A is for Arsenic (23 page)

Nicotine can be absorbed through the skin, the lungs and the gastrointestinal tract, hence the wide variety of tobacco products that can be smoked, chewed, inhaled or attached to the skin (it is nicotine itself that is incorporated into patches, gum and e-cigarettes as the key ingredient used to help break the addiction to smoking).

Tobacco has been smoked, chewed and snorted for hundreds if not thousands of years in the Americas, and was first brought to Europe in 1528 by returning Spaniards. It was immediately popular; by as early as 1533, there is mention of a tobacco merchant trading in Lisbon. Both nicotine and
Nicotiana
derive their names from Jean Nicot (1530–1600), a French ambassador to Spain. In 1559 Nicot introduced tobacco to France, when he sent some seeds and dried leaves to the French royal court, along with information about the medicinal properties they were thought to possess. Tobacco became instantly popular with the royal family, and particularly with Catherine de' Medici, the Queen Mother. Fashionable members of Parisian society – always keen to imitate royalty – started using tobacco, and Nicot became a celebrity.

Dried tobacco contains between 0.6 and 3 per cent nicotine. Very little of this (around 1–2mg per cigarette) makes it into the bloodstream when cigarettes are smoked, because most of the nicotine is burnt. Consequently, the average smoker is highly unlikely to be exposed to toxic levels of nicotine. Smokeless tobacco products such as snuff or chewing tobacco have been shown to generate higher nicotine levels in the blood. The rate of absorption is slower with smokeless tobacco but more nicotine is available (because it is not being burnt), and therefore more nicotine will be absorbed. The nicotine released by chewing tobacco increases salivation, which is part of the reason why it was once popular with baseball players, as it kept the mouth moist while they were out on the dusty baseball field. Unwanted juices are spat out, but accidental swallowing has been known to give a fatal dose of nicotine.

Those working with tobacco plants or involved in harvesting or processing the leaves of the plant are at significant risk from
absorbing nicotine through their skin; this gives rise to a condition called green tobacco sickness. This affects up to 89 per cent of tobacco harvesters over the course of a season. Nicotine is highly soluble in water so workers picking tobacco leaves when it is raining, or when the plants are covered in morning dew, can absorb nicotine through their hands. Clothes may not offer any protection if they are not waterproof. Sufferers may feel nauseous, dizzy or develop a headache. There may also be increased sweating, salivation and difficulty breathing. The effects usually wear off after a couple of days, but in severe cases there can be fluctuations in blood pressure and heart rate that may require emergency medical treatment. The symptoms seem to be less severe in workers who smoke, as their bodies have adapted to the presence of low levels of nicotine.

Children are more susceptible to nicotine poisoning than adults, owing to their lower body mass. There have been several cases of nicotine poisoning in children who have eaten a cigarette end; there have also been accidents with nicotine gum, nicotine patches and e-cigarettes. There has even been a case of severe nicotine poisoning from a traditional remedy for treating eczema. A Bengali remedy used tobacco leaves, coffee and lime powder, as well as prayers, to cure skin conditions such as eczema, ringworm and scabies. However, the broken skin on the child's arms, caused by the eczema, probably allowed the rate of absorption of nicotine to rise, and after just 30 minutes the child started to feel unwell (fortunately a full recovery was made).

The poisonous properties of nicotine have been known for almost as long as Europeans have been smoking it. Toxic effects are not restricted to humans: nicotine is poisonous to anything with a nervous system, hence its use as an insecticide since at least the sixteenth century. Huge quantities of nicotine were used as insecticides in the 1940s, because it was readily available as a by-product of the tobacco industry. Nicotine can be considered a ‘green' insecticide for use on organic crops, because it is a natural substance. However, it is clear from
accidental poisonings that this was a very dangerous product. Nicotine
can
look very much like whisky, and some gardeners have unwisely stored their insecticides in old whisky or cognac bottles. Fatal mistakes have been made when gardeners have reached for a bottle of booze and taken a swig of the wrong liquid. Since the 1940s the amount of nicotine in insecticides has been reduced, and it's been replaced by nicotine derivatives, or other compounds less harmful to mammals. Nicotine insecticides are banned in Europe and the United States nowadays.
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How nicotine kills

Nicotine is a very fast-acting poison; it can kill in as little as four minutes. Inhaling nicotine is the quickest way to absorb it into the body. The lungs have thin membranes between the alveoli (tiny air sacs) and bloodstream that enable oxygen and carbon dioxide to be absorbed or expelled easily. This also makes it easy for nicotine to cross into the bloodstream. Nicotine from cigarettes can reach the brain in seven seconds. Absorption through the skin takes around an hour, but this varies depending on the individuals' skin as well as the form of delivery (for example, whether the nicotine is from a patch or in the dew of a tobacco plant). Absorption of nicotine that's swallowed (rather than inhaled) mostly occurs in the mouth or intestines, because the acidic environment of the stomach prevents the absorption into the bloodstream.

Nicotine targets specific sites within the body, by acting on a subset of receptors found in nerves. As described earlier (see page
here
), signals are transmitted across the gaps between two nerve cells (or between a nerve cell and a muscle cell) by chemicals called neurotransmitters. In 1900 the Cambridge
physiologist John Langley (1852–1925) discovered that receptors in the muscles that respond to the neurotransmitter acetylcholine are also stimulated by nicotine, so they were named nicotinic receptors. Nicotinic receptors are found at junctions within the central nervous system (CNS) and where nerves meet muscles; they are also found throughout the autonomic (or ‘below consciousness') system, where they increase activity in the sympathetic nervous system, responsible for the ‘fight-or-flight' response to a perceived danger. Activation of these nerves widens the pupils of the eyes, increases the heart rate and dilates blood vessels to the heart, brain and muscles.

Stimulation of the nicotinic receptors in muscles can cause the muscle to contract, which is the cause of the twitching sometimes seen in new smokers. These receptors quickly become desensitised to the presence of nicotine, so the twitching stops with continued smoking. Heavy smokers may show a tremor in the hands, though, due to the higher levels of nicotine in their bloodstream. The body of a regular smoker will also adapt to the presence of nicotine by metabolising and excreting it more rapidly.

Nicotinic receptors are also found in the brain, and it is the stimulation of these nerves that is the root cause of nicotine addiction. Stimulation of the part of the brain known as the ventral tegmental area (VTA) gives rise to feelings of pleasure. In an experiment, rats had electrodes placed in their VTA, and were allowed to press a lever that triggered a current in them. The rats kept on pressing the lever to enjoy the pleasurable effects. Some rats kept on pressing the lever at the expense of eating and sleeping, and had to be physically removed from it to prevent them from dying of exhaustion. Chemicals produced in the brain, such as dopamine, naturally stimulate the VTA; therefore chemicals that make dopamine more available to the nerve cells of the VTA tend to be addictive. For example, cocaine stops cells retrieving dopamine after it has been released, so the dopamine is outside the cell for longer and available to interact with receptors. In the presence of nicotine,
cells in the VTA release dopamine more readily than usual. Nicotine also reduces the amount of monoamine oxidases (MAO) in the brain to about half. MAO is a family of enzymes found throughout the body, one of which is responsible for the breakdown of dopamine. With less MAO present there is more dopamine around to interact with receptors in the VTA.

Receptors in the brain are more sensitive to nicotine than those in the rest of the body. However, a tolerance slowly builds up, and ever-increasing amounts of nicotine have to be obtained to yield the same levels of stimulation. Animals have been shown to become addicted to pure nicotine, so it is nicotine, rather than one of the other 3,000 chemical compounds found in cigarette smoke that is responsible for causing addiction. ‘Addiction' is a difficult concept to quantify; scientists have looked at the physical effects of the drug in the body, as well as the consequences of withdrawal and the desire for another ‘hit'. Although the physiological effects on the brain can be measured, there are many factors that contribute to addiction, both social and habitual. Cocaine and nicotine have been shown to have similar effects on the brain, but the experience of smoking is less pleasant than taking cocaine, suggesting that the addictive quality of nicotine is actually greater. However, some researchers comparing nicotine to cocaine concluded that nicotine was actually less addictive. What is not in any doubt is that cocaine and nicotine are both highly addictive substances.

Sufferers of Alzheimer's disease have fewer nicotinic receptors in their brain, which is thought to impair learning, reasoning and memory. Research has been undertaken into the use of nicotine patches to improve cognition in people with Alzheimer's. Smokers sometimes claim that smoking can increase attention, concentration and memory, and to a certain extent this is true. However, the raft of other harmful chemicals produced in cigarette smoke means smoking is a dangerous means of
improving academic performance. Nicotine patches are perhaps a safer alternative but before you stock up on nicotine patches or bulk-buy nicotine gum for an exam, remember to check the dosage.
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People have attempted suicide with nicotine patches, and several of them have required hospital treatment. An additional factor to consider is that the skin acts as a reservoir for nicotine, and it can continue to release it into the bloodstream hours after the patches have been removed. Serious poisoning incidents have occurred from the combined use of tobacco, nicotine gum and nicotine patches.

Another potential medical application of nicotine is for patients with schizophrenia. Schizophrenics are far likelier to smoke than other people, though the reason for this is not completely clear. It has been suggested that nicotine in the cigarettes helps control the symptoms of the disease, and schizophrenics who smoke are, in a way, self-medicating. Some schizophrenic-like symptoms can be induced in laboratory animals using drugs such as amphetamines. Activating nicotinic receptors in the brains of these animals has been shown to counteract some of the symptoms.

There can be serious side effects from non-fatal doses of pure nicotine. Harmful effects on the heart, blood pressure and muscles mean that nicotine is a somewhat risky treatment for both Alzheimer's patients and schizophrenics. Hopefully drugs will be developed that will interact preferentially with receptors in the brain, thereby reducing the side effects caused by nicotine acting on receptors in other parts of the body.

Nicotine has a dual effect, acting as both a stimulant and a depressant, depending on the dose. At low doses it is a stimulant; it stimulates the nicotinic receptors, causing nausea and
vomiting, dizziness, headache, diarrhoea, an elevated heart rate (or tachycardia), an increase in blood pressure and sweating. Activation of nicotinic receptors in the brain causes an initial stimulation, alertness, a decrease in irritability or aggression, and a reduction of anxiety.

At high doses, nicotine becomes a depressant (with pain-relieving properties). There is an initial burning sensation in the mouth, throat and stomach, followed by a rapid progression to the symptoms seen in smaller doses. There may be convulsions, respiratory slowing, cardiac irregularities and coma. Death occurs up to four hours later (sometimes much more rapidly), and is due to paralysis of the respiratory muscles. If the patient survives for longer than four hours they will usually make a full recovery.