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Ask the Scientist: How Does Nicotine Withdrawal Work?

3 Mins read

Smokers and vapers of nicotine-containing e-liquids will all be well-aware of that desire for your next smoke or puff of an e-cigarette and how difficult it is to cut down or quit altogether. 

So why is it so hard to quit and what effects are happening within the body? 

When someone smokes tobacco or vapes nicotine e-liquid, nicotine is rapidly absorbed into the pulmonary system facilitated by the large surface area of the lungs. From there, nicotine enters the arterial bloodstream and into the brain where it interacts with several receptors and pathways causing a physiological response. 

The first thing people will notice is that their heartrate increases. This is through the activation of the adrenal glands that release adrenaline. This leads to the constriction of blood vessels and increased heart rate and blood pressure, which can give an enhanced feeling of alertness.  

The body has numerous neurotransmitters that behave as chemical messengers which control signalling between neurons, and neurons to muscles, upon interaction with receptors.  Nicotine can mimic the neurotransmitter acetylcholine that is produced naturally in small amounts and regulated by the body. 

As nicotine mimics this neurotransmitter, it can bind to the same cholinergic receptors. This results in unregulated stimulation and activation and the body also produces more acetylcholine as a response. The activation and stimulation of cholinergic receptors leads to an increased release of dopamine that would not naturally occur.

Dopamine is involved in several physiological processes such as attention, learning and emotional responses. The release of dopamine also contributes pleasurable experiences including satisfaction and is a part of the mesolimbic pathway (also known as the reward pathway). The dysregulation of this pathway is a known major component in cases of addiction.

Nicotine also stimulates the release of several other neurotransmitters such as glutamate, hydroxybutyric acid (GABA) and endorphins which can have pain relieving effects and lead to a feeling of euphoria.

Effects of Nicotine Withdrawal 

People who use nicotine-containing products experience many things that they find pleasurable as a result of nicotine’s interaction within the body and its chemical pathways.  However, with consistent exposure to nicotine, tolerance to its effects develop rapidly from neuroadaptation. 

When this develops, the number of binding sites on cholinergic receptors and others increase from desensitisation. When tolerance has developed, these receptors become more active in periods of abstinence causing the sensation of withdrawal and craving. 

Cessation of nicotine can cause several withdrawal symptoms, such as irritability, anxiety, depressed mood and increased appetite, leading to the basis of nicotine addiction. As soon as you stop taking nicotine your body will soon start to crave it, with that longing for the next cigarette or vape occurring in as little as 2 hours. 

Symptoms of nicotine withdrawal usually occur after 4-24 hours and most often peak on the third day before diminishing over several weeks. Relapse is often the result of desire to alleviate symptoms through the administration of further nicotine. It has been demonstrated that cognitive defects occur during the process of abstinence, such as decreased attention and working memory.  

Another issue of nicotine withdrawal is the behavioural element, such as routine and other social aspects, such as lunch breaks or nights out with friends that make quitting difficult.

Going through a cold-turkey approach is often difficult due to the strength of withdrawal symptoms. It has been shown through research that nicotine replacement therapies can increase the likelihood of successful cessation.

One such approach is e-cigarettes, where the user can start off on an appropriate strength nicotine and progressively over time, decrease the nicotine strength in a tapered approach until replacement is no longer required.  

About the Author

Dr Richard Cunningham has a Ph.D in medicinal chemistry from Queen’s University Belfast where he also worked as post-doctoral researcher for a number of years before working in the US at the Mitchell Cancer Institute in Alabama. Among his areas of expertise are organic synthesis, nucleosides, nucleotides, cellular biology, vitamins, aminoglycosides, drug delivery, phosphorous chemistry and chemical analysis.

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