Mind-altering drugs have intrigued human beings since the dawn of civilization. Throughout history, people have taken drugs to elevate mood, release inhibitions, distort perceptions, induce hallucinations, and modify thinking. Many of those who take mind-altering drugs restrict use to socially approved patterns. However, many others self-administer drugs to excess. Excessive drug use is our focus in this chapter and the three that follow.
Drug abuse extracts a huge toll on the individual and on society. Tobacco alone kills about 440,000 Americans each year. Alcohol and illicit drugs kill another 100,000. In addition to putting people at risk for death, drug abuse puts them at risk for long-term illness and impairs their ability to fulfill role obligations at home, school, and work. The economic burden of drug abuse is staggering: the combined direct and indirect costs from abusing nicotine, alcohol, and illicit substances are estimated at over $700 billion each year.
Drug abuse confronts clinicians in a variety of ways, making knowledge of abuse a necessity. Important areas in which expertise on drug abuse may be applied include (1) diagnosis and treatment of acute toxicity, (2) diagnosis and treatment of secondary medical complications of drug abuse, (3) facilitating drug withdrawal, and (4) providing education and counseling to maintain long-term abstinence.
Our discussion of drug abuse occurs in two stages. In this chapter, we discuss basic concepts in drug abuse. In Chapters 31, 32, and 33, we focus on the pharmacology of specific abused agents and methods of treatment.
Drug abuse can be defined as using a drug in a fashion inconsistent with medical or social norms. Traditionally, the term also implies drug use that is harmful to the individual or society. As we shall see, although we can give abuse a general definition, deciding whether a particular instance of drug use constitutes “abuse” is often difficult.
Whether or not drug use is considered abuse depends, in part, on the purpose for which a drug is taken. Not everyone who takes large doses of psychoactive agents is an abuser. For example, we do not consider it abuse to take large doses of opioids long term to relieve pain caused by cancer. However, we do consider it abusive for an otherwise healthy individual to take those same opioids in the same doses to produce euphoria.
Abuse can have different degrees of severity. Some people, for example, use heroin only occasionally, whereas others use it habitually and compulsively. Although both patterns of drug use are socially condemned and therefore constitute abuse, there is an obvious quantitative difference between taking heroin once or twice and taking it routinely and compulsively.
Note that, by the previous definition, drug abuse is culturally defined. Because abuse is culturally defined, and because societies differ from one another and are changeable, there can be wide variations in what is labeled abuse. What is defined as abuse can vary from one culture to another. For example, in the United States, moderate consumption of alcohol is not usually considered abuse. In contrast, any ingestion of alcohol may be considered abuse in some Muslim societies. Furthermore, what is defined as abuse can vary from one time to another within the same culture. For example, when a few Americans first experimented with lysergic acid diethylamide (LSD) and other psychedelic drugs, these agents were legal and their use was not generally disapproved. However, when use of psychedelics became widespread, our societal posture changed, and legislation was passed to make the manufacture, sale, and use of these drugs illegal.
As we can see, distinguishing between culturally acceptable drug use and drug use that is to be called abuse is more in the realm of social science than pharmacology. Accordingly, because this is a pharmacology text and not a sociology text, we will not attempt to define just what patterns of drug use do or do not constitute abuse. Instead, we will focus on the pharmacologic properties of abused drugs. Fortunately, we can identify the drugs that tend to be abused and discuss their pharmacology.
According to the National Institute on Drug Abuse, addiction is defined as a chronic, relapsing brain disease that is characterized by compulsive drug seeking and use, despite harmful consequences. Addiction is a very complex phenomenon that includes social, psychological, genetic, and environmental components. Please note that nowhere in this definition is addiction equated with physical dependence. As discussed later, although physical dependence can contribute to addictive behavior, it is neither necessary nor sufficient for addiction to occur.
Tolerance results from regular drug use and can be defined as a state in which a particular dose elicits a smaller response than it did with initial use. As tolerance increases, higher and higher doses are needed to elicit desired effects.
Cross-tolerance is a state in which tolerance to one drug confers tolerance to another. Cross-tolerance generally develops among drugs within a particular class, and not between drugs in different classes. For example, tolerance to one opioid (e.g., heroin) confers cross-tolerance to other opioids (e.g., morphine), but not to central nervous system (CNS) depressants, psychostimulants, psychedelics, or nicotine.
Psychological dependence can be defined as an intense subjective need for a particular psychoactive drug.
Physical dependence can be defined as a state in which an abstinence syndrome will occur if drug use is discontinued. Physical dependence is the result of neuroadaptive processes that take place in response to prolonged drug exposure.
Cross-dependence refers to the ability of one drug to support physical dependence on another drug. When cross-dependence exists between drug A and drug B, taking drug A will prevent withdrawal in a patient physically dependent on drug B, and vice versa. As with cross-tolerance, cross-dependence generally exists among drugs in the same pharmacologic family, but not between drugs in different families.
A withdrawal syndrome is a constellation of signs and symptoms that occurs in physically dependent individuals when they discontinue drug use. Quite often, the symptoms seen during withdrawal are opposite to effects the drug produced before it was withdrawn. For example, discontinuation of a CNS depressant can cause CNS excitation.
Diagnostic Criteria Regarding Drugs of Abuse
Substance use disorder is best defined as continued use of a substance despite significant substance-related problems. There exists a change in brain circuitry that persists despite detoxification. Diagnosis of substance abuse disorder is based on behaviors related to continued use of a substance.
Tolerance and withdrawal are among the criteria established by the American Psychiatric Association (APA) for having a substance use disorder. Please note, however, that tolerance and withdrawal, by themselves, are neither necessary nor sufficient for a substance use disorder to exist. Put another way, the pattern of drug use that constitutes a substance use disorder can exist in persons who are not physically dependent on drugs and who have not developed tolerance. This distinction is extremely important. Being physically dependent on a drug is not the same as being addicted. Many people are physically dependent but do not meet the criteria for a substance use disorder. These people are not considered addicts because they do not demonstrate the behavior pattern that constitutes substance dependence. Patients with terminal cancer, for example, are often physically dependent on opioids. However, because their lives are not disrupted by their medication (quite the contrary), their drug use does not meet the criteria for a substance use disorder. Similarly, some degree of physical dependence occurs in all patients who take phenobarbital to control seizure disorders. However, despite their physical dependence, patients with seizure do not carry out stereotypic addictive behavior and therefore do not have a substance use disorder.
Having stressed that physical dependence and addiction are different from each other, we must note that the two states are not entirely unrelated. As discussed later, although physical dependence is not the same as addiction, physical dependence often contributes to addictive behavior.
Factors That Contribute to Drug Abuse
Drug abuse is the end result of a progressive involvement with drugs. Taking psychoactive drugs is usually initiated out of curiosity. From this initial involvement, the user can progress to occasional use. Occasional use can then evolve into compulsive use. Factors that play a role in the progression from experimental use to compulsive use are discussed next.
Reinforcing Properties of Drugs
Reinforcement by drugs can occur in two ways. First, drugs can give the individual an experience that is pleasurable. Cocaine, for example, produces a state of euphoria. Second, drugs can reduce the intensity of unpleasant experiences. For example, drugs can reduce anxiety and stress.
The reinforcing properties of drugs can be clearly demonstrated in experiments with animals. In the laboratory, animals will self-administer most of the drugs that are abused by humans (e.g., opioids, barbiturates, alcohol, cocaine, amphetamines, phencyclidine, nicotine, caffeine). When these drugs are made freely available, animals develop patterns of drug use that are similar to those of humans. Animals will self-administer these drugs (except for nicotine and caffeine) in preference to eating, drinking, and sex. When permitted, they often die of lack of food and fluid. These observations strongly suggest that preexisting psychopathology is not necessary for drug abuse to develop. Rather, these studies suggest that drug abuse results, in large part, from the reinforcing properties of drugs themselves.
As defined earlier, physical dependence is a state in which an abstinence syndrome will occur if drug use is discontinued. The degree of physical dependence is determined largely by dosage and duration of drug use. Physical dependence is greatest in people who take large doses for a long time. The more physically dependent a person is, the more intense the withdrawal syndrome. Substantial physical dependence develops to the opioids (e.g., morphine, heroin) and CNS depressants (e.g., barbiturates, alcohol). Physical dependence tends to be less prominent with other abused drugs (e.g., psychostimulants, psychedelics, marijuana).
Physical dependence can contribute to compulsive drug use. After dependence has developed, the desire to avoid withdrawal becomes a motivator for continued dosing. Furthermore, if the drug is administered after the onset of withdrawal, its ability to alleviate the discomfort of withdrawal can reinforce its desirability. Please note, however, that although physical dependence plays a role in the abuse of drugs, physical dependence should not be viewed as the primary cause of addictive behavior. Rather, physical dependence is just one of several factors that can contribute to the development and continuation of compulsive use.
Psychological dependence is defined as an intense subjective need for a drug. Individuals who are psychologically dependent feel very strongly that their sense of well-being is dependent on continued drug use; a sense of “craving” is felt when the drug is unavailable. There is no question that psychological dependence can be a major factor in addictive behavior. For example, it is psychological dependence—and not physical dependence—that plays the principal role in causing renewed use of opioids by addicts who had previously gone through withdrawal.
Social factors can play an important role in the development of abuse. The desire for social status and approval is a common reason for initiating drug use. Also, because initial drug experiences are frequently unpleasant, the desire for social approval can be one of the most compelling reasons for repeating drug use after the initial exposure. For example, most people do not especially enjoy their first cigarette; were it not for peer pressure, many would quit before they smoked enough for it to become pleasurable. Similarly, initial use of heroin, with its associated nausea and vomiting, is often deemed unpleasant; peer pressure is a common reason for continuing heroin use long enough to develop tolerance to these undesirable effects.