ADDICTION: CONCEPTS AND DEFINITIONS

This article deals with a number of concepts related to the basic nature of addiction, that are widely used but often misused, and that have undergone significant changes since the term addiction first came into the common vocabulary. In the following discussion, the terms are grouped according to themes, rather than being arranged in alphabetic order.

ABUSE AND MISUSE

In everyday English, abuse carries the connotations of improper, perverse, or corrupt use or practice, as in child abuse, or abuse of power. As applied to drugs, however, the term is difficult to define and carries different meanings in different contexts. In relation to therapeutic agents such as Benzondiazepines or Morphine, the term drug abuse is applied to their use for other than medical purposes, or in unnecessarily large quantities. With reference to licit but non-therapeutic substances such as Alcohol, it is understood to mean a level of use that is hazardous or damaging, either to the user or to others. When applied to illicit substances that have no recognized medical applications, such as Phencyclidine (PCP) or Mescaline, any use is generally regarded as abuse. The term misuse refers more narrowly to the use of a therapeutic drug in any way other than what is regarded as good medical practice.

Substance abuse means essentially the same as drug abuse, except that the term "substance" (shortened form of psychoactive substance) avoids any misunderstanding about the meaning of "drug". Many people regard as drugs only those compounds that are, or could be, used for the treatment of disease, whereas "substances" would also include materials such as organic solvents, Morning Glory Seeds or toad venoms, that have no medical applications at present but are "abused" in one or more of the senses defined above.

The best general definition of drug abuse is the use of any drug in a manner that deviates from the approved medical or social patterns within a given culture at a given time. This is probably the concept underlying the official acceptance of the term abuse in such instances as the names of the National Institute on Drug Abuse (USA) and the Canadian Centre on Substance Abuse. Such official acceptance, however, does not prevent the occurrence of ambiguities such as those mentioned in the next section.

RECREATIONAL OR CASUAL DRUG USE

These two terms are generally understood to refer to drug use that is small in amount, infrequent, and without adverse consequences, but these characteristics are not in fact necessary parts of the definitions. In the terminology recommended by the World Health Organization (WHO), the two terms are synonymous. However, recreational use really refers only to the motive for use, which is to obtain effects that the user regards as pleasurable or rewarding in some way, even if that use also carries some potential risks. Casual use refers to occasional as opposed to regular use, and therefore implies that the user is not dependent or addicted (see below), but it carries no necessary implications with respect to motive for use or the amount used on any occasion. Thus, a casual user might become intoxicated (see below) or suffer an acute adverse effect on occasions, even if these are infrequent.

Occasional use may also be circumstantial or utilitarian, if employed to achieve some specific short-term benefit under special circumstances. The use of Amphetamines to increase endurance and postpone fatigue by students studying for examinations, truck drivers on long hauls, athletes competing in endurance events, or military personnel on long missions, are all instances of such utilitarian use. Most observers also consider the first three of these to be abuse or misuse, but many would not regard the fourth example as abuse because it is or was prescribed by military authorities under unusual circumstances, for necessary combat goals. Nevertheless, in all four instances the same drug effect is sought for the same purpose (i.e., to increase endurance). This illustrates the complexities and ambiguities of definitions in the field of drug use.

INTOXICATION

This is the state of functional impairment resulting from the actions of a drug. It may be acute, i.e., caused by consumption of a high dose of drug on one occasion; it may be chronic, i.e., caused by repeated use of large enough doses to maintain an excessive drug concentration in the body over a long period of time. The characteristic pattern of intoxication varies from one drug to another, depending upon the mechanisms of action of the different substances. For example, intoxication by alcohol or barbiturates typically includes disturbances of neuromuscular coordination, speech, sensory functions, memory, reaction time, reflexes, judgment of speeds and distances, and appropriate control of emotional expression and behavior. In contrast, intoxication by amphetamine or cocaine usually includes raised blood pressure and heart rate, elevation of body temperature, intense hyperactivity, mental disturbances such as hallucinations and paranoid delusions, and sometimes convulsions. The term may be considered equivalent to overdosage, in that the signs of intoxication usually arise at higher doses than the pleasurable subjective effects for which the drug is usually taken.

HABIT AND HABITUATION

In everyday English, a habit is a customary behavior, especially one that has become largely automatic or unconscious as a result of frequent repetition of the same act. In itself, the word is simply descriptive, carrying no fixed connotation of good or bad. As applied to drug use, however, it is somewhat more judgmental. It refers to regular persistent use of a drug, in amounts that may create some risk for the user, and over which the user does not have complete voluntary control. Indeed, an alcohol habit has been defined in terms very similar to those used to define dependence (see below). In older writings, habit strength was used to characterize the degree of an individual's habitual drug use, in terms of the average amount of the drug taken daily. Reference to a drug habit implies that the drug use is the object of some concern on the part of the user or of the observer, but that it may not yet be sufficiently strongly established to make treatment clearly necessary.

Habituation refers either to the process of acquiring a drug habit, or to the state of the habitual user. Since habitual users frequently show increased tolerance (decreased sensitivity to the effects of the drug; see below), habituation is also used in the earlier literature to mean an acquired increase in tolerance. In its early reports, the World Health Organization Expert Committee on Drug Dependence (as it is now known, after several changes of name) used the term habituation to refer to a state arising from repeated drug use, that was less serious than addiction in the sense that it included only psychological and not physical dependence, and that harm, if it occurred, was only to the user and not to others. Drugs were classified according to whether they caused habituation or addiction. These distinctions were later recognized to be based on misconception, because (1) psychological (or psychic) dependence is even more important than physical dependence with respect to the genesis of addiction; (2) any drug that can damage the user is also capable of causing harm to others and to society at large; and (3) the same drug could cause effects that might be classed as "habituation" in one user and "addiction" in another. The WHO Expert Committee later recommended that both terms be dropped from use, and that dependence be used instead.

PROBLEM DRINKING

In an effort to avoid semantic arguments and value judgments about abuse or addiction, clinical and epidemiological researchers have increasingly made use of objective operational definitions and measures. Problem drinking is alcohol consumption at an average daily level that causes problems, regardless of whether these are of medical, legal, interpersonal, economic, or other nature, to the drinker or to others. The actual level, in milliliters of absolute alcohol per day, will obviously vary with the individual, the type of problem, and the circumstances. The advantage of this term is that a drinker who may not meet the criteria of dependence or who is reluctant to accept a diagnostic label of alcoholism or addiction can often be led to acknowledge that a problem exists and requires intervention.

ADDICTION AND DEPENDENCE

The term addiction was used in everyday and legal English long before its application to drug problems. In the sixteenth century it was used to designate the state of being legally bound or given over (e.g., bondage of a servant to a master) or, figuratively, of being habitually given over to some practice or habit; in both senses, it implied a loss of liberty of action. At the beginning of the twentieth century it came to be used more specifically for the state of being given over to the habitual excessive use of a drug, and the person who was "given over" to such drug use was described as an addict. By extension from the original meanings of addiction, drug addiction meant a practice of drug use that the user could not voluntarily cease, and loss of control over drinking was considered an essential feature of alcohol addiction. The emphasis was placed upon the degree to which the drug use dominated the person's life, in such forms as constant preoccupation with obtaining and using the drug, and inability to discontinue its use even when harmful effects made it necessary or strongly advisable to do so.

During the first half of the twentieth century, however, the pharmacological and social consequences of such use came increasingly to be the defining criteria. In 1957, the WHO Expert Committee defined addiction as "a state of periodic or chronic intoxication produced by the repeated consumption of a drug (natural or synthetic). Its characteristics include (1) an overpowering need (compulsion) to continue taking the drug and to obtain it by any means; (2) a tendency to increase the dose [later said to reflect tolerance]; (3) a psychic (psychological) and generally a physical dependence on the effects of the drug; and (4) detrimental effect on the individual and on society". Physical dependence is an altered physiological state arising from the regular heavy use of a drug, such that the body cannot function normally unless the drug is present. This state is recognizable only by the physical and mental disturbances that occur when drug use is abruptly discontinued or "withdrawn", and the constellation of these disturbances is known as a withdrawal syndrome. The specific pattern of the withdrawal syndrome varies according to the type of drug that has been used, and usually consists of changes opposite in direction to those originally produced by the action of the drug. For example, if opiate drugs cause constipation, their withdrawal typically produces diarrhea; if cocaine causes prolonged wakefulness and euphoria, the withdrawal syndrome will include profound sleepiness and depression; if alcohol decreases the reactivity of nerve cells, the withdrawal syndrome will include signs of over-reactivity, such as exaggerated reflexes or convulsions. In all cases, however, the withdrawal syndrome is quickly abolished by resumption of administration of the drug or of a substitute drug with a very similar pattern of actions.

It is now well recognized that a person can become physically dependent on a drug given in high doses for medical reasons (e.g., morphine given repeatedly for relief of chronic pain) and yet not show any subsequent tendency to seek and use the drug for non-medical purposes. The WHO Expert Committee therefore revised its definitions and concepts in 1973, substituting the single term dependence for the two terms addiction and habituation. Unfortunately, this change has not led to uniform terminology or concepts.

In essence, dependence is a state in which the individual can not function normally—physically, mentally or socially—in the absence of the drug. A simple definition given in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders published by the American Psychiatric Association (DSM-IV) includes only one fundamental element: compulsive use of the drug despite the occurrence of adverse consequences. However, a more detailed description of the dependence syndrome includes both physical components (increased tolerance to the drug; repeated experience of withdrawal symptoms; use of the drug to prevent or relieve withdrawal symptoms) and behavioral signs of loss of control over drug use (e.g., increasing prominence of drug-seeking behavior, even at the cost of disruption of other important parts of the user's daily life; use of larger amounts than intended; inability to cut down the amount used, despite persistent desire to do so; and awareness by the user of frequent craving.

Psychic dependence or psychological dependence refers to those components of the dependence syndrome other than tolerance and withdrawal symptoms, in particular the urgency of drug-seeking behavior, craving, inability to function in daily life without repeated use of the drug, and the inability to maintain prolonged abstinence. It has been attributed to a distress or tension, especially during periods of abstinence from the drug, that the user seeks to relieve by taking the drug again. This is, however, really a description, rather than an explanation.

Because of these differences in definition of dependence by different authorities, the term has proven to be less clear than intended, and has not displaced the term addiction from common use. The latter carries a clearer emphasis on the behavior of the individual, rather than the consequences of that behavior, as in the concept of nicotine addiction. A committee report of the Academy of Sciences of the Royal Society of Canada concluded that the only elements common to all definitions of addiction are a strongly established pattern of repeated self-administration of a drug in doses that reliably produce reinforcing psychoactive effects, and great difficulty in achieving voluntary long-term cessation of such use, even when the user is strongly motivated to stop.

REINFORCEMENT AND ITS RELATION TO DEPENDENCE

No drug can give rise to dependence unless (1) it produces some effect that causes the user to make efforts to obtain and use the drug again or (2) it is taken frequently enough to establish a strong pattern of drug-related behavior that is resistant to eradication. The effect that leads to repetition of drug-taking is a psychoactive effect, that is to say, an effect that alters the user's perceptions, thoughts and emotions in a manner that is usually (but not always) experienced as pleasurable or rewarding. The various drugs that are potentially abused or addictive are all thought to act in different ways to stimulate a common nerve-cell pathway originating in the midbrain and running to the base of the forebrain, where it releases the transmitter chemical dopamine. This pathway is often referred to in scientific shorthand as the reward system, though this is probably a misnomer. Activation of this pathway leads to an increased probability that the behavior that caused the activation (in this case, the drug-taking) will be repeated or reinforced, and the drug is called a reinforcer. A drug must have a reinforcing effect if it is to become addictive, but it is important to recognize that reinforcement is not the same as addiction. Reinforcement is an essential mechanism for survival, learning and adaptation. The satisfaction of thirst by drinking water, and of hunger by eating food, as well as the avoidance of harm by escape, are all examples of types of reinforcement by natural and necessary behaviors. Addictive drugs are regarded as "usurpers" of the reward system that produce reinforcement by direct drug action on it without serving any necessary biological function.

Nevertheless, drug-induced reinforcement, like reinforcement by food, water, sexual activity, or escape from harm, simply means that the behavior that caused it has an increased likelihood of being repeated. Some other process or processes must enter into play if that behavior is to become so strongly entrenched that it comes to dominate the individual's thinking and activities. Various hypotheses have been put forward concerning the nature of such additional processes. One suggestion is that activation of the reward system is controlled by something analogous to a thermostat, regulating the "set-point" of the system, and that frequent repetition of drug-taking leads to a change in set-point so that reinforcement grows progressively stronger over time. Another, perhaps related, hypothesis is that the degree of reinforcement by a given drug is regulated by genetic factors, and therefore vulnerability to addiction is greater in those who inherit either an abnormally high sensitivity to the reward system or a low sensitivity to the aversive (punishing, disagreeable) effects of the drug. Another view holds that the essential feature leading to addiction is not reward (i.e., pleasure or liking for the drug) but drug-induced sensitization of the process of incentive saliency (i.e., the subject's awareness of, and "wanting" for, drug-related stimuli becomes progressively greater, so that they have a steadily increased probability of controlling behavior). Yet another, and closely related, hypothesis is that drug-taking generally occurs within certain specific environmental or social contexts, and cues arising from these contexts can become linked to the drug effects as conditional stimuli, which then become able to elicit drug-taking behavior and further reinforcement. This is analogous to the role of the bell in Pavlov's experiments in which salivation, at first elicited by the feeding of meat to a dog, could eventually be elicited by the bell alone if the bell was always sounded just before the presentation of the meat. In this view, when the drug-taking comes under the control of such extraneous stimuli and is no longer a purely voluntary act, the transition to addiction has occurred. These various hypotheses, and possibly others, require much further research before the relation of reinforcement to addiction can be fully explained. Moreover, all such hypotheses must recognize that the degree of risk that any given individual will become addicted to a particular drug, even a strongly reinforcing one such as cocaine, is strongly influenced by environmental, social, economic and other factors.

CRAVING AND RELATED CONCEPTS

Craving refers to an intense desire for the drug, expressed as constant, obsessive thinking about the drug and its desired effects, a sense of acute deprivation that can be relieved only by taking the drug, and an urgent need to obtain it. This state is probably induced by exposure to bodily sensations and external stimuli that have in the past been linked to circumstances and situations in which drug use has been necessary, such as self-treatment of early withdrawal symptoms by taking more drug. Drug hunger is essentially synonymous with craving, and urge represents the same phenomenon but of lesser intensity.

The behavioral consequence of an urge or craving is usually a redirecting of the person's thoughts and activities towards obtaining and using a new supply of drug. All the behaviors directed toward this end, such as searching drawers and cupboards for possible remnants of drug, getting money (whether by legal or illegal means), contacting the sources of supply, purchasing the drug, and preparing it for use, are included under the term drug-seeking behavior. The more intense the craving, the more urgent, desperate, or irrational this behavior tends to become.

TOLERANCE AND SENSITIZATION

The term tolerance, which has long held a prominent place in the literature on drug dependence, has a number of different meanings. All of them relate to the degree of sensitivity or susceptibility of an individual to the effects of a drug. Initial tolerance refers to the degree of sensitivity or resistance displayed on the first exposure to the drug; it is expressed in terms of the degree of effect (as measured on some specified test) produced by a given dose of the drug, or by the concentration of drug in the body tissues or fluids resulting from that dose: the smaller the effect produced by that dose or concentration, the greater is the tolerance. Initial tolerance can vary markedly from one individual to another, or from one species to another, as a result of genetic differences, constitutional factors, or environmental circumstances.

The more frequent meaning of tolerance, however, is acquired tolerance (or acquired increase in tolerance )—increased resistance or decreased sensitivity to the drug as a result of adaptive changes produced in the body by previous exposure to that drug. This is expressed in terms of the degree of reduction in the magnitude of effect produced by the same dose or concentration, or (preferably) the increase in dose or concentration required to produce the same magnitude of effect. Acquired tolerance can be due to two quite different processes. Metabolic tolerance (also known as pharmacokinetic tolerance or dispositional tolerance ) is produced by an adaptive increase in the rate at which the drug is inactivated by metabolism in the liver and other tissues. This results in lower concentrations of drug in the body after the same dose, so that the effect is less intense and of shorter duration. Functional tolerance (also known as pharmacodynamic tolerance or tissue tolerance ) is produced by a decrease in the sensitivity of the tissues on which the drug acts, primarily the central nervous system, so that the same concentration of drug produces less effect than it did originally.

Acquired functional tolerance can occur in three different time frames. Acute tolerance is that which is displayed during the course of a single drug exposure, even the first time it is taken. As soon as the brain is exposed to the drug, compensatory changes begin to develop and become more marked as time passes. As a result, the degree of effect produced by the same concentration of drug is greater at the beginning of the exposure than it is in the later part; this phenomenon is sometimes called the Mellanby effect. A second time pattern of tolerance development is known in the experimental literature as rapid tolerance. This refers to an increased tolerance seen on the second exposure to the drug, if this occurs not more than one or two days after the first exposure. Chronic tolerance is that form of acquired tolerance that develops progressively over an extended period of time in which repeated exposure to the drug takes place. There is suggestive evidence that these three forms may involve the same or very similar mechanisms. All experimental interventions so far tested have produced virtually identical effects on rapid and chronic tolerance, and chronic tolerance is accompanied by an increase in the rate of development of acute tolerance.

Although acquired tolerance involves important physiological changes in the nervous system, it is also markedly influenced by learning. Tolerance develops much more rapidly if the individual is required to perform tasks under the influence of the drug, than if the same dose of the same drug is experienced without any performance requirement. Similarly, environmental stimuli that regularly accompany drug administration can come to serve as Pavlovian conditional stimuli that elicit tolerance as a conditional response, so that tolerance is demonstrated much more rapidly in the presence of these stimuli than in their absence.

Sensitization refers to a change opposite to tolerance, that occurs with respect to certain effects of a few drugs (most notably, central stimulant drugs such as cocaine and amphetamine, or low doses of alcohol that produce behavioral stimulation rather than sedation) when these are given repeatedly. The degree of effect produced by the same dose or concentration grows larger rather than smaller. For example, after repeated administration of amphetamine a dose that initially produced only a slight increase in physical activity can come to elicit very marked hyperactivity, and a convulsion can be produced by a dose that did not initially do so. This does not apply to all effects of the drug, however; tolerance can occur towards some effects (such as the inhibition of appetite) at the same time that sensitization develops to others. The reason for this difference is not yet known.

CROSS-TOLERANCE AND CROSS-DEPENDENCE

The term acquired tolerance is applied to tolerance developing to the actions of the same drug that has been administered repeatedly. However, if a second drug has actions similar to those of the first, an individual who becomes tolerant to the first drug is usually also tolerant to the second drug, even on the first occasion when the latter is used. This phenomenon is called cross-tolerance, and it may be partial or complete—it may extend to all the effects of the second drug, or only to some of them. The adaptive changes in the nervous system that give rise to acquired tolerance are believed by most researchers (though not all) to be responsible also for the development of physical dependence. Thus, an adaptive change in cell function, opposite in direction to the effect of the drug, will offset the latter when the drug is present (tolerance), but will give rise to a withdrawal sign or symptom when the drug is removed. The term neuroadaptive state has been proposed to designate all the physiological changes underlying the development of tolerance and physical dependence. If the second drug, to which cross-tolerance is present, is given during withdrawal from the first, it can prevent or suppress the withdrawal effect; this is known as cross-dependence. A related concept is that of transfer of dependence, from a first drug on which a person has become dependent to a second drug with similar effects, that has been given therapeutically to relieve the withdrawal signs produced by the first.

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Harold Kalant