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Nicotine Withdrawal Symptoms, the Brain & Treatment Rationale

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The Significance of Nicotine Withdrawal Symptoms

Along with mental preoccupation and tolerance, nicotine withdrawal symptoms are the hallmark of nicotine addiction. The nicotine addictionsignificance of withdrawal symptoms lies in the fact that they are the main reason many fail to quit smoking. According to surveys, most smokers want to quit and many try. But few succeed. According to the National Health Interview Surveys of 2010, 68% of adult smokers said they wanted to stop smoking. Of that group 52.4% said they tried. Only 6.2% of that group of respondents succeeded though.

Understanding why nicotine withdrawal symptoms occur and how the medications that treat them work can promote patient engagement with doctors’ efforts to help patients quit smoking. That engagement can in turn lead to improved compliance with treatment. The end result is a greater likelihood of success with an attempt to quit smoking. 

Symptoms of Nicotine Withdrawal

Symptoms of nicotine withdrawal are the body’s reaction to not having sufficient amounts of nicotine in it. The symptoms can vary between smokers, but the typical ones are as follows:

  • anxiety
  • irritability
  • jitteriness
  • headache
  • difficulty concentrating and thinking clearly
  • difficulty sleeping
  • depressed mood
  • fatigue
  • tobacco craving
  • increased appetite with weight gain

Nicotine Effects in the Brain

The basis of nicotine addiction and symptoms of nicotine withdrawal are the effects of nicotine in the brain. The main effect is nicotine withdrawal the stimulation of the reward center in the brain. It binds to acetylcholine receptors in the ventral tegmental area of the midbrain. The binding causes the release of the neurotransmitter – dopamine. Dopamine then sends a message to the nucleus accumbens – a basal ganglion and the end point of the highway within the reward center of the brain called the mesoaccumbens pathway. It is the pathway to pleasure which all drugs of abuse trigger.

The triggering of this pathway in turn reinforces the behavior that serves as the trigger. It initially does so because of the pleasure it produces. As addiction sets in though it drives behavior to prevent or suppress symptoms of withdrawal. Eventually nicotine hijacks, so to speak, the receptors in the reward center of the brain, usurping their involvement in other life-sustaining mechanisms such as hunger, thirst and reproduction. The end result is an obsession with smoking to the point that it has priority over various aspects of the addict’s life and rational thinking.

Tolerance – the need for increasing amounts of and addictive substance to satisfy a craving – develops with the long-term use of nicotine.  The reason is up-regulation (an increase in the number) of the nicotinic cholinergic receptors in the midbrain. These receptors respond to both nicotine and acetylcholine but have a preference for nicotine.

nicotine withdrawalA craving for nicotine occurs in proportion to the number of empty receptors not occupied by nicotine. Therefore, since half of the inhaled nicotine usually leaves the body within two hours of smoking a cigarette, smokers have a frequent urge to light up. The actions of nicotine in the brain might well explain the observed inverse correlation between Parkinson’s disease and nicotine use.

The deep-seated label for nicotine addiction is not just figurative. It has literal implications. The reasons are twofold.  First, the structures of the reward center in the midbrain that drive addiction are deep in the regions of the brain below the cerebrum. Secondly, they are in the oldest parts of the brain from a phylogenetic point of view.

Why nicotine addiction is so powerful

Cigarette smoking is a very strong habit to break.  Evidence of this fact is the patient who smokes through a tracheostomy or in spite of having caused a house fire while smoking. Recovering alcoholics and drug addicts often report greater difficulty quitting smoking than the use of other substances of choice. The relative difference probably rests in the physiology of smoking.

Upon inhalation nicotine diffuses across the large surface area of the alveoli of the lungs. From there it rapidly enters into the pulmonary capillaries which convey it to the left side of the heart via the pulmonary veins. The left ventricle then pumps it to the brain where it triggers the reward pathway as discussed above. Because the process is rapid nicotine reaches the brain in less than 20 seconds after inhalation.

The speed with which inhaled nicotine reaches the brain is even faster than drugs injected through a vein. The reason is drugs injected into a vein must first pass through the right side of the heart before reaching the lungs, left side of the heart and brain in that order. With drugs taken by mouth the process is even slower because they must first pass through the liver where they undergo metabolism before then entering the right side of the heart, the lungs, the left side of the heart and the brain in that order.

Hence, the reward center receptors in the midbrain receive a faster and probably heavier hit, if you will, from inhaled nicotine, than they do from other non-inhaled substances of abuse.

Nicotine withdrawal symptoms treatment rationale

Attempts to quit smoking with strategies which rely on higher brain function at the level of the cerebrum are often doomed from the start. The reason is they don’t address the chemical nature of the problem in the lower portion of the brain and don’t deal with the symptoms of nicotine withdrawal. The most successful strategies for quitting smoking tend to be those using one or more of the methods which rely on higher brain function combined with pharmacotherapy – the treatment of disease with drugs.

Stop Smoking Medication

The Food and Drug Administration (FDA) currently approves of three types of medications for the treatment of nicotine withdrawal symptoms. They are the following:

  • Nicotine replacement therapy
  • Bupropion (Zyban and  Wellbutrin SR = brand names)
  • Varenicline (Chantix and Champix = brand names)

The rationale for nicotine replacement therapy is that the nicotine in tobacco does not cause cancer or any of the other health nicotine withdrawal symptomshazards associated with chronic tobacco use. Rather, it is some of the more than 4800 other compounds in tobacco that do. Thus, the use of nicotine replacement agents is a much safer alternative to inhaled tobacco, even if it ends up being a substitute addiction.

There are five different forms of nicotine replacement therapy. They are chewing gum, patches, lozenges, nasal spray and inhalers. The gum and lozenges don’t require a prescription. Patches are available via prescription or over-the-counter. A doctor’s prescription is required to buy the nasal spray and inhalers. According to research, a combination of a nicotine patch and gum is the most effective and inexpensive initial course of treatment.

Bupropion is an antidepressant which reduces the craving for nicotine. Its mechanism of action in battling smoking is unknown. But researchers believe it involves mild blocking of dopamine reuptake in the midbrain. Its success rate for smoking cessation is better than no treatment but less than that of combination nicotine replacement therapy or varenicline.

Varenicline is a designer drug which imitates the binding of nicotine to the cholinergic receptors in the reward center of the brain. In doing so it blocks the binding of nicotine and partially stimulates the production of dopamine. It can cause mild physical dependence. But it is not truly addictive in that it is not associated with tolerance. Studies have shown it to be as effective as the nicotine gum and patch combination for smoking cessation.

All forms of medical treatment for nicotine addiction should be under the guidance of a doctor. The foremost reason is some of the medications are not safe for some people to use. Secondly, the medications can cause side effects in some individuals. Thirdly, studies have shown that quit smoking rates tend to be greater when a doctor is involved in the management.




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