Tobacco, Nicotine, and E-Cigarettes Research Report
Is nicotine addictive?

Yes. Most smokers use tobacco regularly because they are addicted to nicotine. Addiction is characterized by compulsive drug-seeking and use, even in the face of negative health consequences. The majority of smokers would like to stop smoking, and each year about half try to quit permanently. Yet, only about 6 percent of smokers are able to quit in a given year.25 Most smokers will need to make multiple attempts before they are able to quit permanently.22 Medications including varenicline, and some antidepressants (e.g. bupropion), and nicotine-replacement therapy, can help in many cases (see "What are treatments for tobacco dependence?").26

A transient surge of endorphins in the reward circuits of the brain causes a slight, brief euphoria when nicotine is administered. This surge is much briefer than the "high" associated with other drugs. However, like other drugs of abuse, nicotine increases levels of the neurotransmitter dopamine in these reward circuits,20,21,27 which reinforces the behavior of taking the drug. Repeated exposure alters these circuits' sensitivity to dopamine and leads to changes in other brain circuits involved in learning, stress, and self-control. For many tobacco users, the long-term brain changes induced by continued nicotine exposure result in addiction, which involves withdrawal symptoms when not smoking, and difficulty adhering to the resolution to quit.28,29

The pharmacokinetic properties of nicotine, or the way it is processed by the body, contribute to its addictiveness.24 When cigarette smoke enters the lungs, nicotine is absorbed rapidly in the blood and delivered quickly to the brain, so that nicotine levels peak within 10 seconds of inhalation. But the acute effects of nicotine also dissipate quickly, along with the associated feelings of reward; this rapid cycle causes the smoker to continue dosing to maintain the drug's pleasurable effects and prevent withdrawal symptoms.30

Withdrawal occurs as a result of dependence, when the body becomes used to having the drug in the system. Being without nicotine for too long can cause a regular user to experience irritability, craving, depression, anxiety, cognitive and attention deficits, sleep disturbances, and increased appetite. These withdrawal symptoms may begin within a few hours after the last cigarette, quickly driving people back to tobacco use.

When a person quits smoking, withdrawal symptoms peak within the first few days of the last cigarette smoked and usually subside within a few weeks.31 For some people, however, symptoms may persist for months, and the severity of withdrawal symptoms appears to be influenced by a person's genes.30,31

In addition to its pleasurable effects, nicotine also temporarily boosts aspects of cognition, such as the ability to sustain attention and hold information in memory. However, long-term smoking is associated with cognitive decline and risk of Alzheimer's Disease, suggesting that short-term nicotine-related enhancement does not outweigh long-term consequences for cognitive functioning.32 In addition, people in withdrawal from nicotine experience neurocognitive deficits such as problems with attention or memory.33 These neurocognitive withdrawal symptoms are increasingly recognized as a contributor to continued smoking.34 A small research study also suggested that withdrawal may impair sleep for severely dependent smokers, and that this may additionally contribute to relapse.35

In addition to the drug's impact on multiple neurotransmitters and their receptors,30 many behavioral factors can affect the severity of withdrawal symptoms. For many people who smoke, the feel, smell, and sight of a cigarette and the ritual of obtaining, handling, lighting, and smoking the cigarette are all associated with the pleasurable effects of smoking and can make withdrawal or craving worse.36 Learning processes in the brain associate these cues with nicotine-induced dopamine surges in the reward system21—similar to what occurs with other drug addictions. Nicotine replacement therapies such as gum, patches, and inhalers, and other medications approved for the treatment of nicotine addiction may help alleviate the physiological aspects of withdrawal37–39 (see "What are treatments for tobacco dependence?"); however, cravings often persist because of the power of these cues. Behavioral therapies can help smokers identify environmental triggers of craving so they can use strategies to avoid these triggers and manage the feelings that arise when triggers cannot be.40,41

Are there other chemicals that may contribute to tobacco addiction?

Research is showing that nicotine may not be the only ingredient in tobacco that affects its addictive potential.

Smoking is linked with a marked decrease in the levels of monoamine oxidase (MAO), an important enzyme that is responsible for the breakdown of dopamine, as well as a reduction in MAO binding sites in the brain.42 This change is likely caused by some as-yet-unidentified ingredient in tobacco smoke other than nicotine, because we know that nicotine itself does not dramatically alter MAO levels. Animal research suggests that MAO inhibition makes nicotine more reinforcing, but more studies are needed to determine whether MAO inhibition affects human tobacco dependence.42

Animal research has also shown that acetaldehyde, another chemical in tobacco smoke created by the burning of sugars added as sweeteners, dramatically increases the reinforcing properties of nicotine and may also contribute to tobacco addiction.43