Maxfacts

Nicotine

Nicotine is a small organic molecule that can transgress the blood-brain barrier.

In the brain, the nicotine molecules bind to a specific type of receptor sites, the nicotinic acetylcholine receptors and induce a cascade of biochemical reactions that ultimately cause the release of the neurotransmitter dopamine and a few other chemicals (e.g. serotonin and beta-endorphin). Neurotransmitters are chemicals that communicate information from one neuron to another in the brain, enabling the brain to control body functions. Dopamine is involved in several such information pathways of the brain, particularly with a system known as the reward-motivated behaviour. Most pleasurable reward reactions are related to increased dopamine release in the brain and nearly all addictive substances have the effect of increasing dopamine release in the brain.

Nicotine is probably one of the best researched and investigated addictive drugs, and yet there remain many questions about its biochemical and physiological roles, especially about its psychoactive actions. Some of the difficulties with disentangling these effects originate in the combined effects of nicotine and its different modes of intake. For example, when smoking tobacco another chemical, acetaldehyde, is ingested from the smoke. Acetaldehyde is thought to inhibit enzymes that break down dopamine, thus perpetuating its ‘reward effects’. Nicotine has some other strange properties as far as addictive substances are concerned: at low dose it acts as a stimulant whereas at high dose it is a sedative (this behaviour may be related to serotonin release).

Not only is nicotine an addictive substance, it also leads to an effect known as tolerance. Regular consumption causes the nicotinic acetylcholine receptors to become saturated (entirely occupied by nicotine molecules). Consequently, the blocked receptors cannot respond anymore to their normal substrate. The body attempts to compensate for this by so-called neuroadaptation, which involves the production of more receptors. Cravings occur during periods of abstinence when more receptors become sensitive again and cravings are only relieved when more nicotine is absorbed and binds to the receptors. Tolerance mechanisms are the most likely explanation why for most nicotine consumers attempts at reducing the intake fail.

In addition to a pleasurable ‘reward’ for nicotine consumption from dopamine release, other receptors create effects that cause the typical nicotine withdrawal symptoms. For example, corticotrophin-releasing factor (CRF) is a hormone that binds to its receptor (CRF1) to mediate responses to stress. CRF release occurs at elevated levels when abstaining from nicotine, resulting in increased anxiety. Both stress and anxiety are difficult obstacles to overcome when trying to stop using nicotine. Nicotine withdrawal systems do diminish over time.

Apart from its addictive power and some adverse effects on the cardiovascular and digestive systems, nicotine ingested at modest levels is not thought to be particularly harmful (except for its adverse effects on the development of a foetus). That is the underlying reasoning for smoke-less nicotine replacement therapies, one of many different approaches and attempts to supporting smokers who try to kick the habit: nicotine provision is made for cravings by delivery by, for example, release through skin patches while avoiding the harmful effects of smoking.

Tobacco

The most common way to use nicotine is via some preparation of tobacco leaves. Besides nicotine, tobacco leaves contain a multitude of other chemical compounds that are consumed alongside nicotine. Some of these compounds are harmful. For example, some tobacco preparations contain (low concentrations of) nitrosamines, a type of chemical that is carcinogenic. Processed tobacco leaves are consumed in many ways, as snuff (continental Europe), chewing tobacco, dipping tobacco (North America), snus (Scandinavia) and most commonly: smoking in the form of cigarettes, cigars, cigarillos, in a pipe, in a shisha / hookah / waterpipe (Middle East and Indian subcontinent). A smokeless way to inhale nicotine is the more recent method of vaping (electronic cigarettes) where a liquid mixture of water, nicotine, some glycerine and flavouring are heated and the resulting vapour is inhaled.

Snuff is a traditional, smoke-less way to consume tobacco / nicotine, common all over the world. Snuff uses pulverised, fermented tobacco leaves. The preparations range from very fine, dry powders to slightly coarser textures which usually are moister. Many snuff preparations are flavoured (menthol, amongst many other flavourings), many are matured for extended periods and there are many traditionally established local varieties and flavours. A traditional Bavarian, powerful version of snuff is called ‘Schmalzler’ because it used to be refined with clarified butter (Butterschmalz). The Bavarians also invented supersized, colourful handkerchiefs for the discerning snuff user – big enough to cope with major sneezing attacks following a good ‘snuffing’, but equally suitable to cover the (bald) head as a sun protection in summer or to double up as a scarf in winter.

Snuff is, - snuffed: a pinch of the material is snuffed up from the back of the hand into the nose, which takes a little bit of practice. Uptake through the nasal mucosa provides a shortcut for nicotine to the brain where it is delivered within seconds. Snuffing is usually immediately followed by a mighty sneeze. Snuff is considered a slightly less harmful way of consuming tobacco because it avoids the harmful effects of smoking. Nevertheless, addiction to nicotine remains and long-term snuffing damages the nasal mucosa.

Chewing tobacco is another smoke-less way to consume tobacco / nicotine. It is prepared from fermented tobacco leaves that are either cut into strips (like pipe tobacco), or more finely cut and pressed into plugs or pellets. These require chewing to release flavour and nicotine. This form of tobacco / nicotine consumption seems to have fallen out of fashion of late.

Snus (traditional in Scandinavia, especially Sweden) and dipping tobacco (traditional in North America) are two similar varieties of moist pastes made from milled tobacco leaves. These preparations use tobacco preparations that are less, or not at all, fermented than typical tobacco preparations for snuff or smoking tobaccos. Some snus preparations are flavoured and there are fortified snus versions with enhanced nicotine content. Snus is normally packed in small pouches that are placed between lip and gum for long periods of time. Nicotine is then continually released and taken up via the oral mucosa. Continued oral consumption of tobacco preparations in chewing tobacco, snus or dipping tobacco have all been shown to lead to periodontal disease (gum disease) and other lesions of the oral mucosa. It is thought that increased risks of oral, oesophageal and pancreatic cancers are related to oral smoke-less tobacco / nicotine consumption.

Smoking tobacco in some way is by far the most common form of nicotine consumption worldwide. It is also the most harmful form of nicotine consumption and has been identified as the ‘biggest avoidable cause of death on the planet’.

In addition to the addictive properties of nicotine, inhaling the smoke from combusting fermented & dried tobacco leaves is seriously harmful. Of the known ca. 4000 different chemicals in tobacco smoke, at least ca. 100 are known to be carcinogens. Many of these are contained in the tar that is formed by incomplete combustion and inhaled. Other substances in the inhaled smoke are simply toxic, for example heavy metal ions (lead and arsenic), or carbon monoxide and hydrogen cyanide. Continued exposure to smoke, especially accumulation of the tar components, damages the lining of the windpipe and lungs (the respiratory epithelium). It harms the motile cilia, surface structures of cells that are normally responsible for clearing dirt and mucus from the lungs (smoker’s cough).

Inhaling tobacco smoke has been shown to cause lung cancers and other incurable lung conditions, to increase the risk for head and neck malignancies, to cause damage to the cardiovascular system and to increase the risk of coronary artery disease, stroke and heart failure. Very recently, an extended mapping of genetic fingerprints has identified multiple mutational genetic signatures of human cancers associated with tobacco smoking, including head and neck cancers.

Perhaps some extra-motivation to quit smoking when confronted with oral and maxillofacial surgery: if the above list of proven general adverse effects of tobacco smoking does not provide sufficient motivation to try and give up, perhaps the following facts are worth to ‘think about’ when faced with major surgery. Tobacco smoke acts as a vasoconstrictor (narrowing of blood vessels) and thus reduces blood supply to tissues. Short term, this has negative effects on wound healing, which in turn increases the risk of infections. The post-operative thrombosis risk is significantly higher for smokers (not just deep vein thrombosis but also blockage of blood vessels at surgical sites). Bone and/or soft tissue grafts and flaps have a significantly higher risk of failure for smokers. Continued tobacco smoking significantly reduces the chances of success of radiotherapy: reduced oxygen-levels make tumour cells less susceptible to destruction by high-energy photons. Long term, continued exposure to tobacco smoke increases the risk of recurrence of malignancies, and/or the occurrence of new malignancies.