Introduction

The health effects of cigarettes are well known -- tobacco use accounts for more than 7 million deaths each year, and smoking is the leading cause of cancer [1]. But is nicotine to blame?

Nicotine is a naturally occurring alkaloid and is only one of over 7,000 chemicals found in cigarettes. Growing evidence suggests that nicotine is responsible for only a small number of adverse health effects of smoking. In fact, this natural chemical - also found in tomatoes, eggplants, and potatoes - may give health benefits when given in small doses and slowly released into the body.

The effects of nicotine kick in when it binds to nicotinic acetylcholine receptors (nAChR). These receptors are found throughout the body but are concentrated in the nervous systems, brain, and muscles. Once activated, they set off a chain reaction of hormones and neurotransmitters that cause the physical and psychological effects of nicotine. Some of these effects are linked to the “reward pathways” of the brain, involving neurotransmitters such as dopamine and feelings of pleasure; others involve the immune system, pain responses, and inflammation.

The effects of nicotine depends on the dose, delivery system, and duration of exposure. Most importantly, the rate of absorption has been linked to the intensity of nicotine’s addictive qualities [5] [6]. One way to control the speed of delivery is to alter how it is absorbed into the body:

Smoking

Inhaled nicotine is absorbed quickly through lungs and passes into the bloodstream where it is immediately pumped through circulation and into the brain. This rapid absorption causes a “rush” and reinforces the effects of the drug on the brain [2]. Total absorption takes about 10 - 20 seconds after inhalation, but the rush can happen within seconds. It’s no secret that cigarettes are deliberately engineered with ingredients that boost the addictive qualities of smoking tobacco, and this, in combination with the “rush”, promotes addiction [2].

Gum

Chewing nicotine gum releases a set amount of nicotine into the saliva. The nicotine is then absorbed through mucous membranes in the soft tissue of the mouth. From there, nicotine is circulated to the liver for metabolism before being delivered to the brain. This provides a gentle release with a slower onset of effects. Studies suggest that this type of absorption may give the nicotine a less addictive quality [5] [6].

Patches

When wearing a patch, the nicotine is absorbed through the skin and passes into circulation where it is then delivered to the brain. Patches can be designed to release a certain amount of nicotine over a certain time period (e.g. 7mg per 24 hours). However, the amount actually released depends on variables that differ day-to-day and between individual bodies, such as the temperature of the environment, body heat, and the thickness of skin structures [3].

Photo by Jesse Orico / Unsplash

Immediate Effects

Once nicotine binds to the nicotinic acetylcholine receptors, it causes a chain-reaction that releases hormones and neurotransmitters throughout the body. Within seven seconds of binding, nicotine can create these effects:

  • Release of dopamine, adrenaline and noradrenaline
  • Increased heart rate
  • Lightheadedness
  • Increased saliva production
  • Increased concentration, focus, and memory
  • Feelings of satisfaction and increased sensitivity to feeling rewarded [37]

Addiction

Physical Addiction

Remember the nicotinic acetylcholine receptors (nAChR) we mentioned earlier? They play a major role in nicotine addiction. When nicotine binds to nAChR receptors, it activates the brain’s “reward pathway”. This pathway crescendos with a massive release of the feel-good neurotransmitter, dopamine -- a brain chemical that stimulates feelings of contentment, satisfaction, motivation and achievement.

Repetitive stimulation of the pathway creates more nAChR receptors. The pathway becomes dependant on nicotine, and desensitised to other forms of stimulation that used to promote dopamine release.

If the reward pathway doesn’t get a nicotine hit, dopamine is no longer released and the body goes through withdrawal symptoms, “begging” for more dopamine. Urges and cravings for a nicotine hit can feel overwhelming. This physical feedback loop is called “nicotine dependence”. Good news -- it’s only one part of addiction, and it can be reversed. [8]

Cigarettes contain extra ingredients that inhibit the metabolism of dopamine. So while nicotine is boosting the dopamine levels, these chemicals keep it in the body for longer, causing even stronger nicotine dependency. [7]

Psychological Addiction

Studies have shown that many people have no physical nicotine dependency but are still addicted to tobacco products due to a psychological addiction [9] [10].

Psychological addictions are driven by “triggers” -- certain rituals, people, situations or environments become associated with using nicotine, and a craving kicks in every time the “trigger” occurs. These psychological cravings may feel like a physical nicotine dependency, but this kind of addiction does not alter the brain in the way that a physical addiction does [11], and it can also be managed!

The risk of addiction has been correlated to how fast nicotine is delivered to the brain. Smoking is the fastest and riskiest, followed by nicotine replacement products such as patches, gum, e-cigarettes and smokeless tobacco [5] [6].

Nicotine Addiction Can Cause:

  • Desensitisation of pleasure centres in brain and slower release of dopamine and adrenaline when not using nicotine
  • Reduced ability to relax without nicotine
  • Increased tolerance to nicotine, and possibly to other stimulants and relaxants
  • Loss of concentration without nicotine
  • Social and financial consequences [12]

Pain Relief

Nicotine is commonly used as an analgesic by people who suffer from chronic pain. Recent research suggests that nicotine may have short-lasting, acute effects on pain sensitivity [14] and that transdermal nicotine may be effectively used to reduce pain in both smokers and non-smokers [15][16].

Nicotinic acetylcholine receptors (nAChR) are found in the central and peripheral nervous systems, where they respond to the neurotransmitter, acetylcholine, and drugs like nicotine. As well as the reward pathway, the nAChR receptors located in the nervous system are involved in pathways that control pain -- particularly chronic and long-term pain conditions [13].

When given alone, nicotine may be able inhibit pain signals by activating particular nicotinic acetylcholine receptors in the brain and the spinal cord [17]. Given in combination with alcohol, nicotine may promote the release of opioids in the body, leading to stronger pain relief and highly addictive state [36].

Nicotine may also promote short-term relief of pain due to its effects on in the immune system and inflammation pathways.

Photo by Raw Pixel / Unsplash

Effects on Inflammation & Immune System

Inflammation is a natural process that protects the body against pathogens, clears out old cells, and promotes healing. Inflammatory pathways are usually tightly regulated by the immune system but they can be altered by nutrients, chemicals and drugs including nicotine.

Nicotine is anti-inflammatory but many of the other chemicals found in cigarettes promote inflammation, as does the act of inhaling smoke. These proinflammatory agents cause irritation to tissues and cells, which triggers the immune system to release inflammation chemical messengers such as cytokines [18]. Even e-cigarette flavourings have been shown to stimulate inflammation [19]. While an acute inflammatory signal is essential for the repair and maintenance of the body’s organs and tissues, recurrent episodes from ongoing smoking can lead to chronic inflammation.

Chronic inflammation is associated with almost every health condition and can cause symptoms of constant fatigue, stiffness, body pain, insomnia, mood issues, and more. Long-term chronic inflammation can lead to permanent physical changes to organs, arteries and the brain [28].

However, nicotine is anti-inflammatory. It does this by suppressing the two main branches of the immune system -- the innate and the adaptive immune systems. Nicotine alters the development of white blood cells, and stops their expression of pro-inflammatory cytokines [20].

By reducing inflammation, nicotine may relieve the symptoms of chronic inflammation, at least in the short-term.

Some studies have shown that slow-release, low dose nicotine could provide temporary relief in complex health conditions that are driven by underlying inflammatory processes, such as:

  • Ulcerative colitis [21]
  • Depression [22]
  • Parkinson’s disease and (in some cases) Alzheimer’s disease [23]
  • Gilles de la Tourette's [24]
  • Multiple sclerosis [25]

Current research suggests that the onset, progression or symptoms of these conditions may be caused in part by an interplay between the immune system and localised inflammation [44 - 48]. Nicotine may help to relieve these symptoms, at least temporarily, by suppressing the immune system and inflammation pathways.

NOTE: Long-term immunosuppression leaves the body open to infection, and can cause serious exacerbation of chronic conditions. Seek advice from your healthcare practitioner before taking nicotine for health conditions.  

Allergies

Allergies are caused by an altered immune response, where immune cells are hypersensitive to the presence of foreign proteins. When exposed to allergens from pollen, grasses, pet hair, and food particles, the immune system sounds an alarm and tries to attack the “invader”.

Here’s a quick review:

There are two main branches of immune responses -- Th1 and Th2. During an allergic response, Th2 is dominant and causes an over-reaction to the presence of antigens. The first cells to recognise the foreign substance release IgE antibodies -- these are proteins that activate an army of immune cells. Troops of mast cells and goblet cells then release chemicals such as histamine, interleukins, and mucins. The body responds to these chemicals by secreting mucus, triggering reflexes (like sneezing), and promoting inflammation -- these processes are designed to contain and eliminate pathogens, but are excessive in cases of allergies.

Nicotine can suppress the immune system and reduce the severity of this Th2-driven immune response. Smokers are less likely to develop allergic diseases due to the effects of nicotine on the immune response and a meta-analysis of over 231,020 participants suggested that smoking nicotine could lower the risk of hayfever [26]. The same study also found a downside -- smoking could increase the risk of asthma, but correlation is unknown for other nicotine delivery methods such as patches or gum.

A 2009 study found that nicotine modulates the allergic response by suppressing Th2 cells and reducing IgE activity, decreasing histamine release and mucus concentration in airways [27]. This could mean that nicotine may lead to less hayfever, congestion, sneezing and itchy eyes; milder asthma; and less frequent eczema flare-ups. The study emphasised that while nicotine may reduce allergic asthma, the irritation from smoking outweighs the benefits and the net outcome is unlikely to be positive. However, other delivery methods may give the benefits of nicotine without the irritation.

Cancer -- Or Not!

Smoking is the number one cause of cancer worldwide, and over 60 of the compounds found within cigarettes are known carcinogens - but nicotine isn’t one of them. The metabolism of nicotine itself may form a known carcinogen:

Nicotine interacts with nitrates, bacteria, and stomach acid to form carcinogenic compounds N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). While gum users have been shown to have relatively high levels of NNNs, the amount is far lower than the amount found in cigarettes [39][40].

While NNNs may be carcinogenic, it’s unclear whether the lower levels found in nicotine gums and patches is enough to lead to cancer. One study found a level of 0.002ug NNNs in each gram of nicotine gum, versus 2.9ug of NNNs in each gram of conventional cigarette. Plus, other cancer-causing nitrosamines found in cigarettes were undetectable in the gum [49].

A review of longitudinal studies suggested no correlation between the use of snus (a Swedish smokeless tobacco product) and pancreatic cancer, lung cancer, or respiratory disease [41]. A panel of experts estimated a 90% reduction of risk of cancer from using a smokeless tobacco product rather than smoking cigarettes [40] -- and these smokeless products deliver far higher levels of nicotine compared to gum. A determination study compared blood plasma levels of nicotine after participants used various nicotine products. The research found that loose snus increased nicotine levels to 27.1mg, while chewing nicotine gum led to a much lower level 4.2mg of nicotine in the blood plasma [43]!

Cardiovascular Effects

Cigarette smoking is the greatest cause of heart attacks, stroke, and death from any cardiovascular disease (CVD). Nicotine may contribute to this risk by boosting total cardiac output, increasing pulse, contracting blood vessels and restricting circulation -- and it may increase LDL (“bad”) cholesterol levels [28]. The dose of nicotine required to cause these serious effects is easily obtained by smoking cigarettes, while nicotine replacement products may not promote these effects due to their lower dosages and slower release [29] [30].

Other chemicals found in cigarettes are responsible for cardiovascular damage associated with smoking. They can cause a thickening of the blood and increased risk of clotting, stroke and heart attack -- risks that are rarely seen in people using nicotine patches or gum [28]. In fact, a 2014 study on snus suggested that nicotine use had no correlation to incidence of stroke [42], and an early meta-analysis of over 3,700 patients showed that cardiovascular events were significantly rare in long-term use of nicotine replacement products [29].

There’s even better news -- recent studies have shown that lower doses of nicotine could benefit cardiovascular health by promoting blood vessel integrity and reducing inflammation, and may even help to repair damaged arterial tissue [31].

Second-Hand Effects

Smoking cigarettes affects everyone within a 1 metre radius of the smoker, and the subsequent chemicals can linger in the environment for years. Second-hand smoking, or “passive” smoking is deadly. Each year, over 890,000 deaths are caused by inhalation of second-hand tobacco smoke by nonsmokers [32].

Children are particularly at risk of the serious effects of secondhand cigarette smoke  and its residue which can collect on floors, blankets, and carpets in the home or car. Exposure to cigarette smoke and residue has been linked to childhood asthma, susceptibility to infectious diseases, cardiovascular issues, middle ear disease and behavioural disorders [33] [34] [35].

Some of the 7,000 damaging chemicals found in cigarette smoke include arsenic, hydrogen cyanide, and ammonia. Meanwhile, only trace amounts of nicotine are found in second-hand cigarette smoke - less than 1% of what the smoker inhales directly from the cigarette. While there are no safe levels of exposure to second-hand tobacco smoke, other methods of nicotine delivery may reduce the harm caused to others.

Nicotine has been given a bad name for its association with cigarettes, but the health effects of this natural chemical are not synonymous with all the risks of using tobacco. Taking nicotine on its own is far less dangerous than smoking -- in fact, nicotine could have therapeutic value in chronic conditions, reducing inflammation, regulating the immune system, and relieving pain. Speak to a qualified healthcare practitioner for personalised advice before using nicotine.

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