Students examine data from animal experiments, play a card game, and examine a case study. They 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 despite adverse consequences. Students then watch a minidocumentary online to learn how drugs cause long-term changes in the brain.
Addiction is a brain disease.
By the end of these activities, the students will
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.
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 or teens who are depressed or who have another psychiatric disorder sometimes begin using illicit drugs in an attempt 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? It rarely happens 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 people may reach the point of addiction at different stages. Scientists continue to investigate the factors that contribute to the transition to drug addiction.
Drug addiction is defined as the continued compulsive use of drugs despite adverse health or social consequences.1 Drug-addicted people 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, may commit crimes, and become involved with the criminal justice system. For a person addicted to drugs, continuing to take them becomes the primary focus in life.
Certain drugs, including opioids and alcohol, cause strong physical reactions in the body when drug use stops. When a person addicted to heroin 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 people feel miserable. Withdrawal from alcohol can cause serious effects such as seizures and even death. Withdrawal from other drugs, such as cocaine and amphetamines, does not lead to strong physical reactions, but it may make the person feel depressed or lethargic. For most drugs, physical withdrawal symptoms can usually be controlled effectively with medications. Even though withdrawal from some drugs does not cause the person abusing them 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 person 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 relies on 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 involved in emotional memory) in an addicted person.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, dose, and route of administration. 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 may occur 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 brain. 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. Opioids, on the other hand, do not cause a change in the number of receptors. Instead the opioid receptors become less efficient in activating associated cellular processes, thus reducing the effects of the opioids.
Drugs can cause other long-term changes in the anatomy and physiology of the brain’s neurons. Alcohol, methamphetamine, and MDMA (ecstasy) have been shown to be neurotoxic in animal studies.3 Unlike other types of cells in the body, neurons in many parts of the brain have little or no capacity 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 have not been shown to have this ability.) Alcohol kills neurons in a part of the brain that helps create new memories (the hippocampus and mammillary bodies). If those neurons die, the capacity for learning decreases. Methamphetamine is toxic to dopamine-containing neurons in animals and possibly in humans as well.6 MDMA has been shown in animal studies to damage the axon terminals of 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 people addicted to cocaine show that the metabolism of glucose, the primary fuel for cells, is drastically reduced in the brain; this decrease in metabolism can last for many months after drug abuse stops.8
In addition to the functional and anatomical changes in the brain, drug abuse puts people 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, injection drug users (IDUs) are at higher risk of contracting HIV through the sharing of potentially contaminated 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.
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.9 Stress can increase the susceptibility to addiction.
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. Additionally, the frontal cortex of the adolescent brain isn’t fully mature until age 24.10 This area of the brain is responsible for judgment and for inhibiting impulsivity and risk-taking behavior. In addition, genetic factors probably influence who engages in higherrisk behaviors.
The context in which a person uses an addictive drug greatly contributes to its behavioral effects and the risk of abuse and addiction. For example, some cancer patients take relatively large doses of morphine for extended periods to control pain without becoming addicted. It has been proposed that addiction is rare in these patients because, in contrast to addicted individuals, these patients are motivated not by a compulsive urge to seek a high but by a physiologic need to ease their pain and improve their quality of life.
Medical Uses of Addictive Drugs
It is well known that otherwise safe medications can turn harmful if abused or taken without prescription or supervision. The other side of this coin is that many drugs of abuse are themselves, or have been found to contain, active ingredients that can be therapeutic. A good example is morphine. During the Civil War, doctors gave morphine to wounded soldiers to relieve the pain of 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.
Another drug that has received considerable attention for its potential medical 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. Following up on such anecdotal evidence, several scientific studies have been able to corroborate at least some of the claims about marijuana’s beneficial effects on appetite, nausea, and certain types of pain. However, marijuana’s addictive properties and its usual delivery by smoke inhalation—which exposes the lungs to many toxic chemicals—make it an unappealing candidate for medications development. Rather, it is likely that our understanding of the biology of marijuana’s active ingredients, such as tetrahydrocannabinol (THC), will lead to improved medications for a variety of conditions, ranging from obesity and addiction to neuropathic pain in multiple sclerosis (MS) patients, chronic pain in advanced cancer patients, nausea, and wasting syndrome.11
The risk of becoming addicted to prescription pain medications is minimal in patients who are treated on a short-term basis; however, the risk for those with chronic pain is less well understood. Some studies have shown that those most vulnerable to becoming addicted to prescription pain medications have a history of psychological disorders, prior substance abuse problems, or a family history of these disorders. Pain management for patients who have substance abuse disorders is particularly challenging for the medical profession. However, these patients can still be successfully treated with opioid pain medications, although they may need to be admitted to a treatment or recovery program and monitored closely if controlled substances are prescribed for pain.
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. Although many soldiers did have drug problems while in Vietnam, 95 percent were not addicted to drugs after they returned to the United States.12 This illustrates the profound effect that environmental circumstances can have on drug taking and drug addiction.
In addition, scientists are working to identify genetic factors that contribute to drug abuse and addiction. Studies of identical twins indicate that as much as half of an individual’s risk of becoming addicted to nicotine, alcohol, or other drugs depends on his or her genes. Recent technical advances in DNA analysis have enabled researchers to untangle complex genetic interactions by examining a person’s entire genome at once. A series of studies has identified a certain variant in the gene for a nicotinic receptor subunit that more than doubles the risk for addiction among smokers, as well as increasing their vulnerability to lung cancer and peripheral arterial disease.
Why do scientists study the brains of laboratory 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 a person the drugs.
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 or behavior; 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.13 The principles for using and caring for vertebrate animals in research and testing are as follows:
|For the class||For each student|
|1 transparency of Master 4.4, Playing the Game
1 transparency of Master 4.5, Who Is Addicted?
|1 copy of Master 4.1, Data for Rat Self-administration Experiment
1 copy of Master 4.2, Worksheet for Rat Experiment Data
1 copy of Master 4.3, Evaluating the Experiment
1 copy of Master 4.6, Long-Term Effects of Drugs on the Brain (only if not using the Web-based version)
|2||colored pencils, overhead projector, transparency|
|3||playing cards (one deck for each group of 3 students; see Preparation section), overhead projector|
Gather decks of playing cards for use in Activity 3. Each group of three students can share one deck of cards. Separate the face cards (jacks, queens, and kings) and place them in one pile. Place the aces and number cards in another pile.
Arrange for students to have access to computers for viewing the minidocumentary online in Activity 5.
Students will respond with a variety of answers. Some will give examples of illegal drugs, such as marijuana or cocaine, others may give the names of prescription medications. If so, prompt students to think about a definition for the word drug. Some students will describe a drug either as an illegal substance that harms a person’s health or as a chemical that a person takes to treat a disease or illness. At this point, based on students’ knowledge, both definitions are correct.
Several terms will be introduced in this lesson. It is very important to use these terms according to the definitions provided.
According to these definitions, all medications are drugs, but not all drugs are medications. This module uses the word “drug” to refer to psychoactive drugs, or drugs of abuse. Drug abuse refers to the use of illicit drugs or to the inappropriate use of a legal drug or substance, such as alcohol, nicotine, prescription drugs, or inhalants.
Societal and political factors sometimes influence into which category a substance falls. Alcohol and nicotine (tobacco) are drugs that are illegal to use and possess if the individual is below legal age, but not for adults to possess and use responsibly. Also, inhalants (paints, glues, and sprays, for example) are not illegal to possess when they are used for their intended purposes. However, they are drugs when used improperly to alter brain function.
Some students will raise the idea that medications can also be drugs if they are used inappropriately. For example, overuse of a prescription medication, such as a sedative, is inappropriate and wouldn’t be considered a medication in that case. Alternatively, students may indicate that morphine is an illegal drug when used without medical supervision, but is a valuable medicine when used appropriately in a hospital, or at home, to relieve pain associated with various diseases. Students may also propose that marijuana can be a medication to relieve the pain that accompanies various diseases. (In some states, marijuana is legal as a medication, but is illegal according to federal law.) If students bring this up, point out to them that scientists need to continue studying marijuana or its active ingredients to determine if it may be effective as a medicine. Marijuana contains hundreds of chemical compounds; the effects of most of these compounds in the body are unknown. Marijuana also poses many problems outside of the brain—for the lungs, for example, because it is usually smoked. Use this as an opportunity to inform students that scientific research is being done to determine whether marijuana or other cannabinoidbased medications are more effective than other medicines (see the Background Information section).
Students may provide a wide range of answers to this question including peer pressure, experimentation, boredom, or fun. Some students may also respond that people take drugs to escape from life’s pressures.
Students may ask what substance was injected in response to the press of the stimulus lever. Tell students that the answer to that question will be revealed during the activity.
The graph of the data for each rat will have two lines, one for the stimulus lever and one for the food lever. Students can use a different color of pencil for plotting each set of data, or they can use a solid line and a dashed line to distinguish between the two graph lines.
Sample Answers to Questions on Master 4.3
Question 1. Why do the rats press a lever the first time?
The rats initially press a lever while they are exploring the cage. A rat may even press the lever by accident. Whether a rat presses the food lever or the stimulus lever first is usually random.
Question 2. Compare the lever-pressing behaviors of the four different rats. Which rat pressed the stimulus lever the most? Which one pressed the stimulus lever the least? Which rat pressed the food lever the most? Which one pressed the food lever the least?
Rats A and C pressed the stimulus lever about the same number of times and many more times than either Rat B or Rat D. Rats B and D did not press the stimulus lever very many times, but they pressed the food lever more times than Rats A and C did. Overall, Rats A and C behaved similarly and Rats B and D behaved similarly.
Question 3. Rat A was injected with cocaine each time it pressed the stimulus lever. Can you use this fact to explain why Rat A behaved the way it did?
The cocaine activated the reward system in the brain and caused the rat to continue its stimulus-lever-pressing behavior. If necessary, remind students that the reward system is the part of the brain stimulated by drugs to cause feelings of pleasure.
Question 4. Based on the data you analyzed, do you think Rat B was injected with cocaine when it pressed the stimulus lever? From what you have learned so far in this unit, do you think Rat B was injected with a different addictive drug when it pressed the stimulus lever? Why?
It appears that Rat B was not injected with cocaine when it pressed the stimulus lever because its behavior was very different from Rat A. If Rat B was injected with cocaine or another addictive drug, it should display behavior similar to Rat A.
(Rat B actually received a saline injection when it pressed the stimulus lever.)
Question 5. Do you think Rat C received cocaine when it pressed the stimulus lever? Why?
It is possible that Rat C received cocaine when it pressed the stimulus lever because its behavior was very similar to that of Rat A. However, you cannot be sure that it was cocaine.
Question 6. Rat C did not receive an injection of cocaine when it pressed the stimulus lever. When Rat C pressed the stimulus lever, it received a mild electrical stimulation in the brain. On the basis of what you have learned, can you predict what part of the brain was stimulated?
The reward system (ventral tegmental area or nucleus accumbens) is the part of the brain stimulated. Stimulation in that area of the brain caused the rat to continue pressing the stimulus lever.
Question 7. Rat D also received a mild electrical stimulation in the brain when it pressed the stimulus lever. Do you think the same part of the brain was stimulated in Rat D as was stimulated in Rat C? Why?
Rat D did not receive an electrical stimulation in the same part of the brain that was stimulated in Rat C. If the same part of the brain, the reward system, was stimulated, Rat D should behave similarly to Rat C.
(Rat D received an electrical shock in the cerebellum, which is not part of the reward pathway.)
Question 8. Why did Rats A and C press the stimulus lever more than the food lever?
Rats A and C received a greater “reward” when they pressed the stimulus lever than they did when they pressed the food lever.
Question 9. Why did Rats B and D press the food lever more than the stimulus lever?
Rats B and D received greater “reward” when they pressed the food lever than they did when they pressed the stimulus lever.
Question 10. Why did the scientists who conducted this experiment include Rats B, C, and D? How did the data from those rats help scientists understand more about how cocaine acts in the brain?
Rats B, C, and D were used as controls in this experiment. Rat B received a saline injection after pressing the stimulus lever. (The cocaine that Rat A received was dissolved in a saline solution.) Because Rat B’s behavior differed from Rat A’s behavior, this suggests that the cocaine that Rat A received caused the frequent stimuluslever- pressing behavior. Because both rats had a canula inserted to deliver the solution, the process of inserting the canula is not sufficient to cause Rat A’s behavior.
The data from Rat C reveal that electrical stimulation of the VTA elicits behavior similar to that caused by cocaine injection. Because cocaine is known to act on neurons in the VTA, these data reinforce the findings from Rat A that the cocaine acting on the VTA neurons causes the frequent stimulus- lever-pressing behavior.
Rat D received electrical stimulation in the cerebellum after pressing the stimulus lever. The cerebellum is not part of the reward system. These data show that stimulation to a discrete brain area, the reward system, causes Rat C’s behavior. Inserting the electrode into other areas of the brain is not sufficient to elicit the rapid stimulus-lever-pressing behavior observed in Rat C.
Question 11. Do you think that Rats A and C will stop pressing the stimulus lever if they continue to receive the same stimulation each time they press it? Why?
On basis of the data, it does not seem likely that Rats A and C would stop pressing the stimulus lever because the number of times it is pressed continues to increase within each five-minute period. Students may notice that Rat A pressed the stimulus lever more times during the last five-minute period of the experiment than it did during the first five-minute period.
Question 12. On the basis of what you learned from these data, what might this investigation tell you about drug use by humans? Explain your view.
The data from the rat experiment show that the use of addictive drugs is reinforcing. Rats who are given cocaine want more cocaine. Because rats are mammals just as humans are and many of their organs function in ways similar to those in humans, the data suggest that drug use in humans is likely to be reinforcing as well: humans who take drugs will probably want to continue taking drugs.
People who are addicted to drugs continue to take drugs despite negative consequences. They know that their family, social, or career interactions are disrupted by their drug abuse, but they cannot stop. Drug-taking becomes compulsive. Rats A and C became conditioned to the activation of the reward system by the administration of cocaine or electrical stimulation in the VTA in response to a lever press. Those rats continued to press the stimulus bar in their cages and ignored the food lever. The cocaine or electrical stimulation in the VTA was a bigger reward for the rats than was the food. In humans, drugs cause a compulsive need for more drugs.
Although it is not appropriate to refer to the rats as addicted to cocaine, those rats would have experienced adverse effects if the experiment continued for a long time. If the experiment continued and the rats continued to push only the stimulus lever, the lack of food and water would lead to adverse health consequences. If the scientists did not stop the experiment, the rats would have continued to press the stimulus lever until they died from a cocaine overdose.
Humans addicted to drugs are most concerned with their next drug use. Because of this, they often eat little or poorly and consequently suffer the adverse health consequences of poor nutrition.
Students should be able to use the previously given definition of addiction and the results of the cocaine self-administration experiments with rats to differentiate between drug abuse and addiction. Abuse is voluntary; addiction is the continued compulsive drug use despite adverse health or social consequences.
Scientists do not know what causes a person who is abusing drugs to become addicted. Continuing research is attempting to answer this question.
Next: Lesson 4 (Page 2 of 2)