At a Glance

Photo: Corel

Overview

Students will examine data from animal experiments. Through this activity, a card game, and a case study, students learn that although the initial decision to take drugs of abuse is voluntary, continued use may lead to addiction, which is the continued compulsive abuse of drugs in spite of adverse consequences. Students then watch a Web site mini-documentary to learn how drugs cause long-term changes in the brain.

Major Concept

Addiction is a brain disease.

Objectives

By the end of these activities, the students will

• understand that drug abuse initially is a voluntary behavior,
• be able to define drug addiction as the continued compulsive drug abuse in the presence of adverse health or social consequences,
• understand that drug abuse and addiction are associated with long-term physical and functional changes in the brain, and
• recognize that addiction is influenced by the social and behavioral context of drug use.

Basic Science–Health Connection

Drug addiction is a complex brain disease. Preventing drug abuse and addiction and treating the disease effectively require understanding the biological, genetic, social, psychological, and environmental factors that predispose individuals to drug addiction.

Background Information

Individuals make choices to begin using drugs. Some people begin using drugs to relieve a medical condition and then continue to use the drugs after the medical need is over. Children who are depressed or who have a psychiatric disorder sometimes begin using illicit drugs to self-medicate. Other people begin taking drugs to feel pleasure, to escape the pressures of life, or to alter their view of reality. This voluntary initiation into the world of addictive drugs has strongly influenced society's view of drug abuse and drug addiction and their treatment.

When does drug abuse become drug addiction? No one becomes addicted with the first use of a drug. Drug abuse and drug addiction can be thought of as points along a continuum. Any use of a mind-altering drug or the inappropriate use of medication (either prescription or over-the-counter drugs) is drug abuse, but the point when drug abuse becomes drug addiction is less clear. Different drug abusers may reach the point of addiction at different stages. Scientists continue to investigate the factors that cause the switch between the two points.

Figure 4.1: The continuum of drug abuse and addiction.

Currently, drug addiction is defined as the continued compulsive use of drugs in spite of adverse health or social consequences.¹ Drug addicts have lost control of their drug use. Individuals who are addicted to drugs often become isolated from family or friends, have difficulty at work or school, and become involved with crime and the criminal justice system. For addicts, continuing their drug habit becomes their primary focus in life.

Certain drugs, including opiates and alcohol, cause strong physical reactions in the body when drug use stops. When a heroin addict stops taking heroin, he or she can experience a variety of symptoms ranging from watery eyes and a runny nose to irritability and loss of appetite and then diarrhea, shivering, sweating, abdominal cramps, increased sensitivity to pain, and sleep problems.² In general, withdrawal from heroin makes the abuser feel miserable. Withdrawal from other drugs, such as cocaine and amphetamines, does not lead to strong physical reactions. For most drugs, physical withdrawal symptoms can usually be controlled effectively with medications. Even though withdrawal from some drugs does not cause the abuser to have physical reactions, stopping drug use is difficult because of the changes the drugs have caused in the brain. Once the drugs stop, the abuser will have cravings, or intense desire for the drugs.³ Craving arises from the brain's need to maintain a state of homeostasis that now includes the presence of the drug. A person may experience cravings at any stage of drug abuse or addiction, even early in the experimentation phase of drug abuse. Cravings have a physical basis in the brain. Using PET imaging, scientists have shown that just seeing images of drug paraphernalia can stimulate the amygdala (part of the brain that controls memory) in drug addicts.⁴

Drugs of addiction do not merely cause short-term changes in an individual's cognitive skill and behavior. A drug "high" lasts a short time, ranging from less than an hour to 12 hours, depending on the drug and dose. The changes in the brain that result from continued drug use, however, can last a long time. Scientists believe that some of these changes disappear when drug use stops; some disappear within a short time after drug use stops, and other changes are potentially permanent. One of the first changes in the brain that occurs in response to repeated drug abuse is tolerance. Tolerance develops when a person needs increasing doses of a drug to achieve the same "high" or "rush" that previously resulted from a lower dose of the drug. Two primary mechanisms underlie the development of tolerance.³ First, the body may become more efficient at metabolizing the drug, thereby reducing the amount that enters the bloodstream. Second, the cells of the body and brain may become more resistant to the effect of the drug. For example, after continued cocaine use, neurons decrease the number of dopamine receptors, which results in decreasing cocaine's stimulatory effect. Opiates, on the other hand, do not cause a change in the number of receptors. Instead the opiate receptors become less efficient in activating the second messenger system, thus reducing the effects of the opiates.

Drugs can cause other long-term changes in the anatomy and physiology of the brain's neurons. Alcohol, methamphetamine, and MDMA (Ecstasy) can kill neurons.³ Unlike other types of cells in the body, neurons in many parts of the brain have little or no capability to regenerate. (Recent studies have shown that the adult human brain can generate new neurons in the hippocampus, a part of the brain important for learning and memory.⁵ Other parts of the brain do not show this ability.) Alcohol kills neurons in the part of the brain that helps create new memories. If those neurons die, the capability for learning decreases. Methamphetamine kills dopamine-containing neurons in animals and possibly in humans as well.⁶  MDMA kills neurons that produce another neurotransmitter called serotonin.⁷  In addition to neurotoxic effects, drugs can significantly alter the activity of the brain. PET scans of cocaine addicts show that the metabolism of glucose, the primary fuel for cells, is drastically reduced in the brain, and that this decrease in metabolism can last for many months following cessation of drug abuse.⁸

In addition to the functional and anatomical changes in the brain, drug abuse puts addicts at higher risk for other health problems. For example, inhalant abuse can lead to disruption of heart rhythms, and snorting cocaine can lead to ulcerations in the mucous membranes of the nose. In addition, drug addicts are at increased risk of contracting HIV or AIDS through shared needles. Similarly, hepatitis B and hepatitis C are much more common among drug addicts than the general population. Tuberculosis is another concern. Drug abuse and addiction also are contributing factors in motor vehicle accidents.

	Control	MDMA 2 weeks	MDMA 18 months
Cerebral Cortex         Hypothalamus	Figure 4.2: Photographs of serotonin axons in the cerebral cortex labeled with a fluorescent marker. The number of serotonin-labeled axons is dramatically reduced in the cerebral cortex at 2 weeks (B) and 18 months (C) after the last drug use. The brain of the control animal that did not receive MDMA (A) shows the dense network of labeled axons. Images E and F show changes caused by MDMA use on a different brain region, the hypothalamus. The control showing the hypothalamus in the absence of MDMA is shown in D. Photographs courtesy of G.A. Ricaurte, with the permission of the Journal of Neuroscience.

Genetic, Behavioral, and Environmental Influences on Drug Addiction

Drug addiction is not simply continuous drug abuse. Many more individuals will try an addictive drug than will become addicted. Most people know of situations in which two people use the same amount of alcohol or tobacco but have very different responses to them. Environmental, social, behavioral, and genetic factors also contribute to the development of drug addiction. Stress can increase the susceptibility to addiction.

Medical Uses of Addictive Drugs Drugs of abuse can cause long-term impairment in brain function. But, are there times when addictive drugs can be beneficial to human health? The first drug that may come to mind is morphine. During the Civil War, doctors gave morphine to wounded soldiers to relieve the pain of brutal injuries. Doctors didn't realize how addictive injected morphine was until many soldiers became addicted to the drug.2 Morphine addiction became known as "soldiers' disease." Today, morphine is a valuable medicine to relieve pain when administered with the appropriate medical supervision. Patients in hospitals receive morphine to ease their pain after surgery, and during cancer and burn treatment. Very few of these patients become addicted to morphine even though they may take it for extended periods of time.9 Another drug that has received considerable attention for its potential benefits is marijuana. Television and newspaper reports periodically present stories on the use of marijuana by terminal cancer or AIDS patients to ease their discomfort and pain. Scientists continue to investigate the potential benefits of marijuana because the studies conducted so far have been limited in focus or quality. In addition to causing changes in the brain, marijuana smoke contains many chemicals, some of which are carcinogenic to lung tissue.10 Therefore, if it is to be an effective medicine, marijuana must be available in a safer form. The active ingredient in marijuana, tetrahydrocannabinol (THC), is currently available by prescription as an oral medication. This form of the drug is likely to be neither as addictive, nor as effective, as the smoked form because the drug breaks down in the digestive tract and takes longer to get into the bloodstream. Additional studies are needed to develop a form of THC that may be inhaled. The availability of an inhalable form of THC would stimulate research into its use as a medicine. However, other obstacles also exist. Are other medications safer and more effective than THC without causing the impairment of brain function and other health problems? If so, use of THC would be difficult to justify. In March 1999, the Institute of Medicine issued a report assessing what scientific studies have shown about marijuana's potential medicinal qualities.10,11 That report concluded that smoking marijuana may lead to significant health problems and that additional studies are necessary before the medical use of marijuana can be justified. The National Institutes of Health (NIH) does support quality, controlled research studies to investigate whether marijuana, and more specifically THC, may have potential beneficial effects as a medicine. Until those studies can be completed to determine whether there is a scientific basis for medicinal claims, NIH believes marijuana should be viewed as an addictive drug that causes brain impairment, not as a medicine.

Scientists continue to investigate the factors that place one individual at greater risk of becoming addicted than another individual with a similar pattern of drug use. Individuals who have developed strong coping skills to deal with life's pressures have less risk of becoming addicted to drugs. The younger a person is when he or she begins using drugs, the more likely he or she is to become addicted. This may be true because younger individuals have not developed the coping skills necessary to deal with life's ups and downs. Furthermore, the earlier drug use begins, the less likely treatment is to be effective. In addition, genetic factors probably influence who engages in higher-risk behaviors.

The context in which a person uses an addictive drug is important. For example, some cancer patients take relatively large doses of morphine for extended periods to control pain without becoming addicted. In one study of 12,000 patients who were given opioids (primarily morphine) for acute pain, only four individuals became addicted to the drugs. In another study of 38 chronic pain patients, most of whom received opioids for four to seven years, only two patients became addicted, and both had a history of drug abuse.⁹  It is thought that addiction is rare in these pain patients because, unlike the stereotypical street addict, they are not taking the drugs to get "high" and to escape life, rather they take the drugs so they can get on with life. The drugs ease their pain and improve their quality of life.

In the 1970s, news media reported the use of marijuana and heroin by soldiers who were serving in Vietnam. Combat stress, the easy availability of drugs, and the relaxation of taboos against drug use at the time all contributed to the problem. While many soldiers did have drug problems while in Vietnam, 95 percent who were addicted to narcotics have had no addiction problems since they returned to the United States.¹³

Scientists continue to learn more about how genetic factors influence drug abuse and addiction. Heredity influences whether an individual has positive or negative sensations after smoking marijuana. One study demonstrated that identical male twins were more likely than nonidentical male twins to report similar responses to marijuana use, indicating a genetic basis for their sensations.

Animals as Research Models

Why do scientists study the brains of nonhuman animals? Scientists use animals in research studies because the use of humans is either impossible or unethical. For example, when scientists investigate the effects of drugs of abuse on brain function, either the question they are asking cannot be answered in a living human or it would be inappropriate to give drugs to them.

The use of animals as subjects in scientific research has contributed to many important advances in scientific and medical knowledge. Scientists must analyze the goals of their experiments in order to select an animal species that is appropriate. Scientists often use fruit flies (Drosophila melanogaster) when they want to learn more about genetics. However, fruit flies are not a very good model if a scientist is investigating muscle physiology; a mouse may be a better model for those experiments. Although scientists strive to develop nonanimal models for research, these models often do not duplicate the complex animal or human body. Continued progress toward a more complete understanding of human and animal health depends on the use of living animals.

Guidelines for the Use of Animals in Scientific Research Scientists who use animals as research subjects must abide by federal policies that govern the use and care of vertebrate animals in research. The Public Health Service established a policy that dictates specific requirements for animal care and use in research. This policy conforms to the Health Research Extension Act of 1985 (Public Law 99-158) and applies to all research, research training, biological testing, and other activities that involve animals.14 The principles for using and caring for vertebrate animals in research and testing are as follows: The transportation, care, and use of animals should be in accordance with the Animal Welfare Act and other applicable federal laws, guidelines, and policies. Procedures involving animals should be designed with consideration of their relevance to human or animal health, the advancement of knowledge, or the good of society. The animals selected should be of an appropriate species and quality and the minimum number required to obtain valid results. Methods such as mathematical models, computer simulation, and in vitro biological systems should be considered. Procedures should minimize discomfort, distress, and pain to the animals. Procedures that may cause more than momentary or slight pain should be performed with appropriate sedation, analgesia, or anesthesia. Animals that would suffer severe or chronic pain or distress that cannot be relieved should be painlessly killed. The living conditions of animals should be appropriate for the species. The housing, feeding, and care of animals must be directed by a veterinarian or a trained, experienced scientist. Investigators who work with animals must be appropriately qualified and trained for conducting procedures on living animals. Exceptions to any of these principles must be reviewed and approved by an appropriate committee prior to the procedure. An Institutional Animal Care and Use Committee (IACUC) oversees all animal use in each institution where animal research is conducted. The IACUC must give approval for the research plan and species to be used. IACUCs include both scientists and nonscientists from outside the institution. The nonscientists are often representatives of humane organizations.

1 | 2 | 3 | 4