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The Dope on Nicotine
by Rochelle Schwartz-Bloom and Gayle Gross de Núñez

Intro

If it weren't for nicotine, people wouldn't smoke tobacco. Why? Because of the more than 4,000 chemicals in tobacco smoke, nicotine is the primary one that acts on the brain, altering people's moods, appetites, and alertness in ways they find pleasant and beneficial. As the noted tobacco researcher M.A.H. Russell once wrote, "There is little doubt that if it were not for the nicotine in tobacco smoke, people would be little more inclined to smoke than they are to blow bubbles or to light sparklers."*

Unfortunately, as is widely known, nicotine has a dark side: It is highly addictive. Once smokers become hooked on it, they must get their fix of it regularly, sometimes several dozen times a day. Cigarette smoke contains 43 known carcinogens, which means that long-term smoking can amount to a death sentence. In the U.S. alone, 420,000 Americans die every year from tobacco-related illnesses.

Breaking nicotine addiction is not easy. Each year, nearly 35 million people make a concerted effort to quit smoking. Sadly, less than 7 percent succeed in abstaining for more than a year; most start smoking again within days.

So what is nicotine, and how does it insinuate itself into the smoker's brain and very being? Here, follow the trail nicotine blazes through the body, from mouth to brain.

Drug
Like cocaine derived from coca leaves and morphine drawn from opium poppies, the nicotine found in tobacco is a potent drug. Smokers, and even some scientists, say it offers certain benefits. One is enhanced performance. One study found that nonsmokers given doses of nicotine typed about 5 percent faster than they did without it. To greater or lesser degrees, users also say nicotine helps them to maintain concentration, reduce anxiety, relieve pain, and even dampen their appetites (thus helping in weight control). Unfortunately, nicotine can also produce deleterious effects beyond addiction. At high doses, as are achieved from tobacco products, it can cause high blood pressure, distress in the respiratory and gastrointestinal systems, and an increase in susceptibility to seizures and hypothermia.

Nicotine & Tobacco

Nicotine
First isolated as a chemical compound in 1828, nicotine is a clear, naturally occurring liquid that turns brown when burned and smells like tobacco when exposed to air. It is found in several species of plants, including tobacco and, perhaps surprisingly, in tomatoes, potatoes, and eggplant (though in extremely low quantities that are pharmacologically insignificant for humans). In tobacco, the highest concentration of nicotine appears in the plant's topmost leaves. A poisonous alkaloid, nicotine at high dosages has been used in everything from insecticides to darts designed to bring down elephants.

Smoker

Cigarette
As simple as it looks, the cigarette is a highly engineered nicotine-delivery device. For instance, when tobacco researchers found that much of the nicotine in a cigarette wasn't released when burned but rather remained chemically bound within the tobacco leaf, they began adding substances such as ammonia to cigarette tobacco to release more nicotine. Ammonia helps keep nicotine in its basic form, which is more readily vaporized by the intense heat of the burning cigarette than the acidic form. Most cigarettes for sale in the U.S. today contain 10 milligrams or more of nicotine. By inhaling smoke from a lighted cigarette, the average smoker takes in one to two milligrams of vaporized nicotine per cigarette.

Smoker & Nicotine

Addiction
As early as the 16^th century, it was known that tobacco use led to addiction. In 1527, the Spanish historian Bartolomé de Las Casas wrote, "I have known Spaniards on the island of Hispaniola, who were accustomed to taking [cigars] and who, being reproved and told that this was a vice, replied that they were not able to stop." Today, we know that nicotine is the cause of this dependency, and only a miniscule amount is needed to fuel addiction. Research suggests that manufacturers would have to cut nicotine levels in a typical cigarette by 95 percent to forestall its power to addict.

Heart & Lungs

Heart and Lungs
When a smoker puffs on a lighted cigarette, smoke, including vaporized nicotine, is drawn into the mouth. The skin and mucosal lining of the mouth absorb some nicotine, but the remainder flows straight down into the lungs, where it easily diffuses into the blood vessels lining the lung walls. The blood vessels carry the nicotine to the heart, which then pumps it directly to the brain. While most of the effects a smoker seeks occur in the brain, the heart takes a hit as well. Studies have shown that a smoker's first cigarette of the day can increase his or her heart rate by 10 to 20 beats a minute.

Brain activity

Brain
Scientists have found that a smoked substance reaches the brain more quickly than one swallowed, snorted (such as cocaine powder), or even injected. Indeed, a nicotine molecule inhaled in smoke will reach the brain within 10 seconds. The nicotine travels through blood vessels, which branch out into capillaries within the brain. Capillaries normally carry nutrients, but they readily accommodate nicotine molecules as well. Once inside the brain, nicotine, like most addictive drugs, triggers the release of chemicals associated with euphoria and pleasure.

Brain, capillary, nicotine

Neurons
Just as it moves rapidly from the lungs into the bloodstream, nicotine (shown here as green chevrons) also easily diffuses through capillary walls. It then migrates to the spaces surrounding neurons—gangly cells that transmit nerve impulses throughout the nervous system. These impulses are the basis of our thoughts, feelings, and moods.

Receptor

Neurotransmitters
To transmit nerve impulses to its neighbor, a neuron releases chemical messengers known as neurotransmitters (shown here as orange bars). Like nicotine molecules, the neurotransmitters drift into the so-called synaptic space between neurons, ready to latch onto the receiving neuron and thus deliver a chemical 'message' that triggers an electrical impulse.

aCH Receptor

Receptors
The neurotransmitters—in our example, acetylcholine, a common variety—bind onto receptors (shown here as green blossoms) on the surface of the recipient neuron. This opens channels in the cell surface through which enter ions, or charged atoms, of sodium (see white dots). This generates a current across the membrane of the receiving cell, which completes delivery of the 'message.'

Nicotine Binding

Binding
An accomplished mimic, nicotine competes with acetylcholine to bind to the acetylcholine receptor. It wins and, like the vanquished chemical, opens ion channels that let sodium ions into the cell. But there's a lot more nicotine around than acetylcholine, so a much larger current spreads across the membrane. This bigger current causes increased electrical impulses to travel along certain neurons. With repeated smoking, the neurons adapt to this increased electrical activity, and the smoker becomes dependent upon the nicotine.

Caudate nucleus

Caudate Nucleus
The caudate nucleus, an area of the brain that controls voluntary movement, illustrates this adaptation. Without the nicotine, neurons cannot maintain impulses at the levels they had previously. As a result, some smokers experience hand tremors between cigarettes. These "smoker's tremors" may be hard to see, because a smoker hides them by smoking another cigarette. The tremors may be a sign of withdrawal, but they will go away if the smoker gives up smoking for good.

*M.A.H. Russell, "The Smoking Habit and Its Classification, The Practitioner 212 (1974): 793.

Rochelle Schwartz-Bloom

Gayle Gross de Núñez

Dr. Rochelle D. Schwartz-Bloom is a professor of pharmacology in the Department of Pharmacology and Cancer Biology, Duke University Medical Center, and president of Savantes, a company in Durham, N.C. that produces science education materials. Dr. Gayle Gross de Núñez is director of Cajal Illustration, Chicago, Illinois. The pair coproduced the video program "Animated Neuroscience and the Action of Nicotine, Cocaine, and Marijuana in the Brain," from which this piece was adapted and expanded. For information on ordering the video, contact Films for the Humanities & Sciences of Princeton, N.J. at www.films.com.