html xmlns=”http://www.w3.org/1999/xhtml” xml:lang=”en” style=”font-size:1.250rem;”>
Drug Abuse I
Basic Considerations
Laura D. Rosenthal DNP, ACNP, FAANP
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.
Definitions
Drug Abuse
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.
Addiction
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.
Other Definitions
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.
Physical Dependence
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
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
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.
Drug Availability
Drug availability is clearly a factor in the development and maintenance of abuse. Abuse can flourish only in environments where drugs can be readily obtained. In contrast, where procurement is difficult, abuse is minimal. The ready availability of drugs in hospitals and clinics is a major reason for the unusually high rate of addiction among pharmacists, nurses, and physicians.
Vulnerability of the Individual
Some individuals are more prone to becoming drug abusers than others. By way of illustration, let’s consider three individuals from the same social setting who have equal access to the same psychoactive drug. The first person experiments with the drug briefly and never uses it again. The second person progresses from experimentation to occasional use. The third goes on to take the drug compulsively. Because social factors, drug availability, and the properties of the drug itself are the same for all three people, these factors cannot explain the three different patterns of drug use. We must conclude, therefore, that the differences must lie in the people: one individual was not prone to drug abuse, one had only moderate tendencies toward abuse, and the third was highly vulnerable to becoming an abuser.
Several psychological factors have been associated with tendencies toward drug abuse. Drug abusers are frequently individuals who are impulsive, have a low tolerance for frustration, and are rebellious against social norms. Other psychological factors that seem to predispose individuals to abusing drugs include depressive disorders, anxiety disorders, and antisocial personality. It is also clear that individuals who abuse one type of drug are likely to abuse other drugs.
There is speculation that some instances of drug abuse may actually represent self-medication to relieve emotional discomfort. For example, some people may use alcohol and other depressants to control severe anxiety. Although their drug use may appear excessive, it may be no more than they need to neutralize intolerable feelings.
Genetics also contribute to drug abuse. Vulnerability to alcoholism, for example, may result from an inherited predisposition.
Neurobiology of Addiction
Repeated use of an addictive drug contributes to the transition from voluntary drug use to compulsive use by causing molecular changes in the brain. Each time the drug is taken, it causes changes that promote further drug use. With repeated drug exposure, these changes are reinforced, making drug use increasingly more difficult to control.
Molecular changes occur in the reward circuit—a system that normally serves to reinforce behaviors essential for survival, such as eating and reproductive activities. Neurons of the reward circuit originate in the ventral tegmental area of the midbrain and project to the nucleus accumbens. Their major transmitter is dopamine. Under normal circumstances, biologically critical behavior, such as sexual intercourse, activates the circuit. The resultant release of dopamine rewards and reinforces the behavior. Like natural positive stimuli, addictive drugs can also activate the circuit and thereby cause dopamine release. In fact, drugs are so effective at activating the circuit that the amount of dopamine released may be 2 to 10 times the amount released by natural stimuli. Ultimately, whether the system is activated by use of drugs or by behavior essential for survival, the outcome is the same: a tendency to repeat the behavior that turned the system on. With repeated activation over time, the system undergoes synaptic remodeling, thereby consolidating changes in brain function. This neural remodeling persists after drug use has ceased.
An important aspect of drug-induced remodeling is a phenomenon known as downregulation, which serves to reduce the response to drugs. Because drugs release abnormally large amounts of dopamine, the reward circuit is put in a state of excessive activation. In response, the brain (1) produces less dopamine and (2) reduces the number of dopamine receptors. As a result, responses to drugs are reduced. Unfortunately, the ability of natural stimuli to activate the circuit is reduced as well. In the absence of pleasurable feelings from natural stimuli, the abuser is left feeling flat, lifeless, and depressed. The good news is that, when drug use stops, neural remodeling tends to gradually reverse.
Principles of Addiction Treatment
Drug addiction is a treatable disease of the brain. With therapy, between 40% and 60% of addicts can reduce drug use. The first science-based guide on addiction therapy—Principles of Drug Addiction Treatment—was published by the National Institute on Drug Abuse in 1999, and later revised in 2009 and 2012. The guide centers on 13 principles of effective treatment, shown in Box 30.1.
Ideally, the goal of treatment is complete cessation of drug use. However, total abstinence is not the only outcome that can be considered successful. Treatment that changes drug use from compulsive to moderate will permit increased productivity, better health, and a decrease in socially unacceptable behavior. Clearly, this outcome is beneficial both to the individual and to society—even though some degree of drug use continues. It must be noted, however, that in the treatment of some forms of abuse, nothing short of total abstinence can be considered a true success. Experience has shown that abusers of cigarettes, alcohol, and opioids are rarely capable of sustained moderation. Hence, for many of these individuals, abstinence must be complete if there is to be any hope of avoiding a return to compulsive use.
Recovery from addiction is a prolonged process that typically requires multiple treatment episodes because addiction is a chronic, relapsing illness. As such, periods of treatment-induced abstinence will very likely be followed by relapse. This does not mean that treatment has failed. Rather, it simply means that at least one more treatment episode is needed. Eventually, many patients achieve stable, long-term abstinence, along with a more productive and rewarding life.
Because addiction is a complex illness that affects all aspects of life, the treatment program must be comprehensive and multifaceted. In addition to addressing drug use itself, the program should address any related medical, psychological, social, vocational, and legal problems. Obviously, treatment must be tailored to the individual; no single approach works for all people. Multiple techniques are employed. Techniques with proven success include (1) group and individual therapy directed at resolving emotional problems that underlie drug use, (2) substituting alternative rewards for the rewards of drug use, and (3) use of pharmacologic agents to modify the effects of abused drugs. The most effective treatment programs incorporate two or more of these methods. When possible, a specialist in addiction medicine or substance use should be involved in the patient’s care.
The Controlled Substances Act
The Comprehensive Drug Abuse Prevention and Control Act of 1970, known informally as the Controlled Substances Act (CSA), is the principal federal legislation addressing drug abuse. One objective of the CSA is to reduce the chances that drugs originating from legitimate sources will be diverted to abusers. To accomplish this goal, the CSA sets forth regulations for the handling of controlled substances by manufacturers, distributors, pharmacists, nurses, and physicians. Enforcement of the CSA is the responsibility of the Drug Enforcement Agency (DEA), an arm of the U.S. Department of Justice.
Record Keeping
To keep track of controlled substances that originate from legitimate sources, a written record must be made of all transactions involving these agents. Every time a controlled substance is purchased or dispensed, the transfer must be recorded. Physicians, pharmacists, and hospitals must keep an inventory of all controlled substances in stock. This inventory must be reported to the DEA every 2 years. Although not specifically obliged to do so by the CSA, many hospitals use medication dispensing machines that count the controlled substances dispensed during each shift.
Drug Enforcement Agency Schedules
Each drug preparation regulated under the CSA has been assigned to one of five categories: Schedule I, II, III, IV, or V. Drugs in Schedule I have a high potential for abuse and no approved medical use in the United States. In contrast, drugs in Schedules II through V all have approved applications. Assignment to Schedules II through V is based on abuse potential and potential for causing physical or psychological dependence. Of the drugs that have medical applications, those in Schedule II have the highest potential for abuse and dependence. Drugs in the remaining schedules have decreasing abuse and dependence liabilities. Table 30.1 lists the primary drugs that come under the five DEA Schedules.
TABLE 30.1
Drug Enforcement Agency Classification of Controlled Substances
| Schedule I Drugs | Schedule II Drugs | Schedule III Drugs | Schedule IV Drugs | Schedule V Drugs |
|
|
|
|
Scheduling of drugs under the CSA undergoes periodic reevaluation. With increased understanding of the abuse and dependence liabilities of a drug, the DEA may choose to reassign it to a different Schedule. For example, hydrocodone (the opiate in Vicodin) was recently switched from Schedule III to Schedule II.
Prescriptions
The CSA places restrictions on prescribing drugs in Schedules II through V. (Drugs in Schedule I have no approved uses and hence are not prescribed.) Only prescribers registered with the DEA are authorized to prescribe controlled drugs. Regulations on prescribing controlled substances are summarized next.
Schedule II
All prescriptions for Schedule II drugs must be typed or filled out in ink or indelible pencil and signed by the prescriber. Alternatively, prescribers may submit prescriptions using an electronic prescribing procedure. Oral prescriptions may be called in, but only in emergencies, and a written prescription must follow within 72 hours. Prescriptions for Schedule II drugs cannot be refilled. However, a DEA rule issued in 2007 now allows a prescriber to write multiple prescriptions on the same day—for the same patient and same drug—to be filled sequentially for up to a 90-day supply.
Schedules III and IV
Prescriptions for drugs in Schedules III and IV may be oral, written, or electronic. If authorized by the prescriber, these prescriptions may be refilled up to 5 times. Refills must be made within 6 months of the original order. If additional medication is needed beyond the amount provided for in the original prescription, a new prescription must be written.
Schedule V
The same regulations for prescribing drugs in Schedules III and IV apply to drugs in Schedule V. In addition, Schedule V drugs may be dispensed without a prescription provided the following conditions are met: (1) the drug is dispensed by a pharmacist; (2) the amount dispensed is very limited; (3) the recipient is at least 18 years old ; (4) the pharmacist writes and initials a record indicating the date, the name and amount of the drug, and the name and address of the recipient; and (5) state and local laws do not prohibit dispensing Schedule V drugs without a prescription.
Labeling
When drugs in Schedules II, III, and IV are dispensed, their containers must bear this label: Caution—Federal law prohibits the transfer of this drug to any person other than the patient for whom it was prescribed.
State Laws
All states have their own laws regulating drugs of abuse. In many cases, state laws are more stringent than federal laws. As a rule, whenever there is a difference between state and federal laws, the more restrictive of the two takes precedence.
