Tobacco and nicotine Flashcards
Tobacco plants
Tobacco plants are another subfamily of the Solanaceae family.
They originate in Central and South America and spread through both continents
There are ~70 species including Nicotiana rustica and Nicotiana tabacum.
Nicotine is common across many nightshade plants. It is derived from ornithine decarboxylation to putrescine.
Nicotina species lack the tropane alkaloids found in deadly nightshade.
There is a difference in the capacity of different species to generate nicotine. N. rustica has <9% nicotine, while N. tabacum has <3%.
Tobacco in the Ancient World
There is evidence from 8000 years ago for tobacco use by indigenous people in Central and South America.
Use continued in the Mayan and Aztec civilizations, mostly using pipes. This use was almost exclusively male.
Tobacco was used occasionally rather than daily.
In some communities, N. tabacum leaves were rolled into a conical shape and smoked or chewed for mystical/ceremonial purposes. These were called ‘tobags/tabags’ or ‘tobacos’.
Australia also has indigenous tobacco species. The indigenous population chewed the leaves.
Tobacco and Colonisation of the Americas
In 1492, Columbus noted the consumption of tobacco when arriving in Cuba.
In the 1520s, returning Spanish occupiers brought tobacco back with them.
In 1531 Spanish settlers started growing tobacco on plantations in Santo Domingo.
In 1559 samples were sent to Paris. This included seeds and leaves, with a recommendation for King Francis II to use it as snuff.
In 1570s tobacco seeds were brought to England. There was a popularization of pipe smoking in Elizabeth I’s court by Walter Raleigh.
Missionaries to the Americas took up the habit. There was a ‘greater conversion to tobacco than the indigenous population took to Christianity’.
There was some pushback to the popularisation of tobacco. In 1590 the Pope forbade the clergy from smoking during mass on pain of excommunication. In 1604 King James I of England wrote a pamphlet called ‘Counterblast to Tobacco’.
In 1612 Nicotiana tabacum from Brazil was introduced to Virginia as a crop.
In 1614 the first crop was sent to England, but the tobacco produced may not be as good as the weather is not as suitable for its cultivation.
In 1618 King James I executed Walter Raleigh and in 1621 he banned tobacco farming in England (but protected Virginian and Bermudan production). Mid-1620s, tobacco was the primary trade with England.
Tobacco and the Transatlantic trade
From 1638, Virginian tobacco flooded western Europe. In 1639, 750 tons were shipped to England and in the 1660s tobacco was promoted to protect against the Great Plague of London.
By the end of the 1600s, 10k tons.year were shipped from the colonies to England, and this reached 250k tons/year by the end of the 1700s.
American indigenous populations were insufficient for labour demands. There was then a massive expansion of the importation of African slaves, so the tobacco trade fuelled the industrial scale of slavery.
Tobacco farmers, including George Washington and Thomas Jefferson, incurred sizable loans from London - imposition of tariffs meant that they were indebted to London.
In the 1750s tobacco prices fell.
In 1775 the American ‘Revolutionary War’ started. There is an argument that the increase in tariffs on tobacco with the concurrent enforcement of decreased prices were a main driver for the separation of the US from the British empire.
Tobacco consumption in US and Europe
There were widespread bans of smoking in various locations.
In 1840, Prussia banned smoking in public places.
In 1847 Philip Morris started the sale of hand-rolled Turkish cigarettes in the UK.
In 1854-6 veterans of the Crimean War bring back cigarettes
In 1890, 15 US states ban the sales of cigarettes
In 1914-18, WWI caused a huge increase in ‘soldier’s smokes’
In 1933 Hitler came to power in Germany and the Nazis started an anti-smoking campaign. Cigarettes were used as a form of currency
In 1941 there was then a ban on public tobacco consumption in Germany. Still, 1939-45 was a peak time of cigarette consumption.
In 1952, cancer-causing chemicals, particularly tar, were identified in tobacco.
Early use of nicotine
In the late 1600s, N. tabacum extract was used as an insecticide.
In 1745, Richard Meade and others recommended tobacco smoke enemas as a treatment for drowning. This was apparently based on usage in north American populations following the idea that you can warm people from the inside as a treatment.
In the 1780s, the Royal Humane Society install resuscitation kits, including tobacco enemas, along the River Thames.
In 1835 there was a report of the ‘successful’ use of tobacco enema to treat cholera.
In 1828 Posselt and Reimann (Germany) isolated nicotine from the tobacco plant.
Cycle of tobacco/nicotine use
The first use of tobacco causes a balance of aversion and reinforcement.
Repeated use causes induced plasticity and reduces aversion. Aversive effects decrease and there is an amplification of reinforcement.
Paraphernalia refers to reinforcement condition cues. A collection of items or equipment associated with an activity like smoking, such as being exposed to ashtrays, other smokers, or environments where you are used to smoking, such as bars, can induce cravings.
Abstinence prompts withdrawal symptoms, including craving, prompting relapse.
There is a balance between aversion and reinforcement with nicotine use, which is different from the mechanism of other drugs of abuse.
Molecular targets of nicotine
Nicotine causes direct activation of nicotinic acetylcholine receptors. These are pentameric cys-loop ligand-gated Na+ channels.
there are 16 subunits in mammals: ɑ1-10, ꞵ1-4, 𝛾, δ, ε.
Nicotine acts as an agonist at nicotinic receptor subunits, except at ɑ9-ɑ10 subunits, where it acts as an antagonist. This antagonism is possibly involved in the mild analgesic action of nicotine.
Acutely, nicotine increases VTA-NAc dopamine release by activating ɑ4ꞵ2 subunits. This pathway is involved in reward and reinforcement.
Nicotine regulates the medial habenula/interpeduncular nucleus pathway by activating ɑ3ɑ5ꞵ4 subunits. These regions are involved in the regulation of monoamine release, particularly dopamine.
At nicotine concentrations found in human smokers, ꞵ2 subunits rapidly desensitise, while ɑ7 subunits desensitise slowly.
Following long-term smoking, ɑ4ꞵ2 subunits are upregulated in the cerebral cortex and ꞵ3ꞵ4 subunits are upregulated in the medial habenula/interpeduncular nucleus.
Nicotine stimulates nAChR in sympathetic ganglia to increase neuronal noradrenaline release and adrenaline release from the adrenal glands.
Moderate doses increase HR and BP, particularly in naive users, due to peripheral vasoconstriction.
Higher doses lead to ganglionic blockade, causing hypertension and circulatory collapse.
Metabolism
Nicotine is metabolised in the liver by CYP2A6.
Following long-term use, activation of the aryl hydrocarbon receptor leads to induction of CYP1A2.
This has implications for metabolism of other drugs, as they would be metabolised faster. There is a reduced plasma concentration for caffeine, theophylline, haloperidol, propranolol, etc.
Statistics
In 2019 it was estimated that ~1.14 billion people smoked.
There was 1 smoking-related death for every 0.8-1.1 m cigarettes.
There is a high cigarette consumption in China, Russia and America, but population density should also be considered - a large proportion of Eastern Europeans smoke but the population may not be as high due to low density.
There are some differences in tobacco consumption between males and females, particularly in Africa where there is stigma and discrimination against women smoking.
Looking at nicotine-related mortality, there is a high rate in Russia, south-east Asia and Denmark.
Global death caused by different forms of tobacco exposure show that smoking causes the most, second-hand smoke next and chewing tobacco causes negligible amounts.
The Health Survey for England shows that the number of smokers has decreased, as has the average number of cigarettes smoked per day.
Cigarette smokers have a hard time quitting. There is an increase in quitters, but a lot of support is required, both in terms of pharmacotherapy and behavioural support.
The number of people who have never smoked is increasing.
However, for smokers, many individuals have their first cigarette less than two hours after waking up (>70%), with more than 10% having it within less than 5 minutes!
There is less tar associated with vaping, so there may be less long-term damage, but this does not take into account the fact that there are other chemicals present in vapes.
18-24 year olds use a disproportionate amount of e-cigarettes compared to other age groups – people are starting to use vapes without having smoked cigarettes first, so they are not trying to quit.
*Arecoline
Arecoline is a naturally occurring psychoactive alkaloid from areca nuts of the areca palm (Areca catechu) native to South and Southeast Asia.
The abuse of areca nuts is widespread, with >600 million users globally. It’s the world’s fourth most commonly used human psychoactive substance after alcohol, nicotine, and caffeine.
Chewing areca nuts dates back millennia and is culturally significant in some Asian nations. Its use has spread globally through migration and commercial products, often combined with betel leaves and slaked lime to form “betel quid”.
Arecoline has a long history in traditional medicine, used for its antihelmintic, aphrodisiac, and painkilling properties. Areca nut consumption remains predominantly an Asian phenomenon, with India being the major producer.
The areca nut contains various alkaloids, with arecoline being the key, biologically active one, making up 0.3-0.6% of the nut.
It is a partial agonist of nicotinic and muscarinic acetylcholine receptors in the CNS, causing effects including stimulation, alertness, elation, and anxiolysis, similar to nicotine, and can also lead to addiction and withdrawal symptoms.
Arecaidine, a metabolite of arecoline, inhibits GABA and beta-alanine uptake.
Depending on the dose, arecoline can produce cognition-enhancing, psychostimulant, euphoric, pro-arousal, aphrodisiac, anxiolytic, and sedative effects.
Peripheral effects include hypersalivation, hypotension, vertigo, and altered heart rate.
In the oral cavity, arecoline can form carcinogenic N-nitrosamines, leading to its classification as a Group 1 carcinogen.
Arecoline has a long history in traditional medicine in Asia, used for its antihelmintic, aphrodisiac, and painkilling properties. Areca nut consumption remains predominantly an Asian phenomenon, with India being the major producer.
