Drugs, Brains, and Behavior

Preface

How Science Has Revolutionized the Understanding of Drug Addiction
Throughout much of the last century, scientists studying drug abuse labored in the shadows of powerful myths and misconceptions about the nature of addiction. When science began to study addictive behavior in the 1930s, people addicted to drugs were thought to be morally flawed and lacking in willpower. Those views shaped society's responses to drug abuse, treating it as a moral failing rather than a health problem, which led to an emphasis on punitive rather than preventative and therapeutic actions. Today, thanks to science, our views and our responses to drug abuse have changed dramatically. Groundbreaking discoveries about the brain have revolutionized our understanding of drug addiction, enabling us to respond effectively to the problem.

As a result of scientific research, we know that addiction is a disease that affects both brain and behavior. We have identified many of the biological and environmental factors and are beginning to search for the genetic variations that contribute to the development and progression of the disease. Scientists use this knowledge to develop effective prevention and treatment approaches that reduce the toll drug abuse takes on individuals, families, and communities.

"Drug addiction is a brain disease that can be treated." Nora D. Volkow, M.D. Director National Institute on Drug Abuse

Despite these advances, many people today do not understand why individuals become addicted to drugs or how drugs change the brain to foster compulsive drug abuse. This booklet aims to fill that knowledge gap by providing scientific information about the disease of drug addiction, including the many harmful consequences of drug abuse and the basic approaches that have been developed to prevent and treat the disease. At the National Institute on Drug Abuse (NIDA), we believe that increased understanding of the basics of addiction will empower people to make informed choices in their own lives, adopt science-based policies and programs that reduce drug abuse and addiction in their communities, and support scientific research that improves the Nation's well-being.

Nora D. Volkow, M.D.
Director
National Institute on Drug Abuse

Tobacco/Nicotine

Brief Description: One of the most heavily used addictive drugs in the U.S. Effects: Nicotine is highly addictive. The tar in cigarettes increases a smoker's risk of lung cancer, emphysema, and bronchial disorders. The carbon monoxide in smoke increases the chance of cardiovascular diseases. Secondhand smoke causes lung cancer in adults and greatly increases the risk of respiratory illnesses in children. Statistics and Trends: In 2006, nearly 73 million Americans age 12 and older had used a tobacco product at least once in the month prior to being surveyed. Source: National Survey on Drug Use and Health; http://www.samhsa.gov/. The NIDA-funded 2007 Monitoring the Future Study showed that 7.1% of 8th graders, 14.0% of 10th graders, and 21.6% of 12th graders had used cigarettes and 3.2% of 8th graders, 6.1% of 10th graders, and 6.6% of 12th graders had used smokeless tobacco at least once in the month prior to being surveyed. Source: Monitoring the Future http://www.monitoringthefuture.org/. NID

NIDA InfoFacts

Through the use of cigarettes, cigars, and chewing tobacco, nicotine is one of the most heavily used addictive drugs in the United States. In 2004, 29.2 percent of the U.S. population 12 and older—70.3 million people—used tobacco at least once in the month prior to being interviewed.* This figure includes 3.6 million young people age 12 to 17. Young adults aged 18 to 25 reported the highest rate of current use of any tobacco products (44.6 percent) in 2004.

Findings for high school youth indicate that 25.9 percent of 8th-graders, 38.9 percent of 10th-graders, and 50.0 percent of 12th-graders had ever smoked cigarettes when asked in 2005.** These figures were lower for all three grades from 2004 data, and for 8th-graders and 12th-graders, the decreases were statistically significant.

Statistics from the Centers for Disease Control and Prevention indicate that tobacco use remains the leading preventable cause of death in the United States, causing approximately 440,000 premature deaths each year and resulting in an annual cost of more than $75 billion in direct medical costs attributable to smoking. (See www.cdc.gov/tobacco/issue.htm.) Over the past four decades, cigarette smoking has caused an estimated 12 million deaths, including 4.1 million deaths from cancer, 5.5 million deaths from cardiovascular diseases, 2.1 million deaths from respiratory diseases, and 94,000 infant deaths related to mothers smoking during pregnancy. (See www.cdc.gov/nccdphp/publications/aag/osh.htm.)

Secondhand smoke, also known as environmental tobacco smoke, is a mixture of the smoke given off by the burning end of tobacco products (sidestream smoke) and the mainstream smoke exhaled by smokers. It is a complex mixture containing many chemicals (including formaldehyde, cyanide, carbon monoxide, ammonia, and nicotine), many of which are known carcinogens. Nonsmokers exposed to secondhand smoke at home or work increase their risk of developing heart disease by 25 to 30 percent and lung cancer by 20 to 30 percent. In addition, secondhand smoke causes respiratory problems in nonsmokers such as coughing, phlegm, and reduced lung function. Children exposed to secondhand smoke are at an increased risk for sudden infant death syndrome, acute respiratory infections, ear problems, and more severe asthma.

Health Hazards

Since 1964, 28 Surgeon General's reports on smoking and health have concluded that tobacco use is the single most avoidable cause of disease, disability, and death in the United States. In 1988, the Surgeon General concluded that cigarettes and other forms of tobacco, such as cigars, pipe tobacco, and chewing tobacco, are addictive and that nicotine is the drug in tobacco that causes addiction. Nicotine provides an almost immediate "kick" because it causes a discharge of epinephrine from the adrenal cortex. This stimulates the central nervous system and endocrine glands, which causes a sudden release of glucose. Stimulation is then followed by depression and fatigue, leading the user to seek more nicotine.

Nicotine is absorbed readily from tobacco smoke in the lungs, and it does not matter whether the tobacco smoke is from cigarettes, cigars, or pipes. Nicotine also is absorbed readily when tobacco is chewed. With regular use of tobacco, levels of nicotine accumulate in the body during the day and persist overnight. Thus, daily smokers or chewers are exposed to the effects of nicotine for 24 hours each day. Adolescents who chew tobacco are more likely than nonusers to eventually become cigarette smokers.

Addiction to nicotine results in withdrawal symptoms when a person tries to stop smoking. For example, a study found that when chronic smokers were deprived of cigarettes for 24 hours, they had increased anger, hostility, and aggression, and loss of social cooperation. Persons suffering from withdrawal also take longer to regain emotional equilibrium following stress. During periods of abstinence and/or craving, smokers have shown impairment across a wide range of psychomotor and cognitive functions, such as language comprehension.

Women who smoke generally have earlier menopause. Pregnant women who smoke cigarettes run an increased risk of having stillborn or premature infants or infants with low birth weight. Children of women who smoked while pregnant have an increased risk for developing conduct disorders. National studies of mothers and daughters have also found that maternal smoking during pregnancy increased the probability that female children would smoke and would persist in smoking.

In addition to nicotine, cigarette smoke is primarily composed of a dozen gases (mainly carbon monoxide) and tar. The tar in a cigarette, which varies from about 15 mg for a regular cigarette to 7 mg in a low-tar cigarette, exposes the user to an increased risk of lung cancer, emphysema, and bronchial disorders.

The carbon monoxide in tobacco smoke increases the chance of cardiovascular diseases. The Environmental Protection Agency has concluded that secondhand smoke causes lung cancer in adults and greatly increases the risk of respiratory illnesses in children and sudden infant death.

Promising Research

Research has shown that nicotine, like cocaine, heroin, and marijuana, increases the level of the neurotransmitter dopamine, which affects the brain pathways that control reward and pleasure. Scientists have pinpointed a particular molecule [the beta 2 (b2)] subunit of the nicotine cholinergic receptor as a critical component in nicotine addiction. Mice that lack this subunit fail to self-administer nicotine, implying that without the b2 subunit, the mice do not experience the positive reinforcing properties of nicotine. This finding identifies a potential site for targeting the development of nicotine addiction medications.

Other research found that individuals have greater resistance to nicotine addiction if they have a genetic variant that decreases the function of the enzyme CYP2A6. The decrease in CYP2A6 slows the breakdown of nicotine and protects individuals against nicotine addiction. Understanding the role of this enzyme in nicotine addiction gives a new target for developing more effective medications to help people stop smoking. Medications might be developed that can inhibit the function of CYP2A6, thus providing a new approach to preventing and treating nicotine addiction.

Another study found dramatic changes in the brain's pleasure circuits during withdrawal from chronic tobacco use. These changes are comparable in magnitude and duration to similar changes observed during withdrawal from other abused drugs such as cocaine, opiates, amphetamines, and alcohol. Scientists found significant decreases in the sensitivity of the brains of laboratory rats to pleasurable stimulation after nicotine administration was abruptly stopped. These changes lasted several days and may correspond to the anxiety and depression experienced by humans for several days after quitting smoking "cold turkey." The results of this research may help in the development of better treatments for the withdrawal symptoms that may interfere with individuals' attempts to quit.

Treatment

Some individuals simply are able to stop smoking. For others, studies have shown that pharmacological treatment combined with behavioral treatment, including psychological support and skills training to overcome high-risk situations, results in some of the highest long-term abstinence rates. Generally, rates of relapse for smoking cessation are highest in the first few weeks and months and diminish considerably after about 3 months.

Behavioral economic studies find that alternative rewards and reinforcers can reduce cigarette use. One study found that the greatest reductions in cigarette use were achieved when smoking cost was increased in combination with the presence of alternative recreational activities.

Nicotine chewing gum is one medication approved by the Food and Drug Administration (FDA) for the treatment of nicotine dependence. Nicotine in this form acts as a nicotine replacement to help smokers quit smoking. The success rates for smoking cessation treatment with nicotine chewing gum vary considerably across studies, but evidence suggests that it is a safe means of facilitating smoking cessation if chewed according to instructions and restricted to patients who are under medical supervision.

Another approach to smoking cessation is the nicotine transdermal patch, a skin patch that delivers a relatively constant amount of nicotine to the person wearing it. A research team at NIDA's Intramural Research Program studied the safety, mechanism of action, and abuse liability of the patch that was consequently approved by FDA. Both nicotine gum and the nicotine patch, as well as other nicotine replacements such as sprays and inhalers, are used to help people fully quit smoking by reducing withdrawal symptoms and preventing relapse while undergoing behavioral treatment.

Another tool in treating tobacco addiction is a medication that goes by the trade name Zyban. This is not a nicotine replacement, as are the gum and patch. Rather, this works on other areas of the brain, and its effectiveness is in helping to make nicotine craving, or thoughts about cigarette use, more controllable in people who are trying to quit.

Extent of Use

Monitoring the Future Survey (MTF)

Despite the demonstrated health risks associated with cigarette smoking, young Americans continue to smoke. However, 30-day*** smoking rates among high school students have declined from peaks reached in 1996 for 8th-graders (21.0 percent) and 10th-graders (30.4 percent) and in 1976 for 12th-graders (38.8 percent). In 2005, 30-day rates had dropped to 9.3 percent for 8th-graders, 14.9 percent for 10th-graders, and 23.2 percent for 12th-graders.

The decrease in smoking rates among young Americans corresponds to several years in which increased proportions of teens said they believe there is a "great" health risk associated with cigarette smoking and expressed disapproval of smoking one or more packs of cigarettes a day. Students' personal disapproval of smoking has risen for some years. In 2005, for example, the percentage of 12th-graders disapproving of smoking one or more packs of cigarettes per day increased significantly, from 76.2 percent in 2004 to 79.8 percent in 2005.