What happens to your body when you take in nicotine?
This morning, many people in the UK will have begun their day by consuming two naturally occurring chemicals; namely the caffeine in their morning cuppa, and nicotine. Prior to about 2008, the vehicle for nicotine delivery for virtually all of these people would have been combustible tobacco, i.e., cigarettes. But then there was a consumer-led public health insurgency in the form of e-cigarettes, with empowered smokers accessing an alternative vehicle for nicotine delivery, one far less harmful than combustible cigarettes.
Both smoking and vaping deliver nicotine to the user, that’s pretty much where the comparison ends. We all know that nicotine is addictive, people smoke and vape for nicotine. We all know that smoking causes cancer, but many still believe this is due to nicotine. Science tells us otherwise; nicotine does not cause cancer or indeed any smoking-related disease. The noted tobacco researcher Michael Russell perfectly articulated this in 1976, “People smoke for the nicotine but they die from the tar”.
But first, what is Nicotine?
Nicotine is a compound naturally found in the plants belonging to the Solanaceae family, of which only the tobacco sub-family contains sufficient nicotine concentrations to exert a pharmacological effect. It also presents in a variety of edible plants. In chemistry, nicotine is known as a “tertiary amine”, consisting of a pyridine and pyrrolidine ring.
Through nature, the nicotine found in tobacco is made in just one 3-dimensional structure. This is known in chemistry as an “optical isomer”, and is responsible for the effects of nicotine in the body. A very small amount of the other “optical isomer” is formed when you light a cigarette.
What happens when you light a cigarette?
When you light a cigarette, a process known as pyrolysis, nicotine is distilled from tobacco and carried in smoke particles into the lungs. Here it is rapidly absorbed into the pulmonary (lung) veins that transfer oxygenated blood from the lungs to the heart. Once entered into arterial circulation it quickly reaches the brain. Smoking is a highly efficient form of nicotine administration, as it rapidly enters the lungs and moves to the brain in seconds. As the nicotine is inhaled, it’s not digested like when you take an aspirin for a headache, and much more of the active compound reaches your circulatory system.
E-liquid is the fuel that powers your e-cig. It is a liquid that is vaporised by your device and is turned into a ‘vapour’ that you can inhale.
How does this compare to when you inhale on an e-cigarette?
When you press the button and inhale on an e-cigarette, the battery converts electrical power into heat using coil of a thin wire. The heat generated from the coil evaporates the e-liquid in a wicking material in the atomizer head.
The main base ingredients of e-liquid are propylene glycol and vegetable glycerine, with most also containing flavourings and nicotine. The heated coil temperature is sufficient to vapourise the liquid. The air drawn through the e-cigarette; by the inhaling action of the user, rapidly cool the vapour into tiny droplets. It is these nicotine-containing droplets which are carried into the lungs. Absorption of nicotine into the pulmonary (lung) veins is less rapid compared to cigarette smoke, with lower nicotine boost into the bloodstream. Again, once entered into arterial circulation it quickly reaches the brain. Remember; like smoking, vaping is an efficient way of delivering nicotine to your circulatory system without losing a lot of the active compound by metabolism through our digestive system.
Nicotine has reached the brain, now what?
This is where it gets a bit complicated, so let’s try and keep it simple. Nicotine is a stimulant in low doses and a depressant of the nervous system in high doses. When we consider nicotine delivered by cigarettes or e-cigarettes, we are talking about low doses. Nicotine activates receptors in specific parts of the brain, spinal cord and peripheral central nervous system (nerves that branch to organs/muscles). The principle receptors stimulated are called nicotinic acetylcholinergic, sorry we promised to keep this simple but you can see the similarity in the name! Activation of these receptors in the brain results in the release of neurotransmitters, the body’s chemical messengers. The important neurotransmitter released, one which you may know, is dopamine. It’s known as the “feel-good” neurotransmitter for good reasons. The brain releases it when we eat certain foods we crave or even while we have sex, contributing to feelings of pleasure and satisfaction as part of the brains reward system.
It’s ultimately more complex than simply the release of dopamine in the brain and peripheral central nervous system, with a pattern of indirect effects on other transmitter systems, but we don’t need to go into such detail.
Dopamine release in the brain, critical to the reinforcing, addictive effects of nicotine
We’ve talked about the release of dopamine when nicotine binds to receptors in the brain, and its association with pleasure. The mechanisms by which nicotine mediates the release of neurotransmitters such as dopamine are complex and beyond the scope of this article. All we need to remember is that nicotine indirectly stimulates the release of dopamine by changing the response of nicotinic acetylcholinergic receptors, this is called modulation in biochemistry. Nicotine also stimulates direct release of dopamine and further aids its release by inhibition of other so-called inhibitory neurotransmitters. If the nicotine is delivered in cigarette smoke, then chemicals present in the smoke (not nicotine) can inhibit an enzyme which is responsible for the lowering of dopamine levels in the brain. These chemicals present in cigarette smoke are not present in vapour from an e-cigarette. We’ll talk about this in a bit more detail later on.
Now we know that nicotine alters brain chemistry, so how does this affect you?
Well, your genes will play a role in your susceptibility to nicotine dependency but let’s put that aside for the moment. Nicotine induces stimulation and pleasure, reduces stress and anxiety. Smokers and vapers use nicotine to control their level of arousal and mood. It can also improve concentration, reaction time and performance of certain tasks. These effects are known as positive reinforcement and increase the brains reward function. Now for the negative reinforcement of nicotine withdrawal symptoms, such as when a person quits smoking. These include irritability, anxiety, insomnia, low mood, poor concentration, increased appetite, relationship problems and cravings. Researchers believe that a drop in dopamine levels following long-term nicotine exposure accounts for mood disorders and tobacco craving, which may persist in ex-smokers for a long time. This decrease in brain reward function experienced during nicotine abstinence is a key component of nicotine addiction. It makes nicotine, particularly in tobacco, very hard to quit.
When repeatedly exposed to nicotine some people, but not all, develop a tolerance. This is called neuroadaptation and can be accompanied by an increase of nicotine receptors in the brain. This can also play a role in addiction, as it’s believed that some of the desensitised receptors become responsive again during a period of abstinence, even during night time sleep. This can explain why a smoker craves a cigarette first thing in the morning, or why chronic smokers can experience quite severe withdrawal symptoms during a “cold turkey” quit attempt.
Role of conditioned behaviour in nicotine dependence
Nicotine-taking behaviour is learned, as the result of conditioning. The pharmacologic effects of nicotine have been discussed, but we also need to recognise that the user begins to associate moods or situations with the rewarding or negative reinforcement effects of nicotine. Learnt behaviours combined with pharmacologic action leads to dependence. This is why conditioning is a major factor in nicotine relapse after a period of cessation, and must be addressed as a component of behavioural therapy during smoking cessation counselling. This is in addition to a safer and gradually decreasing delivery of nicotine to alleviate symptoms of withdrawal (vaping and/or nicotine replacement therapy).
But is nicotine alone responsible for dependence and addiction?
Evidence suggests tobacco has additional effects beyond nicotine. Tobacco smoke consists of thousands of chemicals, whereas vapour from an e-cigarette is a few dozen chemicals, dependent on the flavour. It’s been established that cigarette smoke inhibits an enzyme called monoamine oxidase, which is responsible for the metabolism of a certain type of neurotransmitter, such as dopamine. This results in increased levels of dopamine in the brain, potentially contributing significantly to reward and dependence (addiction). Nicotine alone is not directly responsible for this effect.
Nicotine also stimulates nerves that branch to muscles and organs, how does your body respond?
Nicotine is a substance which induces a response from the sympathetic nervous system, the body’s rapid involuntary response to dangerous or stressful situations. You might know it as the fight or flight response. Heart rate increases, with a temporary increase in blood pressure and constriction of associated blood vessels. If you suffer from a pre-existing heart condition, such as coronary heart disease, you’d be concerned at this point but we need to balance this with the fact that caffeine has similar stimulatory effects. Although it’s recognised that medicinal nicotine causes temporary changes to the cardiovascular system, population studies have not found the use of nicotine to be linked to cardiovascular disease. The science is called epidemiology, we’ve sadly all heard the term in the news this year due to the COVID-19 pandemic. Clinical trials of nicotine patches in smokers with cardiovascular disease show no increased risk of cardiovascular events compared to trial participants taking a placebo. There’s also the experience of men in Sweden with a history of snus use, a smokeless tobacco product which delivers nicotine. The long-term data indicates little to none increase in cardiovascular risk. This evidence demonstrates that the method of nicotine delivery is key for evaluating risk to the cardiovascular system, with a proven relationship between smoking and increased risk of heart disease.
How does my body remove nicotine?
For regular smokers, nicotine persists in the brain throughout the day and night, the receptors in the brain change structure and function, resulting in a tolerance to nicotine. This is called neuroadaptation, and it plays a role in nicotine dependence. After a period of time, the body will start to chemically process the nicotine to remove it from your system, a process known as metabolism. Different people metabolise nicotine at different rates, with women generally metabolising nicotine quicker than men. The organ which metabolises nicotine is the liver, and this process chemically changes nicotine to other related chemical compounds (metabolites). The main metabolite of nicotine is called cotinine, and its detection is used as a test for nicotine exposure; for example, to measure compliance with treatments for smoking cessation. Five other primary metabolites of nicotine have been identified, although a detailed discussion on the metabolic pathways and excretion is beyond the scope of this article. In simple terms, the metabolites of nicotine are eliminated through your kidneys as urine.
- Nicotine has a dependence (addiction) potential, although the method of delivery plays a critical role.
- Nicotine delivered via combustible tobacco is addictive and exposes the user to thousands of chemicals in tobacco smoke, many directly linked to smoking-related disease.
- Nicotine alone does not contribute to the risk of smoking-related diseases, such as cancer or heart disease. Nicotine alters brain chemistry and stimulates the nervous system.
- When combined with smoking behavioural and sensory stimulation, dependence potential is maximised.
- Chemicals present in cigarette smoke can enhance the addictive potential of nicotine.
Is there a safer way to deliver nicotine, whilst maintaining satisfaction and gradually reducing dependence?
Vaping is a far safer way to deliver the nicotine requirements of the current or former smoker. Remember, smoking related disease is due to the thousands of chemicals in cigarette smoke, not the nicotine. Vaping offers smokers comparable behaviours, such as hand to mouth action and inhalation sensation, and also the positive reinforcements of nicotine delivery. The e-cigarette vapour delivery of nicotine has a fraction of the risk of smoking. Vaping offers smokers a highly effective means to gradually reduce and eliminate their nicotine dependence, by decreasing the nicotine strength of their e-liquid according to the stage of their smoke free journey.