What are the physiological changes taking place during withdrawal?

The brain and the body, like humans, do not take kindly to abrupt changes in their environment. When the body is exposed to small daily changes, it gradually adjusts to those changes through a process known as adaptation. Adaptation is seen in many physiological processes and occurs both at the molecular level as well as at the behavioral level. It is the whole reason behind developing strength and endurance through daily graduated exercise. The muscles increase in size and develop more blood vessels in order to deal with the increasing demands being made on them. The heart enlarges and grows stronger. Oxygen is delivered more quickly and efficiently to those organ systems requiring it. Bones get stronger to handle their increasing loads. Adaptation also occurs in the brain through a process known as neuroplasticity[1]. An athlete who practices daily improves technically over time. This occurs as the brain adapts and "memorizes" by "rewiring" through neuroplasticity the correct coordination of muscle movements for maximum performance. This is often referred to by trainers and coaches as muscle memory. It occurs with all motor skills that are utilized daily, from learning to walk, to driving a car, to complex activities such as athletics, playing a musical instrument, or becoming a surgeon.

When you take a drug every day, adaptation occurs in response to the drug. As stated earlier, this happens with almost all drugs, regardless of whether or not they are addictive. However, for drugs regarded as potentially addictive the adaptation is termed tolerance. Tolerance is both psychological as well as physiological. When a drug is abruptly withdrawn, the body cannot adjust fast enough and withdrawal symptoms occur. Those symptoms vary depending upon the drug and the receptor system involved.

Nicotine, depending on the dosing, acts as both a stimulant by activating the sympathetic nervous system, and as a sedative, by activating the parasympathetic nervous system and reducing the activity of the sympathetic nervous system through constant stimulation (see Question 8). The body's response therefore is unique. While you may feel a general sense of activation and alertness, with a rising of the heart rate and blood pressure, and a release of adrenalin, you also feel a sense of relaxation with the stimulation of the bowels and activation of the rest and restoration response in the parasympathetic nervous system. Which system is activated more than the other is dose-dependent, and people learn how to alter the dose by changing the frequency and depth of their inhalations to vary the response. In the brain, nicotine promotes alertness and pleasure, dampens pain and appetite, and creates a general sense of relaxed attention. All of these effects are mediated not only from the direct effects of nicotine, but also from nicotine's effects on other neurotransmitter systems, including dopamine, endorphins, GABA[2], glutamate[3], and norepinephrine. Dopamine and norepinephrine improve focus and concentration, while dopamine and endorphins activate the reward system and the pleasure centers in the brain. Finally, GABA and glutamate are involved in overall brain inhibition and sedation, systems that are affected by anti-anxiety drugs such as barbiturates, benzodiazepines, and alcohol. And many of these effects persist even after a single dose of nicotine has come and gone (see Question 10). Researchers found that a single nicotine dose increases norepinephrine synthesis for at least a month.

While these effects are immediate and some long lasting, over time the brain and body adapt to the repeated exposure to the drug in order to re-establish its internal balance (homeostasis[4]). Repeated exposure of nicotine to the nicotine receptor causes the effects of it to become less sensitive. The body responds to this loss of sensitivity through a process known as up-regulation[5]. That is, the body produces more nicotinic receptors to restore the lost balance. This leads to physiological tolerance for which the smoker now increases the amount he or she smokes to re-obtain its pleasurable effects.

When you stop smoking abruptly, these physiological changes remain and withdrawal occurs. Now there are too many exposed nicotine receptors and the opposite effects of nicotine occur: Focus and concentration are lost; headaches and sensitivity to pain occur; hunger kicks in; fatigue and insomnia set in; constipation and dry mouth ensue. Finally, general dysphoria (malaise) and a craving for nicotine occur. These physiological effects can be sustained for months to one degree or another, while the body and brain readjust to the new environment by slowly rebuilding the receptor and neurotransmitter systems back to their original number and sensitivity.

Nicotine withdrawal symptoms:

Cravings to smoke

Irritability, crankiness



Inability to concentrate



Sore throat

Constipation, gas, stomach pain

Dry mouth

Sore tongue and/or gums

Postnasal drip

Tightness in the chest

  • [1] Changes that occur in the organization of the brain as a result of experience.
  • [2] The brain's major inhibitory neurotransmitter. This neurotransmitter dampens all brain activity, essentially calming the brain down at every level.
  • [3] The brain's major excitatory neurotransmitter. This neurotransmitter activates all brain activity, essentially stimulating the brain and "lifting" it up at every level.
  • [4] A property of most living systems, which are organized to maintain a stable, balanced state of equilibrium.
  • [5] The process by which a cell increases the number of receptors to a given hormone or neurotransmitter to improve its sensitivity to this molecule. (A decrease of receptors is called down-regulation.)
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