Drugs, Addiction, and the Brain

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 Preface
Addiction is a brain disease that afflicts In this context, we have conceptualized addic-
­ illions of individuals, costs society enormously
m tion as a three-stage cycle – binge/intoxication,
in terms of medical and social expense, and withdrawal/negative affect, and preoccupation/
causes an untold amount of suffering among anticipation – that worsens over time and
those with the disease and their loved ones. One involves allostatic-like changes in the brain
of the most compelling arguments that addiction incentive salience, reward, stress, and execu-
is a biological disorder comes from advances in tive function systems. Allostasis is defined
our understanding of the brain in the context as stability with change and refers to a break
of addiction. The study of the neurobiology of with normal homeostatic processes that can
addiction has also taught us much about how lead to overt pathology and on the way gen-
the brain works, particularly in the domains of erate prolonged pathophysiology known as
reward, motivation, and emotions. addiction.
This textbook is an effort to bring the neuro- This book is divided into three major parts.
biology of addiction to a didactic level for uni- Chapters 1–3 outline basic information that the
versity and college students. We envision this reader will need to interpret and place in con-
book as serving as material for upper-division text the specific discussions of each major drug
college courses, Masters and Ph.D. graduate class. Chapter 1 defines the concept of addic-
programs, and seminars on the neurobiology tion from a historical perspective and includes
of addiction. We also envision this book as a discussions of the new diagnostic criteria
resource for those in the medical field, includ- defined by the American Psychiatric Associa-
ing pharmacists and addiction treatment tion’s Diagnostic and Statistical Manual of Men-
professionals, to help them to gain a basic tal Disorders, 5th edition (DSM-V). Chapter 2
understanding of the neurobiology of addic- defines basic neurobiological concepts relevant
tion. We are convinced that a better under- to addiction and provides an overall summary
standing of the disorder by both professionals of the neurobiology of addiction. Chapter 3
and patients will allow them to better under- outlines animal models of various aspects of
stand addiction processes and the challenges the addiction cycle and their reliability and
of recovery. validity.
The book is organized on the basis of con- Chapters 4–8 outline in detail the major
cepts that have guided our research in the field classes of drugs of abuse using a standard
for some time, but particularly the concept that format for each chapter: Definitions; History
addiction is a chronically relapsing disorder of Use; Use, Abuse and Addiction; Medical
characterized by: Uses; Behavioral and Physiological Effects;
(i) A compulsion to seek and take drugs, Pharmacokinetics; Behavioral Mechanism of
(ii) Loss of control over drug intake, and Action; and Neurobiological Effects divided
(iii) Emergence of a negative emotional state into the binge/intoxication, withdrawal/nega-
(e.g., dysphoria, anxiety, and irritability) tive affect, and preoccupation/anticipation stages.
that defines a motivational withdrawal The neurobiology section follows the out-
syndrome when access to the drug is line of the three stages of the addiction cycle
­prevented. so readers can explore the similarities and

vii
viii PREFACE

differences between each drug class. Each over 40 years of different but complementary
chapter includes a history of how the use of basic research from the Koob and Le Moal labo-
the drug evolved. In addition to the neurobio- ratories in the domains of the motivation and
logical mechanism of action, a section on the pathophysiology of motivation. Students will
behavioral mechanism of action is provided to receive a rich but catholic view of the neuro-
demonstrate a unifying and integrating princi- biology of addiction that will stimulate future
ple of order and predictability at the behavioral interest in the field and hopefully drive excite-
level for a given drug. Although the addiction ment to gain further knowledge.
process for each drug class has certain common
neurobiological elements, each class of drugs is
also unique and engages the addiction cycle at ACKNOWLEDGMENTS
different points.
Finally, the third section of the book, repre- All of the figures in this book were redrawn
sented by Chapter 9, is an attempt to translate from their original sources by Janet Hightower
the neurobiology of addiction to the realm of the of The Scripps Research Institute Biomedical
pharmacotherapeutic treatment of addiction. Graphics department. We are always grate-
This chapter explores the mechanisms of action ful for her efforts. We thank Lisa Romero for
of known approved treatments of addiction, assistance with proof processing. We would
again within the construct of the three stages of also like to extend our deep appreciation to
the addiction cycle. the following colleagues for providing encour-
We provide many opportunities for read- agement, suggestions, references, figures, and
ers to relate the concepts herein with the real their own personal interpretations: R. Adron
world of individuals with addiction by includ- Harris, Barbara Mason, Mandy McCracken,
ing various case histories and studies of addic- Elizabeth D’Amico, Joel Schlosburg, Ami
tion. We also provide references for the data Cohen, Tom Eissenberg, Scott Edwards, Ken
presented in the figures and tables and various Warren, Antonio Noronha, Olivier George, and
suggestions for further reading so that students Pietro Sanna.
may pursue certain topics of interest in more
depth. This book takes a unique approach to George F. Koob
the study of the neurobiology of addiction, Michael A. Arends
guided by a conceptual framework honed from Michel Le Moal
 C H A P T E R

1
What is Addiction?
O U T L I N E

Definitions of Addiction 1 Vulnerability to Addiction 11

Drug Use, Drug Abuse, and Drug Addiction 1
Neuroadaptational Views of Addiction 20
Diagnostic Criteria for Addiction 4
Behavioral Sensitization 20
Frequency and Cost of Addiction 5
Counteradaptation and Opponent Process 21
Patterns of Addiction 6
Motivational View of Addiction 22
The “Dependence” View of Addiction 7
Allostasis and Neuroadaptation 25
Psychiatric View of Addiction 8
Psychodynamic View of Addiction 8 Summary26
Social Psychological and Self-Regulation
Suggested Reading 27
Views of Addiction 11

DEFINITIONS OF ADDICTION drug use, the loss of control over limiting drug
intake, and the emergence of chronic compul-
Drug Use, Drug Abuse, and Drug sive drug seeking that characterize addiction.
Historically, three types of drug use have been
Addiction
delineated:
  
Drug addiction, formerly known as substance
1) O ccasional, controlled, or social use,
dependence (American Psychiatric Association,
2) Drug abuse or harmful use, and
1994), is a chronically relapsing disorder that is
3) Drug addiction as characterized as either
characterized by:
   Substance Dependence (Diagnostic and
1) A compulsion to seek and take a drug, Statistical Manual of Mental Disorders, 4th
2) Loss of control in limiting intake, and edition [DSM-IV]) or Dependence (see
3) Emergence of a negative emotional state below, and Tables 1.1 and 1.2).
  
(e.g., dysphoria, anxiety, irritability) when
More current descriptions have elaborated a
access to the drug is prevented.
   continuum of behavioral pathology, from drug
The occasional but limited use of an abus- use to addiction, in the context of substance use
able drug is clinically distinct from escalated disorders.

Drugs, Addiction, and the Brain

http://dx.doi.org/10.1016/B978-0-12-386937-1.00001-5 1 © 2014 Elsevier Inc. All rights reserved.
2 1. WHAT IS ADDICTION?

TABLE 1.1 DSM-5, DSM-IV, and ICD-10 Diagnostic Criteria for Abuse and Dependence
DSM-5 DSM-IV ICD-10

DEPENDENCE
A problematic pattern of substance use A maladaptive pattern of substance use, Three or more of the following have
leading to clinically significant impairment leading to clinically significant impairment been experienced or exhibited at
or distress, as manifested by at least two of the or distress as manifested by three or more of some time during the previous year
following occurring within a 12 month period the following occurring at any time in the
same 12-month period
1. Tolerance is defined by either of the 1. Need for markedly increased 1. Evidence of tolerance, such
following: a) a need for markedly amounts of a substance to achieve that increased doses are
increased amounts of substance to intoxication or desired effect; or required in order to achieve
achieve intoxication or desired effect markedly diminished effect with effects originally produced by
b) a markedly diminished effect with continued use of the same lower doses.
continued use of the same amount of amount of the substance.
substance.
2. Withdrawal is manifested by either of 2. The characteristic withdrawal 2. A physiological withdrawal
the following: a) the characteristic syndrome for a substance or use state when substance
withdrawal syndrome for substance or of a substance (or a closely related use has ceased or been
b) substance is taken to relieve or avoid substance) to relieve or avoid reduced as evidenced by:
withdrawal symptoms. withdrawal symptoms. the characteristic substance
withdrawal syndrome,
or use of substance (or a
closely related substance) to
relieve or avoid withdrawal
symptoms.
3. There is persistent desire or 3. Persistent desire or one or more 3. Difficulties in controlling
unsuccessful efforts to cut down or unsuccessful efforts to cut down or substance use in terms of
control substance use. control substance use. onset, termination, or levels
of use.
4. Substance is often taken in larger 4. Substance used in larger amounts or None
amounts or over a longer period than over a longer period than the person
was intended. intended.
5. Important social, occupational, or 5. Important social, occupational, or 4. Progressive neglect of
recreational activities are given up or recreational activities given up or alternative pleasures or
reduced because of substance use. reduced because of substance use. interests in favor of substance
use; or
6. A great deal of time is spent in 6. A great deal of time spent in   A great deal of time spent in
activities necessary to obtain activities necessary to obtain, to activities necessary to obtain,
substance, use substance, or recover use, or to recover from the effects of to use, or to recover from
from its effects. substance used. the effects of substance use.
7. Continued substance use despite 7. Continued substance use despite 5. Continued substance use
having persistent or recurrent social or knowledge of having a persistent or despite clear evidence of
interpersonal problems caused recurrent physical or psychological overtly harmful physical or
or exacerbated by the effects of problem that is likely to be caused or psychological consequences.
substance. exacerbated by use.
None None 6. A strong desire or sense of
compulsion to use
substance.

Continued
 Definitions of Addiction 3
TABLE 1.1 DSM-5, DSM-IV, and ICD-10 Diagnostic Criteria for Abuse and Dependence—cont’d
DSM-5 DSM-IV ICD-10

ABUSE
A maladaptive pattern of substance use A pattern of substance use that is
leading to clinically significant impairment causing damage to health.
or distress, as manifested by one (or more)
of the following occurring with a 12 month
period
8. Substance use is continued despite 1. Recurrent substance use resulting in The damage may be physical or
knowledge of having a persistent or a failure to fulfill major role mental. The diagnosis requires that
recurrent physical or psychological obligations at work, school, or home. actual damage should have been
problem that is likely to have been caused to the mental or physical
caused or exacerbated by substance health of the user
9. Recurrent use in situations in which it 2. Recurrent substance use in situations
is physically hazardous in which use is physically hazardous.
None 3. Recurrent substance-related legal
problems.
10. Recurrent substance use resulting in a 4. Continued substance use despite
failure to fulfill major role obligations having persistent or recurrent social
at work, school or home or interpersonal problems caused or
exacerbated by the effects of the drug.
11. Craving or a strong desire or urge to None None
use alcohol (or other substance)

TABLE 1.2 Estimated Number and Percentage of Persons of the US Population Aged 12 and Older (N = 258 Million)
Who Ever Used Alcohol, Tobacco, Cannabis, Cocaine, Heroin, or Prescription Opioids, the Number
and Percentage Who Used these Drugs in the Last Year, the Number and Percentage Who Ever Showed
Dependence (DSM-IV Criteria; See Text) in the Last Year, and the Number and Percentage Who Showed
Abuse or Dependence (DSM-5 Criteria; See Text) in the Last Year
Last-Year Use with Last-Year Use with
Ever Used Last-Year Use Dependence Abuse or Dependence
Drug Millions % Millions % Millions % Millions %

Cocaine 36.9 14.6 3.9 1.5 0.58 14.5 0.82 21.1

Stimulants 20.4 7.2 2.7 1.0 0.25 9.3 0.33 12.9

Methamphetamine 11.9 4.6 1.0 0.4 – – – –

Heroin 4.2 1.7 0.6 0.2 0.37 57.0 0.43 65.5

Analgesics 34.2 13.5 11.1 4.3 1.4 12.7 1.8 16.5

Alcohol 211.7 82.1 170.4 65.9 7.8 4.6 16.7 9.8

Tobacco 173.9 67.5 81.9 31.8 – – – –

Cigarettes* 161.8 62.8 67.1 26.1 22.9 34.2 22.9 34.2

Cannabis 107.8 42.0 29.7 11.5 2.6 8.8 4.2 13.9

* There is no abuse category for cigarettes, so the third and fourth columns of the table are identical.
Data from Substance Abuse and Mental Health Services Administration, National Survey on Drug Use and Health, 2011
4 1. WHAT IS ADDICTION?

Diagnostic Criteria for Addiction edition of the DSM (DSM-IV) and ICD-10, with
the exception of the removal of “committing
The diagnostic criteria for addiction, as illegal acts” and the addition of a new “craving”
described in the DSM, have evolved from the criterion. For example, rather than differentiat-
first edition published in 1952 to DSM-IV, with ing “alcoholics” and “alcohol abusers,” the new
a shift from an emphasis on the criteria of tol- classification Substance Use Disorder on Alco-
erance and withdrawal to other criteria which hol encompasses individuals who are afflicted
are more directed at compulsive use. The crite- by the disorder to different degrees, from “mild”
ria for Substance Use Disorders outlined in the (e.g., a typical college binge drinker who meets
DSM-IV closely resemble those outlined in the two criteria, such as alcohol is often taken in
­International Statistical Classification of Diseases larger amounts or over a longer period than
and Related Health Problems (ICD-10) for Drug was intended and there is a persistent desire or
Dependence (World Health Organization, 1992; unsuccessful efforts to cut down or control alco-
Table 1.1). The DSM-5 was published in 2013 hol use) to “severe” (e.g., a classic person with
(American Psychiatric Association, 2013). In alcoholism who meets six or more criteria, such
this, the criteria for drug addiction have changed as a great deal of time spent in activities neces-
both conceptually and diagnostically. The new sary to obtain alcohol, use alcohol, or recover
diagnostic criteria for addiction merge the abuse from its effects, recurrent alcohol use resulting in
and dependence constructs (i.e., substance a failure to fulfill major role obligations at work,
abuse and substance dependence) into one con- school, or home, alcohol use despite knowledge
tinuum that defines “substance use disorders” of having a persistent or recurrent physical or
on a range of severity, from mild to moderate to psychological problem, continued alcohol use
severe, based on the number of criteria that are despite persistent social or interpersonal prob-
met out of a total of 11. The severity of a sub- lems, tolerance, and withdrawal).
stance use disorder (addiction) depends on how The terms Substance Use Disorder and Addic-
many of the established criteria are met by an tion will be used interchangeably throughout
individual. Mild Substance Use Disorder is the this book to refer to a usage process that moves
presence of 2–3 criteria, moderate is 4–5 criteria, from drug use to addiction as defined above.
and severe is six or more criteria. These criteria Drug addiction is a disease and, more precisely,
remain basically the same as in the previous a chronic relapsing disease (Figures 1.1 and 1.2).

FIGURE 1.1 Last-year use with abuse or dependence (data from Substance Abuse and Mental Health Services Administration,
National Survey on Drug Use and Health, 2011; see Table 1.2).
 Definitions of Addiction 5
FIGURE 1.2 Stages of addiction to drugs
of abuse. Drug taking invariably begins with
social drug taking and acute reinforcement and
often, but not exclusively, moves in a pattern of
use from escalating compulsive use to depen-
dence, withdrawal, and protracted abstinence.
During withdrawal and protracted abstinence,
relapse to compulsive use is likely to occur
with a repeat of the cycle. Genetic factors, envi-
ronmental factors, stress, and conditioning all
contribute to the vulnerability to enter the cycle
of abuse/dependence and relapse within the
cycle. [Taken with permission from Koob GF, Le
Moal M. Neurobiology of Addiction. Academic
Press, London, 2006.]

The associated medical, social, and occupa- tobacco, 32% of the population used tobacco in the
tional difficulties that usually develop during last year. For cannabis, 13.9% of last-year users met
the course of addiction do not disappear after the criteria for Substance Abuse or Dependence on
detoxification. Addictive drugs produce changes cannabis. For cocaine, 21.1% of last-year users met
in brain circuits that endure long after the person the criteria for Substance Abuse or Dependence on
stops taking them. These prolonged neurochem- cocaine. For heroin, 65.5% of last-year users met
ical and neurocircuitry changes and the associ- the criteria for Substance Abuse or Dependence on
ated personal and social difficulties put former heroin.
patients at risk of relapse, a risk that is > 60% The cost to society of drug abuse and drug
within the first year after discharge. addiction is prodigious in terms of both the
direct costs and indirect costs associated with
secondary medical events, social problems, and
Frequency and Cost of Addiction loss of productivity. In the United States alone,
A shortcut for examining the frequency of sub- illicit drug use and addiction cost society $161
stance use disorders is to utilize a combination of billion per year in 2011. Alcoholism cost society
the percentage of individuals who have drug abuse $223 billion per year in 2012, and nicotine addic-
and drug dependence as defined by the DSM-IV, tion costs society $155 billion. In terms of health
since no data are yet available for the frequency of burden, alcohol and tobacco use are in the top 10
substance use disorders based on the DSM-5 cri- greatest risk factors for loss of years to disease
teria. Combining the old drug abuse and depen- and disability.
dence criteria yields an approximate percentage Much of the initial research into the neu-
of 15% (38.6 million people as of 2011) for the U.S. robiology of drug addiction focused on the
population who are 12 or older who suffered from acute impact of drugs of abuse (analogous to
Substance Use Disorders for alcohol, tobacco, or comparing no drug use to drug use). The focus
illicit drugs in the last year (Table 1.2). For alco- has shifted to chronic administration and the
hol, 9.8% of last-year users met the criteria for acute and long-term neuroadaptive changes
Substance Abuse or Dependence on Alcohol. For that occur in the brain. Sound arguments have
6 1. WHAT IS ADDICTION?

been made to support the hypothesis that drug taking, intense initial intoxication, the
addictions are similar to other chronic relaps- development of profound tolerance, escalation
ing disorders, such as diabetes, asthma, and in intake, and profound dysphoria, physical dis-
hypertension, in their chronic relapsing nature comfort, and somatic withdrawal signs during
and treatment efficacy (for further reading, see abstinence (Box 1.1). Intense preoccupation with
McLellan et al., 2000). Current neuroscientific obtaining opioids (craving) develops and often
drug abuse research seeks to understand the precedes the somatic signs of withdrawal. This
cellular and molecular mechanisms that medi- preoccupation is linked to stimuli associated
ate the transition from occasional, controlled with obtaining the drug, stimuli associated with
drug use to the loss of behavioral control over withdrawal, and internal and external states of
drug seeking and drug taking that defines stress. A pattern develops in which the drug
chronic addiction. must be administered to avoid the severe dys-
phoria and discomfort of abstinence.
Alcohol substance use disorder or alco-
Patterns of Addiction holism follows a somewhat different pattern
Different drugs produce different patterns of of drug taking that depends on the sever-
addiction, with an emphasis on different com- ity of the disorder. The initial intoxication is
ponents of the addiction cycle. Opioids are a less intense than opioids, and the pattern of
classic drug of addiction, in which an evolving drug taking often is characterized by binges
pattern of use includes intravenous or smoked of alcohol intake that can be daily episodes or

BOX 1.1

Jimmy pulls out of the graveled driveway she probably is going to the next group session.
onto the smooth asphalt surface of the road. It Dennis’ heart begins to pound – gripped by a
feels so good to drive again after the long months flood of memories about the car, where he and
in “rehab.” No heroin use in over 6 months. ‘‘Not Diana had shared so much cocaine. A wave of
bad,” he congratulates himself. But as he takes intense feeling rushes from the tip of his toes,
the exit to the old neighborhood, his bowels up to his head and back down again. Thoughts
begin to growl. He breaks out in sweat, gripping racing, desire coursing through his body, he
the steering wheel and trying to ignore the raw, turns away from the road home, into the night.
acid taste in the back of his throat. Yawning, eyes As he approaches the familiar buying corner, he
watering, he feels mounting panic, and the desire can taste the cocaine in the back of his throat.
for drugs begins to burn in the pit of his stomach, He is sweating heavily now, ears ringing. “Just
“So much for good intentions,” be mutters, turn- a taste,” he bargains with himself, “just a taste is
ing toward a familiar alley and the drug that will all I’m going to buy.”
make everything right again.
Dennis leaves his cocaine therapy group From: Childress AR, Hole AV, Ehrman RN, Robbins SJ,
McLellan AT, O’Brien CP, Cue reactivity and cue reactivity
full of energy. “I’ve got 30 days clean, and now interventions in drug dependence. In: Onken LS, Blaine JD,
I’m going for 90!” he yells to a buddy as they Boren JJ (Eds.), Behavioral Treatments for Drug Abuse and
enter their cars. As he leaves the parking lot, a Dependence (series title: NIDA Research Monograph, vol.
137), National Institute on Drug Abuse, Rockville MD, 1993,
familiar white sedan is pulling in – Diana’s car; pp. 73–95.
 Definitions of Addiction 7
prolonged days of heavy drinking. A binge is craving has been less studied to date, it is most
currently defined by the US National Institute likely linked to both cues and internal states
on Alcohol Abuse and Alcoholism as consum- often associated with negative emotional states
ing five standard drinks for males and four and stress, similarly to other drugs of abuse.
standard drinks for females in a two hour
period, or obtaining a blood alcohol level of
0.08 gram percent. Alcoholism is character- The “Dependence” View of Addiction
ized by a severe emotional and somatic with-
The term “dependence” within the concep-
drawal syndrome and intense craving for the
tual framework of addiction has a confused his-
drug that is often driven by negative emo-
tory. However, discussing the evolution of the
tional states but also by positive emotional
term is instructive. Historically, definitions of
states. Many individuals with alcoholism con-
addiction began with definitions of dependence.
tinue with such a binge/withdrawal pattern
Himmelsbach defined physical dependence as:
for extended periods; for others, the pattern
evolves into opioid-like addiction, in which “...an arbitrary term used to denote the presence
they must have alcohol available at all times of an acquired abnormal state wherein the regular
to avoid the consequences of abstinence. administration of adequate amounts of a drug has,
Tobacco addiction contrasts with the above through previous prolonged use, become requisite to
physiologic equilibrium. Since it is not yet possible
patterns. Tobacco is associated with virtually no
to diagnose physical dependence objectively with-
binge-like behavior in the binge/intoxication stage out withholding drugs, the sine qua non of physical
of the addiction cycle. Cigarette smokers who met dependence remains the demonstration of a charac-
the criteria for substance dependence or depen- teristic abstinence syndrome.”
dence under the DSM-IV and ICD 10 criteria are (Himmelsbach CK. Can the euphoric, analgetic, and
likely to smoke throughout their waking hours physical dependence effects of drugs be separated? IV. With
reference to physical dependence. Federation Proceed-
and experience negative emotional states (dys- ings, ­1943, (2), 201–203).
phoria, irritability, and intense craving) during
abstinence. The pattern of intake is one of highly This definition eventually evolved into the
titrated intake of the drug during waking hours. definition for physical dependence: “intense
Psychostimulants, such as cocaine and physical disturbances when the administration of
amphetamines, show a pattern that has a greater a drug is suspended” (Eddy NB, Halbach H, Isbell
emphasis on the binge/intoxication stage. Such H, Seevers MH. Drug dependence: its significance
binges can last hours or days, often followed by and characteristics. Bulletin of the World Health
a crash that is characterized by extreme dyspho- Organization, 1965, (32), 721–733). However, this
ria and inactivity. Intense craving and anxiety terminology clearly did not capture many of the
occur later and are driven by both environmen- aspects of an addictive process that do not show
tal cues that signify the availability of the drug, physical signs, necessitating the creation of the
and internal states that are often linked to nega- term psychic dependence to capture the behavioral
tive emotional states and stress. aspects of the symptoms of addiction:
Marijuana substance use disorder follows
a pattern similar to opioids and tobacco, with “A condition in which a drug produces ‘a feeling
a significant intoxication stage. As chronic use of satisfaction and a psychic drive that require peri-
odic or continuous administration of the drug to pro-
continues, subjects begin to show a pattern of
duce pleasure or to avoid discomfort’…”
chronic intoxication during waking hours. With- (Eddy NB, Halbach H, Isbell H, Seevers MH. Drug
drawal is characterized by dysphoria, irritabil- ­dependence: its significance and characteristics. Bulletin of
ity, and sleep disturbances. Although marijuana the World Health Orgaization, 1965, (32), 721–733).
8 1. WHAT IS ADDICTION?

Later definitions of addiction resembled a symptoms will be considered equivalent to

combination of physical and psychic depen- “addiction” remains to be determined.
dence, with more of an emphasis on the psychic
or motivational aspects of withdrawal, rather Psychiatric View of Addiction
than on the physical symptoms of withdrawal:
From a psychiatric perspective, drug addiction
“Addiction; from the Latin verb ‘addicere,’ to give has aspects of both impulse control disorders and
or bind a person to one thing or another. Generally compulsive disorders. Impulse control disorders
used in the drug field to refer to chronic, compulsive,
are characterized by an increasing sense of ten-
or uncontrollable drug use, to the extent that a person
(referred to as an ‘addict’) cannot or will not stop the sion or arousal before committing an impulsive
use of some drugs. It usually implies a strong (Psy- act, pleasure, gratification, or relief at the time of
chological) Dependence and (Physical) Dependence committing the act, and regret, self-reproach, or
resulting in a Withdrawal Syndrome when use of guilt following the act (see early versions of the
the drug is stopped. Many definitions place primary
DSM of the American Psychiatric Association). In
stress on psychological factors, such as loss of self-
control and overpowering desires; i.e., addiction is contrast, compulsive disorders are characterized
any state in which one craves the use of a drug and by anxiety and stress before committing a com-
uses it frequently. Others use the term as a synonym pulsive repetitive behavior and relief from the
for physiological dependence; still others see it as a stress by performing the compulsive behavior.
combination (of the two).”
As an individual moves from an impulsive disor-
(Nelson JE, Pearson HW, Sayers M, Glynn TJ
(eds.) Guide to Drug Abuse Research Terminol- der to a compulsive disorder, a shift occurs from
ogy. ­National Institute on Drug Abuse, Rockville MD, positive reinforcement to negative reinforcement
1982). that drives the motivated behavior (Figure 1.3).
Drug addiction progresses from impulsivity to
Unfortunately, the word dependence in this compulsivity in a collapsed cycle of addiction
process has multiple meanings. Any drug can that consists of three stages: preoccupation/antici-
produce dependence if dependence is defined pation, binge/intoxication, and withdrawal/nega-
as the manifestation of a withdrawal syndrome tive affect. Different theoretical perspectives from
upon the cessation of drug use, see above. experimental psychology, social psychology, and
Meeting the ICD-10 criteria for Dependence or neurobiology can be superimposed on these
the DSM-5 criteria for Substance Use Disorder three stages, which are conceptualized as feeding
requires much more than simply manifesting into each other, becoming more intense, and ulti-
a withdrawal syndrome. For the purposes of mately leading to the pathological state known
this book, dependence (with a lowercase “d”) as addiction (Figure 1.4; for further reading, see
will refer to the manifestation of a withdrawal Koob and Le Moal, 1997).
syndrome, and addiction will refer to Depen-
dence as defined by the ICD-10. The terms
Dependence (with a capital “D”), addiction, and Psychodynamic View of Addiction
alcoholism will be held equivalent for this book. A psychodynamic view of addiction that inte-
The term Substance Use Disorder is defined as grates the neurobiology of addiction was elabo-
a problematic pattern of drug use that leads to rated by Khantzian and colleagues (for further
clinically significant impairment or distress, reading, see Khantzian, 1997) with a focus on the
reflected by at least two the 11 criteria within factors that produce vulnerability to addiction.
a 12 month period (see above). How this clus- This perspective is deeply rooted in the psycho-
ter of cognitive, behavioral, and physiological dynamic aspects of clinical practice developed
 Definitions of Addiction 9

FIGURE 1.3 Diagram showing stages of impulse control disorder and compulsive disorder cycles related to the sources
of reinforcement. In impulse control disorders, increasing tension and arousal occur before the impulsive act, with pleasure,
gratification or relief during the act, and regret or guilt following the act. In compulsive disorders, recurrent and persistent
thoughts (obsessions) cause marked anxiety and stress followed by repetitive behaviors (compulsions) that are aimed at pre-
venting or reducing distress. Positive reinforcement (pleasure/gratification) is more closely associated with impulse control
disorders. Negative reinforcement (relief of anxiety or relief of stress) is more closely associated with compulsive disorders.
[Taken with permission from Koob GF. Allostatic view of motivation: implications for psychopathology. In: Bevins RA, Bardo MT (eds.)
Motivational Factors in the Etiology of Drug Abuse (series title: Nebraska Symposium on Motivation, vol 50). University of
Nebraska Press, Lincoln NE, 2004, pp. 1–18.]

from a contemporary perspective with regard overwhelming and unbearable and may consist of
to substance use disorders. The focus of this an affective life that is absent and nameless. From
approach is on developmental difficulties, emo- this perspective, drug addiction is viewed as an
tional disturbances, structural (ego) factors, per- attempt to medicate such a dysregulated affective
sonality organization, and the building of the state. Patient suffering is deeply rooted in disor-
“self.” dered emotions, characterized at their extremes
Two critical elements (disordered emotions by unbearable painful affect or a painful sense
and disordered self-care) and two contributory of emptiness. Others cannot express personal
elements (disordered self-esteem and disordered feelings or cannot access emotions and may suf-
relationships) were identified. These evolved into fer from alexithymia, defined as “a marked diffi-
a self-medication hypothesis, in which individu- culty to use appropriate language to express and
als with substance use disorders take drugs as a describe feelings and to differentiate them from
means to cope with painful and threatening emo- bodily sensation” (Sifneos PE. Alexithymia, clinical
tions. In this conceptualization, individuals with issues, politics and crime. Psychotherapy and Psy-
addiction experience states of subjective distress chosomatics, 2000, (69) 113–116).
and suffering that may or may not be sufficient in Such self-medication may be drug-specific.
meeting DSM-5 criteria for a psychiatric diagnosis. Patients may preferentially use drugs that fit the
Individuals with addiction have feelings that are nature of their painful affective states. Opiates
10 1. WHAT IS ADDICTION?

FIGURE 1.4 Diagram describing the spiraling distress/addiction cycle from four conceptual perspectives: social psy-
chological, psychiatric, dysadaptational, and neurobiological. Notice that the addiction cycle is conceptualized as a spiral
that increases in amplitude with repeated experience, ultimately resulting in the pathological state known as addiction. (A)
The three major components of the addiction cycle – preoccupation/anticipation, binge/intoxication, and withdrawal/negative affect –
and some of the sources of potential self-regulation failure in the form of underregulation and misregulation. (B) The same
three major components of the addiction cycle with the different criteria for substance dependence incorporated from the
DSM-IV. (C) The places of emphasis for the theoretical constructs of sensitization and counteradaptation. (D) The hypotheti-
cal role of different neurochemical and endocrine systems in the addiction cycle. Small arrows refer to increased or decreased
functional activity. DA, dopamine; CRF, corticotropin-releasing factor. [Taken with permission from Koob GF, Le Moal M. Drug
abuse: hedonic homeostatic dysregulation. Science, 1997, (278), 52–58.]

might effectively reduce psychopathological The Analysis of the Self: A Systematic Approach
states of violent anger or rage. Others who suffer to the Psychoanalytic Treatment of Narcissistic
from hypohedonia, anergia, or lack of feelings Personality Disorders [series title: The Psychoan-
might prefer the activating properties of psycho- alytic Study of the Child, vol 4]. International Uni-
stimulants. Still others who sense themselves as versities Press, New York, 1971). The paradox is
being flooded by their feelings, or cut off from that using drugs to self-medicate emotional pain
their feelings entirely, may opt for repeated will eventually perpetuate it by perpetuating a
moderate doses of alcohol or depressants in a life that revolves around drugs.
medicinal effort to express feelings that they are Self-care deficits reflect an inability to ensure
unable to communicate. The common element of one’s self-preservation and are characterized
the self-medication hypothesis is that each drug by an inability to anticipate or avoid harmful
class serves as an antidote or “replacement for a or d­ angerous situations and an inability to use
defect in the psychological structure” (Kohut H. appropriate judgment and feeling as guides
 Definitions of Addiction 11
in the face of adversity. Thus, self-care deficits where each violation brings additional negative
reflect an inability to appropriately experience affect, resulting in spiraling distress. For exam-
emotions and fully recognize the consequences of ple, a failure of strength may lead to initial drug
dangerous behaviors. Disordered self-care com- use or relapse, and other self-regulation failures
bines with a disordered emotional life to become can be recruited to provide entry into or prevent
a principal determinant of substance use disor- exit from the addiction cycle (Box 1.3).
ders. The core element of this psychodynamic At the neurobehavioral level, such dysregu-
perspective is a dysregulated emotional system lation may be reflected by deficits in informa-
in individuals who are vulnerable to addiction. tion-processing, attention, planning, reasoning,
This psychodynamic approach integrates self-monitoring, inhibition, and self-regulation,
well with the critical role of dysregulated brain many of which involve functioning of the frontal
reward and stress systems that are revealed by lobe. Executive function deficits, self-regulation
studies of the neurobiology of addiction. From problems, and frontal lobe dysfunction or pathol-
a neurobiological perspective, additional harm ogy constitute risk factors for biobehavioral dis-
to the personality can by produced by the direct orders, including drug abuse. Deficits in frontal
effects of the drugs themselves, thus perpetuat- cortex regulation in children or young adoles-
ing or actually creating such character flaws. cents predict later drug and alcohol consump-
tion, especially in children raised in families with
histories of drug and biobehavioral problems.
Social Psychological and Self-Regulation
Views of Addiction
Vulnerability to Addiction
At the social psychology level, failures in
self-regulation have been argued to be the root A wide range of factors may predispose indi-
of major social pathologies (for further read- viduals to addiction, many of which provide
ing, see Baumeister et al., 1994). Important insights into the etiology of the disorder. These
self-regulation elements are involved in differ- include comorbidity with other psychiatric dis-
ent stages of addiction, including other patho- orders, including anxiety, affective, personality,
logical behaviors, such as compulsive gambling and psychotic disorders, and neurobehavioral
and binge eating. Failures in self-regulation can traits, such as impulsivity, development (ado-
lead to addiction in the case of drug use or an lescence), psychosocial stress, and gender (see
addiction-like pattern with nondrug behaviors. Table 1.3). The neurobiological differences in
Underregulation, reflected by strength defi- predisposing factors which are common to the
cits, a failure to establish standards, conflicting neurobiological changes associated with addic-
standards, attentional failures, and misregula- tion provide insights into the neuropathology
tion (misdirected attempts to self-regulate) can associated with the development of addiction.
contribute to the development of addiction- Individual differences in temperament, social
like behavioral patterns (Figure 1.4, Box 1.2). development, comorbidity, protective factors,
The transition to addiction can be facilitated and genetics are areas of intense research, and
by lapse-activated causal patterns (patterns of a detailed discussion of these contributions
behavior that contribute to the transition from to addiction is beyond the scope of this book.
an initial lapse in self-regulation to a large-scale Each of these factors presumably interacts with
breakdown), thus leading to spiraling distress. the neurobiological processes discussed in this
In some cases, the first self-regulation failure can book. A reasonable assertion is that the ini-
lead to emotional distress, setting the stage for tiation of drug abuse is more associated with
a cycle of repeated failures to self-regulate and social and environmental factors, whereas the
12 1. WHAT IS ADDICTION?

BOX 1.2

When Heather Brooks entered high school the more she smoked, the more outrageously
in 1991, her guidance counselor pegged her as fabulous she felt.
someone with high potential. In her first semes- As Heather’s freshman year – and her use
ter, she earned top grades, She participated in of marijuana – progressed, pot was no longer
many extracurricular activities. just a social drug. First thing in the morning,
A student of classical piano, Heather filled her she smoked a joint to get herself out of bed. She
family’s suburban Chicago home with Chopin smoked in a friend’s car on the way to school.
and Beethoven. Between classes she smoked in the bathroom.
During her freshman year, 14-year-old Heather She was even stoned when she sang in a school
made friends with some older kids, and her life choir concert.
took a sudden turn. One evening while she was To achieve a high, meanwhile, required ever
with them in a neighborhood park, a tall, good- increasing amounts of the substance. She gradu-
looking junior handed her a marijuana cigarette. ated to using a bong, or water pipe, which con-
“Take a drag,” he urged, “it’ll mellow you out.” centrates the smoke inside a chamber so none is
At first Heather held off. She’d always disap- lost into the air. "The only thing wasted," a bong
proved of drugs. But Justin reassured her. “It’s purveyor promised, “is you.”
not a drug,” he said, “it’s only pot.” Heather didn’t worry that she needed more
Heather decided to give it a try. "Okay," she and more of the stuff. To her, this was a sign of
conceded, “just one puff.” prowess. “Look how much I can smoke and not
With instructions from her friends, she pulled get loaded,” she bragged. And she downplayed
the sweet-smelling smoke into her lungs and thoughts of addiction. Pot, her friends kept
held it there until she thought she’d burst. Then reminding her, wasn’t any more habit-forming
came more puffs. As she blew out the wispy than milk. She was sure she could quit any time.
­remnants of smoke, she felt dizzy – and euphoric. When Heather’s parents asked how school
"Give me another drag,” she begged, tugging on was going, she always flashed a big smile.
Justin’s arm. “Everything’s fine,” she’d say. Because she’d
After a few more drags on the joint, Heather always been such a good daughter, Frank and
felt a deepening glow of contentment. Time Diana Brooks had every reason to believe her.
slowed to a crawl. Colors and sounds seemed Gradually, though, Heather had become a highly
more intense. “Wow!” she thought, “This stuff is accomplished liar.
fantastic!”. “I’ll be at Amy’s house after school,” she said
Her high lasted four hours. Heather couldn’t one morning, looking her mother squarely in the
wait for the next invitation from her new friends. eye. Instead, Heather drove with her friends to a
Because she’d taken the big step and smoked a dead-end dirt road where they smoked pot until
joint, she felt a strong bond with them. She was it was time to go home for dinner.
confident someone would bring more pot to On Friday nights, Heather came home
share. promptly at her eleven o’clock curfew and said
She wasn’t disappointed. The next weekend, good-night to her parents. After the sliver of light
when Justin offered her a joint, Heather took it under their door went out, she waited ten min-
eagerly. “Why do adults get so bent cut of shape over utes, then tiptoed downstairs and slipped out the
a little pot?” she wondered. All she knew was that door to go party.

     
 Definitions of Addiction 13

BOX 1.2 (cont’d)

When Heather’s gang smoked pot, they also smell of pot in her room, she stuffed an empty
always drank – beer or tumblers of vodka and paper-towel roll with a sheet of fabric softener
cranberry juice. The alcohol made Heather feel and exhaled into the tube. She carried eye drops
more mellow than ever. It also amazed her how to clear up bloodshot eyes. Before heading home,
much she could drink without ever getting sick. she gargled with mouthwash or chewed cinna-
At school Heather’s absences began to mount mon-flavored gum. Often she brought a clean
and her grades took a nose dive. Yet for a while shirt to a party and left the smoke saturated one
she continued to fool her parents. When report behind.
cards were mailed, she intercepted them at home As Heather’s pot intake increased, she
and, with skillful use of correction fluid and a wanted even more. Encouraged by her friends,
photocopying machine, turned Ds and Fs to As she experimented with a variety of mind-alter-
and Bs. She even added some nice comments: ing substances: LSD, mescaline, crack, codeine,
“Heather is a pleasure to have in class,” she cocaine and amphetamines. Through it all, how-
wrote, imitating the handwriting of one of her ever, marijuana remained her “drug of choice.”
teachers. It was what she started out with, and what she
By the end of Heather’s freshman year, her ended up with.
grade-point average had plummeted from 4.0 to One warm night toward the end of Heather’s
1.2, and she’d tallied up a staggering 39 absences. sophomore year, she attended what had become
Meanwhile, Heather dropped many of a typical party for her: the host’s parents were
her extracurricular activities. When her par- away, and there was plenty of liquor along with
ents asked why, she said she just needed some a variety of drugs. Heather wasn’t supposed to
“space.” Diana and Frank Brooks pinned this on be there. Through conferences with her guidance
normal teenage turmoil. counselor, her parents had found out about her
By now, Heather no longer cared about any- doctored grades and her frequent absences. They
one or anything – except her next high. Her drive now suspected alcohol or drugs and grounded
and motivation were gone, replaced by total her. But that evening her parents had gone out.
apathy. Heather figured she could slip out and be back
Drugs had become her life. She couldn’t stop. before they returned.
In her journal she wrote: “Pot is a motionless sea Around 10 p.m., she hopped in the back seat
of destruction. I’m drowning.” of a car with four others for a ride home. Ryan,
Indeed, always in excellent health, Heather the driver, was both drunk and stoned. As he
now felt sick much of the time. Her hands and stomped on the accelerator on a straight stretch
feet were constantly cold. She woke up coughing of highway, Heather saw the speedometer pass
and pushed her face deep into her pillow so her 100 m.p.h.
parents wouldn’t hear her. She also noticed that Moments later, the car slammed into a guard-
her menstrual cycle had become irregular. rail, rolled down an embankment and came to
Heather’s parents saw the changes in their rest on its roof. Miraculously, everyone survived.
daughter. But their questions turned up noth- Ryan’s face was jammed onto the steering-wheel
ing, and they were worried. By her sophomore horn, which blared loudly. Others bled from
year, Heather knew all the tricks. To hide the their faces and dangled broken limbs. Numbed

Continued

     
14 1. WHAT IS ADDICTION?

BOX 1.2 (cont’d)

by alcohol, marijuana and cocaine, Heather was into anguished cries. This was the wake-up call
oblivious of her own injuries as she helped one of that Heather had long needed – and her parents
her friends from the tangled wreck. too. “You’ve hit rock bottom,” Frank told his
Heather had suffered severe injuries to her daughter later, “we’re still your best friends – but
back and neck, and would need a year of physi- we’re going to be watching you every minute.”
cal therapy. Each morning, Frank Brooks waited to leave
“I didn’t know Ryan had been drinking,” for work until Heather was on her bus. When she
Heather lied to her parents. They wanted desper- returned, a parent was waiting for her. No more
ately to believe her. Relieved that she was alive, rides with friends. No more parties.
they forgave her “just this once” for sneaking That summer, her parents took her to a La
out. From then on, they warned, they were tight- Jolla, Calif., beach house to get her away from
ening their watch. But while she recuperated at her “friends.” For four full weeks, Heather was
home, Heather smoked pot secretly. shaky, nervous and sweaty as her body adjusted
Heather had been dating Charlie Evans. He to a healthier lifestyle. She had so much difficulty
was handsome, athletic and popular with the girls. adapting to any kind of schedule that she wasn’t
He was also heavily into marijuana and cocaine. sure when to eat or sleep. Slowly, however, her
One evening three months after her accident, numbed brain began to function. Frequently, she
Charlie appeared at the front door with an eight- thought about the time she spent in the hospital: “I
ball of cocaine (about an eighth of an ounce). Her almost died, and none of my friends even came to visit.”
parents were out to dinner. Soon Heather and Char- Returning to Chicago, Heather was as deter-
lie were sniffing the white powder through straws. mined to turn her life around as she once seemed
After several lines, her heart began to race, determined to destroy it. She doubled up on
something that had never happened before. She courses she had failed as a sophomore. The
smoked a few joints to “mellow out,” but instead sounds of her piano once again filled the Brooks
she became more jumpy. Looking down, she saw home.
her shirt move with the heavy pounding of her As a senior, Heather traveled to Europe with
heart. Terrified, she told Charlie to call for help. the school choir. As she stood in an ancient
He dialed 911. “Send someone quick,” he yelled. cathedral, her soprano voice joining the others,
He didn’t wait around. “I’ve got to split before the she recalled the concert when she’d shown up
cops get here,” he said, going out the back door. stoned.
En route to the hospital, Heather’s heart rate “Just three years ago,” she thought, “What a dif-
soared to 196 beats a minute. “Talk to us,” a para- ferent person I am now.”
medic urged, “we don’t want to lose you.” Find-
ing Heather in intensive care and learning that From: Ola P, D’Aulaire E. Here’s what marijuana can do inside
a teenager’s body: “But It’s Only Pot.” Reader’s Digest, 1997,
she’d overdosed on cocaine, Diana Brooks broke Jan:83–89.

progression to a substance use disorder (addic- identified as vulnerability factors, including

tion) is more associated with neurobiological impulsivity, novelty- and sensation-seeking,
factors. Temperament and personality traits conduct disorder, and negative affect. From the
and some temperament clusters have been perspective of comorbid psychiatric disorders,
 Definitions of Addiction 15

BOX 1.3

We head north to the cabin. Along the way I I turn and I leave their room and I close their
learn that my parents, who live in Tokyo, have door and I go to the kitchen. I look through the
been in the States for the last two weeks on busi- cabinets and I find an unopened half-gallon bot-
ness. At four a.m. they received a call from a tle of whiskey. The first sip brings my stomach
friend of mine who was with me at a hospital and back up, but after that it’s all right. I go to my
had tracked them down in a hotel in Michigan. room and I drink and I smoke some cigarettes
He told them that I had fallen face first down a and I think about her. I drink and I smoke and
fire escape and that he thought they should find I think about her and at a certain point blackness
me some help. He didn’t know what I was on, comes and my memory fails me.
but he knew there was a lot of it and he knew it Back in the car with a headache and bad
was bad. They had driven to Chicago during the breath. We’re heading north and west to Minne-
night. sota. My Father made some calls and got me into
We drive on and after a few hard silent min- a clinic and I don’t have any other options, so
utes we arrive. We get out of the car and we go I agree to spend some time there and for now I’m
into the house and I take a shower because I need fine with it. It’s getting colder.
it. When I get out there are some fresh clothes sit- I want to run or die or get fucked up. I want
ting on my bed. I put them on and I go to my to he blind and dumb and have no heart. I want
parents’ room. They are up drinking coffee and to crawl in a hole and never come out. I want to
talking but when I come in they stop. wipe my existence straight off the map. Straight
“Hi.” off the fucking map. I take a deep breath.
Mom starts crying again and she looks away. We enter a small waiting room.
Dad looks at me. They’re gonna check you in now.
“Feeling better?” We stand and we move toward a small room
“No.” where a man sits behind a desk with a computer.
“You should get some sleep.” He meets us at the door.
“I’m gonna.” “You ready to get started?”
“Good.” I don’t smile.
I look at my Mom. She can’t look back. “Sure.”
I breathe. He gets up and I get up and we walk down a
“I just.” hall. He talks and I don’t. “The doors are always
I look away. open here, so if you want to leave, you can. Sub-
“I just, you know.” stance use is not allowed and if you’re caught
I look away. I can’t look at them. using or possessing, you will be sent home. You
“I just wanted to say thanks for picking me are not allowed to say anything more than hello
up.” to any women aside from doctors, nurses, or staff
Dad smiles. He takes my Mother by the hand members. If you violate this rule, you will be sent
and they stand and they come over to me and home. There are other rules, but those are the
they give me a hug. I don’t like it when they only ones you need to know right now.”
touch me so I pull away. We walk through a door into the medical
“Good night.” wing. There are small rooms and doctors and
“Good night, James. We love you.” nurses and a pharmacy. The cabinets have large

Continued
16 1. WHAT IS ADDICTION?

BOX 1.3 (cont’d)

steel locks. He shows me to a room. It has a bed “Do you use anything else?”
and a desk and a chair and a closet and a win- “Cocaine.”
dow. Everything is white. “How often?”
He stands at the door and I sit on the bed. “‘Every day.”
“A nurse will be here in a few minutes to talk She marks it down.
with you.” “How much?”
“‘Fine.” “As much as I can.”
“You feel okay?” She marks it down.
“No, I feel like shit.” “In what form?”
“It’ll get better.” “Lately crack, but over the years, in every
“Yeah.” form that it exists.”
“‘Trust me.” She marks it down.
“Yeah.” “Anything else.”
The man leaves and he shuts the door and “Pills, acid, mushrooms, meth, PCP and glue.”
I’m alone. My feet bounce, I touch my face, I run Marks it down.
my tongue along my gums. I’m cold and getting “How often?”
colder. I hear someone scream. “When I have it.”
The door opens and a nurse walks into the “How often?”
room. She wears white, all white, and she is “A few times a week.”
­carrying a clipboard. She sits in the chair by the Marks it down.
desk. She moves forward and draws out a
“Hi James.” stethoscope.
“Hi.” “How are you feeling.”
“I need to ask you some questions.” “Terrible.”
“All right.” “In what way?”
“I also need to check your blood pressure and “In every way.”
your pulse.” She reaches for my shirt.
“All right.” “Do you mind?”
“What type of substances do you normally “No.”
use?” She lifts my shirt and she puts the stethoscope
“Alcohol.” to my chest. She listens.
“Every day?” “Breathe deeply.”
“Yes.” She listens.
“What time do you start drinking?” “Good. Do it again.”
“When I wake up.” She lowers my shirt and she pulls away and
She marks it down. she marks it down.
“How much per day?” “Thank you.”
“As much as I can.” I smile.
“How much is that?” “Are you cold?”
“Enough to make myself look like I do.” “Yes.”
She looks at me. She marks it down. She has a blood pressure gauge.
 Definitions of Addiction 17

BOX 1.3 (cont’d)

“Do you feel nauseous?” I stand. I look around me. I don’t know any-
“Yes.” thing. Where I am, why, what happened, how to
She straps it on my arm and it hurts. escape. My name, my life.
“When was the last time you used?” I curl up on the floor and I am crushed by
She pumps it up. images and sounds. Things I have never seen or
“A little while ago.” heard or even knew existed. They come from the
“What and how much?” ceiling, the door, the window, the desk, the chair,
“I drank a bottle of vodka.” the bed, the closet. They’re coming from the fuck-
“How does that compare to your normal daily ing closet. Dark shadows and bright lights and
dosage?” flashes of blue and yellow and red as deep as the
“It doesn’t.” red of my blood. They move toward me and they
She watches the gauge and the dials move and scream at me and I don’t know what they are but
she marks it down and she removes the gauge. I know they’re helping the bugs. They’re scream-
“I’m gonna leave for a little while, but I’ll be ing at me.
back.” I start shaking – shaking and shaking and shak-
I stare at the wall. ing. My entire body is shaking and my heart is rac-
“We need to monitor you carefully and we ing and I can see it pounding through my chest
will probably need to give you some detoxifica- and I’m sweating and it stings. The bugs crawl
tion drugs.” onto my skin, and they start biting me and I try to
I see a shadow and I think it moves but I’m kill them. I claw at my skin, tear at my hair, start
not sure. biting myself. I don’t have any teeth and I’m biting
“You’re fine right now, but I think you’ll start myself and there are shadows and bright lights
to feel some things.” and flashes and screams and bugs, bugs, bugs. I
I see another one. I hate it. am lost. I am completely fucking lost.
“If you need me, just call.” I scream.
I hate it. I piss on myself.
She stands up and she smiles and she puts the I shit my pants.
chair back and she leaves. I take off my shoes and The nurse returns and she calls for help and
I lie under the blankets and I close my eyes and men in white come in and they put me on the
I fall asleep. bed and they hold me there. I try to kill the bugs
I wake and I start to shiver and I curl up and but I can’t move so they live. In me. On me. I feel
I clench my fists. Sweat runs down my chest, the stethoscope and the gauge and they stick a
my arms, the backs of my legs. It stings my needle in my arm and they hold me down.
face. I am blinded by blackness.
I sit up and I hear someone moan. I see a bug I am gone.
in the corner, but I know it’s not there. The walls
close in and expand. They close in and expand Excerpt from A Million Little Pieces by James Frey, © 2003
by James Frey. Used by permission of Doubleday, an imprint of
and I can hear them. I cover my ears but it’s not the Knopf Doubleday Publishing Group, a division of Random
enough. House LLC. All Rights Reserved.
18 1. WHAT IS ADDICTION?

TABLE 1.3 12-Month Prevalence of Comorbid Disorders among Respondents with Nicotine Dependence, Alcohol
Dependence, or any Substance Use Disorder
Mood Anxiety Personality

Alcohol 27.6% 23.5% 39.5%

Nicotine 21.1% 22.0% 31.7%

Substance Dependence 29.2% 24.5% 69.5%

(including alcohol but not nicotine)

Data from:
Grant BF, Hasin DS, Chou SP, Stinson FS, Dawson DA, Nicotine dependence and psychiatric disorders in the United States: results from the National
Epidemiologic Survey on Alcohol and Related Conditions, Archives of General Psychiatry, 2004, (61), 1107–1115.
Grant BF, Stinson FS, Dawson DA, Chou SP, Dufour MC, Compton W, Pickering RP, Kaplan K, Prevalence and co-occurrence of substance use disorders
and independent mood and anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions, Archives of General
Psychiatry, 2004, (61), 807–816.
Grant BF, Stinson FS, Dawson DA, Chou SP, Ruan WJ, Pickering RP Co-occurrence of 12-month alcohol and drug use disorders and personality disorders
in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions, Archives of General Psychiatry, 2004, (61),
361–368.

the strongest associations are found with mood are 1.6 times more likely to become dependent
disorders, anxiety disorders, antisocial per- than people who begin to smoke when they are
sonality disorders, and conduct disorders. The older. Others have argued that regular smok-
association between attention-deficit/hyper- ing during adolescence raises the risk of adult
activity disorder (ADHD) and drug abuse can smoking by a factor of 16 compared with
be explained largely by the higher comorbid- nonsmoking during adolescence. The age at
­
ity with conduct disorder in these individuals. which smoking begins influences the total years
Independent of this association, little firm data of smoking, the number of cigarettes smoked,
indicate a higher risk caused by the pharma- and the likelihood of quitting (Figure 1.6). When
cological treatment of ADHD with stimulants, the prevalence of lifetime illicit or nonmedical
and no preference for stimulants over other drug use and dependence was estimated for
drugs of abuse has been noted. In fact, children each year of onset of drug use from ages ≤ 13
with ADHD who are treated with psychostim- and ≥ 21, the early onset of drug use was a sig-
ulants are less likely to develop a substance use nificant predictor of the subsequent develop-
disorder. ment of drug abuse (Figure 1.7). Overall, the
Developmental factors are important com- lifetime prevalence of substance dependence
ponents of vulnerability, with strong evidence (measured by the DSM-IV criteria) among
that adolescent exposure to alcohol, tobacco, ­people who began using drugs under the age
and drugs of abuse leads to a significantly of 14 was 34%. This percentage dropped to 14%
higher likelihood of drug dependence and for those who began using at age 21 or older.
drug-related problems in adulthood. Indi- The adolescent period is associated with spe-
viduals who experience their first intoxication cific stages and pathways of drug involvement.
at 16 or younger are more likely to drink and Initiation usually begins with legal drugs (alco-
drive, ride with an intoxicated driver, be seri- hol and tobacco). Involvement with illicit drugs
ously injured when drinking, become heavy occurs later in the developmental sequence, and
drinkers, and develop substance dependence marijuana is often the bridge between licit and
on alcohol (Figure 1.5). Similarly, people who illicit drugs. However, although this sequence
smoke their first cigarette at 14–16 years of age is common, it does not represent an inevitable
 Definitions of Addiction 19

FIGURE 1.6 Percentage of adolescent regular smokers

who became adult regular smokers as a function of grade
of smoking initiation. The subjects consisted of all consent-
ing 6th to 12th graders in a Midwestern county school system
in the United States who were present in school on the day
of testing. All 6th to 12th grade classrooms (excluding special
education) were surveyed annually between 1980 and 1983. A
potential pool of 5,799 individuals had been assessed at least
once during adolescence between 1980 and 1983. At the time
of follow-up, 25 of these subjects were deceased, 175 refused
participation, and 4,156 provided data (72%). The subjects
were predominantly Caucasian (96%), equally divided by sex
(49% male, 51% female), and an average of 21.8 years old. Of
the respondents, 71% had never been married, and 26% were
FIGURE 1.5 Representative college alcohol survey. currently married; 58% had completed at least some college
(A) Alcohol dependence according to age first intoxicated. (B) by the time of follow-up; 32% were still students; and 43% had
Past 30 days of heavy episodic drinking according to age first a high school education. For nonstudents, occupational status
intoxicated. After controlling for personal and demographic ranged from 29% in factory, crafts, and labor occupations, to
characteristics and respondent age, the odds of meeting alco- 39% in professional, technical, and managerial occupations.
hol dependence criteria were 3.1 times greater for those who At follow-up, the overall rate of smoking at least weekly was
were first drunk at or prior to age 12 compared with drink- 26.7%. [Taken with permission from Chassin L, Presson CC, Sher-
ers who were first drunk at age 19 or older. The relationship man SJ, Edwards DA. The natural history of cigarette smoking:
between early onset of being drunk and heavy episodic drink- predicting young-adult smoking outcomes from adolescent smoking
ing in college persisted even after further controlling for alco- patterns. Health Psychology, 1990, (9), 701–716.]
hol dependence. Respondents who were first drunk at or prior
to age 12 were 2.1 times to report recent heavy episodic drink-
ing than college drinkers who were first drunk at age 19 or Genetic contributions to addiction can result
older. [Taken with permission from Hingson R, Heeren T, Zakocs from complex genetic differences that range
R, Winter M, Wechsler H. Age of first intoxication, heavy drinking, from alleles that control drug metabolism to
driving after drinking and risk of unintentional injury among US hypothesized genetic control over drug sensi-
college students. Journal of Studies on Alcohol, 2003, (64), 23–31.]
tivity and environmental influences. The c­ lassic
approach to studying complex genetic traits is
progression. Only a very small percentage of to examine co-occurrence or comorbidity in
young people progress from one stage to the next monozygotic vs. dizygotic twins who are reared
and on to late-stage illicit drug use or dependence together or apart or in family studies with
(for further reading, see Kandel, 1975). ­biological relatives. Twin and adoption studies
20 1. WHAT IS ADDICTION?

TABLE 1.4 Heritability Estimates for Drug

Dependence
Males Females

Cocaine 44% 65%

Heroin (opiates) 43% –

Marijuana 33% 79%

Tobacco 53% 62%

Alcohol 49% (40–60%) 64%

Addiction overall 40%

Male cocaine, heroin, marijuana: Tsuang MT, Lyons MJ, Eisen SA,
FIGURE 1.7 Prevalence of lifetime drug dependence Goldberg J, True W, Lin N, Meyer JM, Toomey R, Faraone SV, Eaves L,
by age at first drug use. The prevalence of lifetime depen- Genetic influences on DSM-III-R drug abuse and dependence: a study of
dence decreased steeply with increasing age of onset of drug 3,372 twin pairs, American Journal of Medical Genetics, 1996, (67),
use. Overall, the prevalence of lifetime dependence among 473–477.
those who started using drugs under the age of 14 years was Male nicotine: Carmelli D, Swan GE, Robinette D, Fabsitz RR, Heritabil-
approximately 34%, dropping sharply to 15.1% for those ity of substance use in the NAS-NRC Twin Registry, Acta Geneticae
who initiated use at age 17, to approximately 14% among Medicae et Gemellologiae, 1990, (39), 91–98.
Female cocaine: Kendler KS, Prescott CA, Cocaine use, abuse and
those who initiated use at age 21 or older. [Taken with permis-
dependence in a population-based sample of female twins, British Journal
sion from Grant BF, Dawson DA. Age of onset of drug use and its
of Psychiatry, 1998, (173), 345–350.
association with DSM-IV drug abuse and dependence: results from Female marijuana: Kendler KS, Prescott CA, Cannabis use, abuse, and
the National Longitudinal Alcohol Epidemiologic Survey. Journal dependence in a population-based sample of female twins, American
of Substance Abuse, 1998, (10), 163–173.] Journal of Psychiatry, 1998, (155), 1016–1022.
Female nicotine: Kendler KS, Neale MC, Sullivan P, Corey LA, Gardner
CO, Prescott CA, A population-based twin study in women of smoking
provide researchers with estimates of the extent initiation and nicotine dependence, Psychological Medicine, 1999, (29),
299–308.
to which genetics influence a given phenotype, Male alcohol: Liu IC, Blacker DL, Xu R, Fitzmaurice G, Lyons MJ,
termed heritability. Genetic factors may account Tsuang MT, Genetic and environmental contributions to the development
for approximately 40% of the total variability of of alcohol dependence in male twins, Archives of General Psychiatry,
2004, (61), 897–903; Prescott CA, Kendler KS, Genetic and environmental
the phenotype (Table 1.4). In no case does herita- contributions to alcohol abuse and dependence in a population-based sam-
bility account for 100% of the variability, which ple of male twins, American Journal of Psychiatry, 1999, (156), 34–40;
argues strongly for gene–environment interac- McGue M, Pickens RW, Svikis DS, Sex and age effects on the inheritance
of alcohol problems: a twin study, Journal of Abnormal Psychology,
tions, including the specific stages of the addic- 1992, (101), 3–17.
tion cycle, developmental factors, and social Female alcohol: McGue M, Pickens RW, Svikis DS, Sex and age effects
factors. on the inheritance of alcohol problems: a twin study, Journal of Abnormal
Psychology, 1992, (101), 3–17.
Genetic factors can also convey protection Addiction overall: Uhl GR, Grow RW, The burden of complex genetics in
against drug abuse. For example, certain Asian brain disorders, Archives of General Psychiatry, 2004, (61), 223–229.
populations who lack one or more alleles for the
acetaldehyde dehydrogenase gene show signifi- NEUROADAPTATIONAL VIEWS
cantly less vulnerability to alcoholism. A simi- OF ADDICTION
lar genetic defect in metabolizing nicotine has
been discovered, in which those who metabo-
Behavioral Sensitization
lize nicotine more quickly have higher smoking
rates and may also have a higher vulnerability Repeated exposure to many drugs of abuse
to dependence (for further reading, see Tyndale results in progressive and enduring enhance-
et al., 2001). ment of the motor stimulant effect elicited by