Structural Biochemistry/Tobacco and Nicotine

Tobacco is a crop that is one of the main ingredients in cigarettes. It is classified as a stimulant. Tobacco leads as the drug that produces the most dependence. This dependence stems from one of its ingredients, nicotine. The most common method of consumption of this drug is through smoking. Nicotine is the main psychoactive ingredient in tobacco. Although it is most commonly used as a recreational drug, it has been shown to have medical uses. Tobacco belongs to the plant genus Nicotiana. The nicotine in these plants evolved as a mechanism to defend against insects. Insects that taste the plant would get a dose of neurotoxin. Commercially, these plants have been cultivated and farmed as a recreational drug that acts as a stimulant to the brain.

Pharmacodynamics

Acetylcholine

Nicotine has a very similar chemical structure to the neurotransmitter acetylcholine. Due to the similarity in structure, nicotine is able to bind to receptors and activate Cholinergic receptors, just as acetylcholine normally could. When acetylcholine binds to these receptors, it is thought to stimulate brain functions and help muscle control. It plays a large role in brain process speed. The structural similarity of nicotine allows it to activate these receptors much as acetylcholine can.

Absorption and metabolism of nicotine

When chewed, nicotine is absorbed readily in the lungs or through the oral mucosa. With frequent use of tobacco, levels of nicotine accumulate in the body during the day and remain overnight. Thus, tobacco users are exposed to the effects of nicotine for twenty four hours a day. Since the metabolism and the secretion of nicotine depend on a variety of factors, the drug may be detected in the body and urine even four days after the last cigarette smoked.

Behavioral Effects

Nicotine has the following behavioral effects:

Euphoria
psychostimulant
anxiousness
muscle relaxation
analgesic (reduces pain)
decrease appetite.

Nicotine also has adverse effects if used during pregnancy. It is toxic and will affect the infant. If a woman is smoking, the toxin and chemicals enter her bloodstream and subsequently the baby will get them via the blood stream. It is one of the reasons for sudden infant death syndrome. SIDS means that a baby under the age of one suddenly dies without an apparent reason. Nicotine may also cause miscarriages and low baby birth weight. Therefore, it is not advisable to smoke during pregnancy because it can have adverse effects for the fetus.

Nesbitt's Paradox

Nesbitt's paradox is one of the famous experiments and observations about nicotine. Although nicotine is classified as a stimulant, and in most ways it acts like a stimulant, nicotine also has been shown to produce relaxation. Nicotine is sometimes described as having anti-anxiety and anti-stress properties. Yet at the same time, it stimulates functions in the brain.

Stages of Tobacco Addiction

There are three stages of Tobacco addiction:

Stages	Effect
Stage 1	Psychosocial
Stage 2	Pleasurable
Stage 3	Negative Reinforcement "hooked"

Withdrawal

The onset of Tobacco withdrawal occurs around: 12–24 hours. It can last up to 10 days. The major symptoms of tobacco withdrawal include: intense cravings, irritability, anxiety, restlessness, sleep disorders, increased hunger (Mainly for carbohydrates), decreased heart rate, decreased metabolism, and fatigue. These symptoms make sense when it is realized that the nicotine in tobacco stimulates human brain function. It increases heart rate and helps combat fatigue. Withdrawal would subsequently present converse adverse effects. It makes you crave it more and kills you quicker.

Treatment Methods

Varenicline

Because tobacco is used by such a large number of people, methods of treatments also come in a wide variety. One of the ways addiction is treated for is through cognitive behavioral therapy. This is a psychotherapist method in which addicted patients have the chance to talk about their addictions. Another method people use (although less frequently) is called motivational enhancement. This is usually when therapists have sessions geared towards motivating the patient to quit. Although these therapeutic methods have been proven to work, there are also pharmacological aids that can be used to combat addiction. A few examples are listed here:

Buproprion- Its trade name is Zyban. This is a typical antidepressant. It's main action is Norepinephrine-dopamine reuptake inhibition. By blocking this, it acts as a nicotine antagonist. It doesn't allow nicotine to bind to the active site and start the normal behavioral changes associated with smoking or tobacco. Trials with placebos have shown that this drug significantly lowers cravings for nicotine and helps to stop the effects of withdrawal associated with tobacco. This drug is classified as having a low abuse potential.
Varenicline- Its trade name is Chantix. This is a nicotine partial antagonist. It is presented as a tablet that can be taken once or twice a day with water. This drug essentially blocks nicotine's ability to activate the a4b2 receptors that is responsible for the effects of nicotine. This drug can also help block nicotine withdrawal. This benefit makes it one of the more used drugs when dealing with tobacco addiction. Recent studies have shown however, that some people may exhibit hostility, agitation, suicidal thoughts, and/or depressed moods when taking this drug. However, this is only shown in people who take Varenicline while still smoking. It is important to note that this drug does not work immediately and it may take up to 12 weeks for the complete removal of addiction.

Instead of pharmacological aids, substitutes for nicotine have also been shown to help treat for addiction:

Gum- This gum helps to lower the cravings for nicotine and helps stop the adverse effects of nicotine withdrawal. This is a substitute because the gum contains small doses of nicotine. By following a preset plan, lower and lower amounts of nicotine is chewed and ideally leads to the cessation of cravings for cigarettes. However, in few cases, it has been shown that a switch to addiction for nicotine gum is possible.
Patch- The patch is a method of treatment that is similar to gum. These patches release controlled amounts of nicotine through the skin which helps stop the craving for nicotine. Ideally, it will eventually lead to a stop in the desire for cigarettes.
Non-smoke cigarettes- These are essentially cigarettes that have been 'made clean' by removing tar and other bad chemicals from the cigarette itself. However, the side effects of smoke entering the lungs and lung cancer have not been shown to be lowered by non-smoke cigarettes. Regardless, this is a method of substitution for real cigarettes.

Potential Medical Uses

Alzheimer's treatment- Alzheimer is a disease that effects the brain. It can lead to problems with memory, thinking, cognition, and behavior. Tobacco has shown signs of improving cognitive performance. One of the ingredients in tobacco 'cotinine' has been researched and shown to protect brain cells. This is highly important because if scientists are able to protect brain cells, it will slow down or even prevent brain damage caused by Alzheimer and could potentially be one of the cures.

Analgesic- Tobacco has been shown to be able to increase pain thresholds and decrease pain. It could potentially be used as an analgesic in the hospital to relieve patients of pain or increase their pain threshold before entering surgery.

Weight control- As mentioned earlier, one of the behavioral effects of tobacco is a loss of appetite. Scientists are tying to study and create a non-addictive drug that will be able to lower the cravings for food through the use of tobacco.

References

1. Hart, Carl. Drugs, Society, and Human Behavior. 13th. McGraw-Hill Humanities, 2008. Print.

2. Meeker-O'Connell, Ann. "How Nicotine Works" 2 January 2001. HowStuffWorks.com. <http://health.howstuffworks.com/wellness/drugs-alcohol/nicotine.htm> 2 December 2010.

3. Berg, Jeremy; Tymoczko, John; Stryer, Lubert. Biochemistry, 6th edition. W.H. Freeman and Company. 2007