61] and other chemicals.[41][60] HTPs may also contain additives not found in tobacco,[62] including flavoring chemicals.[60] HTPs generally heat tobacco to temperatures under 600 °C (1100 °F),[60][38][63] a lower temperature than conventional cigarettes.[64]

The key difference between dry herb vaporizers and heated tobacco products is that vaporizers heat loose plant material (like herbs) to avoid combustion, while heated tobacco products use pre-filled tobacco sticks/capsules and aim to heat, not burn, the tobacco to release nicotine. However, some heated tobacco products (for example some PAX products) are designed to be used with both tobacco and cannabis buds.

Smoked tobacco

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

"Of the more than 7,000 chemicals in tobacco smoke, at least 250 are known to be harmful, including hydrogen cyanide, carbon monoxide, and ammonia." - National Cancer Institute

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.

Smokeless tobacco

In recent years a popular method of snuff insufflation has been the snuff bullet.
Dipping tobacco is placed between the lip and the gum (sublabial administration).

As of 2017, the World Health Organization states that "Smokeless tobacco use is a significant part of the overall world tobacco problem."[65] As of 2015, the American Cancer Society states that "Using any kind of spit or smokeless tobacco is a major health risk. It's less lethal than smoking tobacco, but less lethal is a far cry from safe."[66]

Types of smokeless tobacco include:

  • Mixed routes of administration:
    • Kuber, a smokeless tobacco product known for its highly addictive properties and its unique presentation disguised as a mouth freshener. Users commonly add it to tea or consume it directly by placing a pinch under the lower lip.[67]
  • Nasal administration:
    • Snuff, a type of tobacco that is inhaled or "snuffed" into the nasal cavity. Traditionally, a specialized tool called a snuff spoon was used for this purpose. However, modern users may simply pinch the snuff between their thumb and forefinger or use pre-measured packets.
  • Oral mucosa (buccal, sublabial, or sublingual):
    • Chewing tobacco, a type of tobacco that is chewed
    • Creamy snuff, a fluid tobacco mixture marketed as a dental hygiene aid, albeit used for recreation
    • Dipping tobacco, a type of tobacco that is placed between the lower or upper lip and gums. This form of tobacco (Hindi: Khaini) is commonly used in Indian subcontinent. [68] It is the second most common form of tobacco consumption in India, after cigarrette smoking. [69]
    • Dissolvable tobacco, a variation on chewing tobacco that completely dissolves in the mouth
    • Gutka, a mixture of tobacco, areca nut, and various flavoring sold in South Asia
    • Iqmik, an Alaskan tobacco product which also contains punk ash
    • Naswar, an Afghan tobacco product similar to dipping tobacco
    • Pituri, a nicotine-containing substance traditionally made from Australian tobacco plants, used by Indigenous Australians for chewing and placed between the lower lip and gums. They use it in high doses to induce stupor or trance.[70]
    • Snus, similar to dipping tobacco although the tobacco is placed under the upper lip and there is no need for spitting
    • Tobacco chewing gum (example, Big League Chew), a kind of chewing gum containing tobacco
    • Toombak and shammah, preparations found in North Africa, East Africa, and the Arabian peninsula
  • Topical:

Toxicity and harm potential

Graphic from the 2016 Centers for Disease Control and Prevention report entitled Smokeless Tobacco: Health Effects. The text states, "Smokeless tobacco, like chew and dip, can cause CANCER of the MOUTH, ESOPHAGUS, AND PANCREAS."
Graphic from the 2016 Centers for Disease Control and Prevention report entitled Smokeless Tobacco: Health Effects[71]
A can of Copenhagen dipping tobacco with a warning label

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.[72]

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.

In some people, it can take as little as one or two cigarettes before reaching 100% tolerance. This means a decreased dizziness from smoking. Nicotine leaves the system very rapidly. The half-life of nicotine in the brain is about 90 minutes. In 8 or 9 hours, the brain has cleared the active drug completely.[73]

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.

  • Australia: From 1 October 2021, Nicotine in salt or freebase forms (including solutions) are illegal to import into the country without a license and permit. This also includes refillable nicotine pods and any vape products containing nicotine.[74]
  • Bhutan: Tobacco products are legal, but their public use is restricted to specific smoke-friendly areas.[75]


See also

External links

References

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  2. "List of Classifications – IARC Monographs on the Identification of Carcinogenic Hazards to Humans". monographs.iarc.fr. Retrieved 2020-07-22. 
  3. Sanner T, Grimsrud TK (2015-08-31). "Nicotine: Carcinogenicity and Effects on Response to Cancer Treatment - A Review". Frontiers in Oncology. 5: 196. doi:10.3389/fonc.2015.00196Freely accessible. PMC 4553893Freely accessible. PMID 26380225. 
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  17. Addressing common myths about vaping (PDF) 
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