The Science of Addiction From Neurobiology to Treatment

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The Science of Addiction
From Neurobiology to Treatment

Carlton K. Erickson, Ph.D

W. W. Norton & Company

New York • London
Copyright © 2007 by Carlton K. Erickson

All rights reserved

Printed in the United States of America
First Edition

For information about permission to reproduce selections from this book, write to
Permissions, W. W. Norton & Company, Inc., 500 Fifth Avenue, New York, NY 10110

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Library of Congress Cataloging-in-Publication Data

Erickson, Carlton K.
The science of addiction: from neurobiology to treatment / Carlton K. Erickson.
p. cm.
“A Norton professional book.”
Includes bibliographical references and index.
ISBN-13: 978-0-393-70463-1
ISBN-10: 0-393-70463-7
1. Substance abuse—Physiological aspects. 2. Substance abuse—Treatment. I. Title.

RC564.E7544 2006
616.86—dc22 2006047156

W. W. Norton & Company, Inc., 500 Fifth Avenue, New York, N.Y. 10110
www.wwnorton.com

W. W. Norton & Company Ltd., Castle House, 75/76 Wells St., London WIT 3QT

1 3 5 7 9 0 8 6 4 2
 Dedication
Anyone with a successful family knows that hard work, frequent travel,
and periods of serenity happen only because of the sacrifices of a loving
spouse and children. To my most supportive and beautiful wife, Eunice,
and the children, their spouses, and our grandchildren: Steig (Sheri and
Emma); Dirk (Jennifer); Annika Bennett (Bill, Hunter and Luke); and
Hans (Mandy and Hayden)—this book is dedicated to you.
 Contents
Abbreviations ix
Preface xi
Acknowledgments xv
Chapter 1. Terminology and Characterization of “Addiction” 1
Chapter 2. Basics of Brain Science 32
Chapter 3. Anatomy and Neurobiology of Chemical Dependence 50
Chapter 4. The Genetics of Chemical Dependence 74
Chapter 5. Stimulants and Depressants 92
Chapter 6. Alcohol 113
Chapter 7. Other Drugs 132
Chapter 8. Dependence Disease Treatment 150
Chapter 9. The Power and Limitations of Addiction Research 183
Chapter 10. Evidence-Based Research for the Future 199
Appendix A: Alcohol Concepts Affecting Neurobiology 215
and Treatment
Appendix B: Drug Concepts Affecting Neurobiology 227
and Treatment
Glossary 241
References 253
Index 277

vii
 Abbreviations

A.A. – Alcoholics Anonymous

ADH – Alcohol dehydrogenase
ADHD – Attention deficit hyperactivity disorder
ALDH – Aldehyde dehydrogenase
BAC – Blood alcohol concentration
BU – Beverage unit
CB – Cannabinoid receptor
CBT – Cognitive behavioral therapy
CNS – Central nervous system
COGA – Collaborative Study on the Genetics of Alcoholism
CRF – Corticotropin releasing factor
CT – Computerized tomography
DA - Dopamine
DAT – Dopamine transporter
DNA – Deoxyribonucleic acid
DRD2 – Dopamine receptor (type) D2
DSM-IV – Diagnostic and Statistical Manual of Mental Disorders,
Fourth Edition
DTs – Delirium tremens
DUDs – Drug-use disorders
DUI – Driving under the influence
DWI – Driving while intoxicated
ERP – Event-related potential
FAE – Fetal alcohol effects
FAS – Fetal alcohol syndrome
FASD – Fetal alcohol spectrum disorder
GABA – Gamma aminobutyric acid
GHB – Gamma hydroxybutyrate
GLU – Glutamate

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 The Science of Addiction

5-HT – Serotonin
ICD-10 – International Classification of Diseases, Tenth Revision
LSD – Lysergic acid diethylamide
MAO – Monamine oxidase
MDMA – Methylenedioxy methamphetamine
MDS – Mesolimbic dopamine system
MET – Motivational enhancement therapy
MI – Motivational interviewing
M.M. – Moderation management
MRI – Magnetic resonance imaging (fMRI = functional MRI)
mRNA – Messenger ribonucleic acid
N.A. – Narcotics Anonymous
NAcc – Nucleus accumbens
NIAAA – National Institute on Alcohol Abuse and Alcoholism
NIDA – National Institute on Drug Abuse
NMDA – N-methyl-D-aspartate
OCD – Obsessive compulsive disorder
OPD – Other psychiatric disorders
PCM – Primary-care management
PET – positron emission tomography
PNS – Peripheral nervous system
PTSD – Posttraumatic stress disorder
QTL – Quantitative trait locus
RAS – Reticular activating system
RM – Recovery management
rRNA – Ribosomal ribonucleic acid
RVE – Research validity estimate
SERT – Serotonin transporter
SIDS – Sudden infant death syndrome
SPECT – Single photon emission computerized tomography
SSRIs – Selective serotonin reuptake inhibitors
TBW – Total body water
TC – Therapeutic community
tRNA – Transfer ribonucleic acid
THC – Tetrahydrocannabinol
THIQs (TIQs) – Tetrahydroisoquinolines
TSF – Twelve-step facilitation
VTA – Ventral tegmental area

x
 Preface

THE MOST EXCITING NEWS about the “science of addiction” is that neuro-
science is playing a ground-breaking role in helping us clarify the exact
causes of compulsive alcohol and other drug use. Neuroscience research
on “addiction” involves an understanding of how drugs act on individ-
ual nerve cells as well as on large groups of nerve cells in the central
nervous system. Research is also helping us clarify what “addiction” is,
what it is not, and how it can be better treated. Unlike earlier alcoholism
and addiction research, neurobiological research on addicting drugs is
unique in that it interacts with so many other important areas: social
work, psychology, sociology, medicine, pharmacology, physiology,
genetics, brain imaging, epidemiology, and treatment research. Thus,
this book covers, in order: (1) changes in the terminology and conceptu-
alization of “addiction” that are emerging based on new neuroscience,
genetic, and clinical findings, and that help us understand why one type
of drug problem is a chronic medical brain disease; (2) the basics of neu-
roscience; (3) the neuroanatomy and function of brain reward sites; (4)
the genetics of alcohol and other drug dependence; (5) the basic pharma-
cology of stimulants and depressants; (6) the basic pharmacology of
alcohol; (7) the basic pharmacology of other drugs; (8) current and
emerging treatments for chemical dependence and how neuroscience
helps us understand the way they work; (9) how to evaluate the validity
of science in this area and how to read and interpret new research find-
ings; and (10) future research trends and important questions that addic-

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 The Science of Addiction

tion science should answer. The book closes with two appendices that
provide supplemental information on alcohol (Appendix A) and other
drugs (Appendix B).
The scientific conclusions that appear in this book are mine, and the
story they tell is the result of over 30 years of addiction science research.
Much of this research has substantiated the anecdotal reports told by
those in recovery from the disease. When science agrees with real-life
experience, and vice versa, the story is strengthened. Certainly, the story
will change subtlety as the scientific evidence grows, and other scientists
may draw somewhat different conclusions from those presented in this
book. Some may suggest that I have misinterpreted the results of some
scientific studies; others may say that I have missed key recent publica-
tions. Any omission of important research is unintentional: My goal is
to accurately and articulately represent a cross-section of the scientific
areas discussed in the text. The fact is that we have not yet solved the
causes of drug problems, nor do we have all the answers to cure people.
Thus, scientific conclusions are always open to challenge. The biggest
challenge is for all of us to educate policy makers and to advocate for
more alcohol and other drug research funding to find the final answers.
No person’s conclusions about the causes and best treatments for
“addictions” are stronger than the weight of their scientific data, and
more scientific data are urgently needed in this area!

Who This Book Can Help

Abuse of alcohol and illicit drugs affects millions of people on a daily
basis (Hanson & Li, 2003). Over 8 million U.S. individuals meet the
diagnostic criteria for alcohol dependence and another 5.6 million meet
the criteria for alcohol abuse (Grant, Hasin, Chou, Stinson, & Dawson,
2004). In 2001, there were about 66.5 million tobacco smokers and 16
million illicit drug users (Grant et al., 2004). The U.S. economic cost of
such abuse was estimated to be more than $484 billion per year, includ-
ing $185 billion due to alcohol overuse, $138 billion due to smoking,
and about $161 billion due to illicit drugs. Finally, of the more than 2
million U.S. deaths per year, around 1 in 4 is due to alcohol, tobacco, or
illicit drug use.

xii
 Preface

This book attempts to help the almost 21.6 million Americans and
millions more worldwide who abuse or are dependent on drugs (Volkow
& Li, 2005b), by teaching their caregivers (or them) about the latest
“addiction science” research. Through better definitions for drug-relat-
ed health conditions and a better understanding of drug action on the
brain and of how treatment works, the consequences of drug use will
decline. This book is about helping addiction professionals understand
the foundations and applications of neuroscience so that they will be
better able to empathize with their patients and apply such science to
principles of treatment. Experience and a few studies (see Lawson,
Wilcox, Littlefield, Pituch, & Erickson, 2004) have shown that when
professionals learn the proper scientific and clinical terminology, they
tend to incorporate it into their everyday language and professional care
environment. Thus, the value of this book is great to those who read it
with a goal of learning something new.

Note from the author: Although I work at the College of Pharmacy at

the University of Texas at Austin and hold an endowed professorship
originally funded by a pharmaceutical company, I have no vested inter-
est in pharmaceutical products and do not receive compensation from
the pharmaceutical industry or any other industries associated with alco-
hol or other drug products.

xiii
 Acknowledgments

MANY PEOPLE HAVE SUGGESTED, usually after an extremely long and tiring
6-hour workshop, that I write a book about the neuroscience of addic-
tion. But nothing can be more motivating than an invitation by a pub-
lisher. I am thus extremely grateful to Deborah Malmud, Michael
McGandy, and the staff at W. W. Norton for inviting me to submit a
book proposal, as well as for their expert editing during the writing
process. Deborah was extremely helpful and responsive to frequent
emails, especially during the early writing of the manuscript. Michael
has been a guiding light and provided most of the editing suggestions
during the latter stages of manuscript preparation. Our copy editor,
Casey Ruble, provided detailed editing with her extra hard work and
insight. A third editor at Norton, Kristen Holt-Browning, skillfully
pulled the entire manuscript together at the end.
Perhaps the unique nature of this book will show through in that I
not only know some science, but also quite a bit about alcoholism and
other drug addiction, treatment, and recovery. One doesn’t have to have
cancer to be a cancer researcher, and my interest in this topic is purely
academic. However, it is hard to be involved in addiction science with-
out becoming emotionally connected to those who are suffering. For
helping me understand the disease and putting it in context with the lat-
est science, I am forever grateful to John T. O’Neill, a friend with whom
I’ve discussed this topic almost daily for over 25 years. His teaching,
mentoring, intelligence, humor, and inspiration have made me the edu-
cator I am today. To other friends in the 12-step programs who have

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 The Science of Addiction

shared openly and often, especially Hank M. and Mike R., I am truly
blessed. I also thank John Schwarzlose, president of the Betty Ford
Center, who invited me to participate in a Professionals in Residence
program at that internationally known treatment center, and who con-
tinues to support the science of addiction through the center’s monthly
newsletter, Findings, for which I have the privilege of serving as science
editor. I am perhaps most indebted to the many people in recovery I have
met over the years for their open sharing, challenging questions, and
willingness to tell me when the science didn’t seem to connect with their
experience. When lecturing, whether to students or to treatment profes-
sionals, I always learn from the probing questions. I believe that more
scientific hypotheses can be generated by insightful questions or com-
ments from learners who look at things differently than I do. From my
students in recovery, I have learned about many issues that still need
much more research. Finally, I need to state that in my experience scien-
tists who design experiments while looking only at published literature
are narrowly focused indeed. Scientists who put their studies into con-
text with real-life people and outcomes have a greater insight into the
real truth. This is something I have tried to emulate.
I’ve noticed that there is a lot of finger-pointing when people are con-
cerned that the latest science on addiction is not getting into the hands
of the people who need it. The scientists blame the treatment profession-
als for not taking the time to read the latest scientific literature or to
attend educational science lectures. The treatment professionals tell the
scientists that they are boring and use confusing jargon, and the govern-
ment tries to get the two sides together. I feel fortunate that, like some of
my colleagues, I have the interest, love to take the time, and apparently
have the ability to be one of the scientific spokespeople who feel com-
fortable helping counselors, treatment and other health professionals,
attorneys, and administrators become excited about addiction science
and medicine. To the folks at the National Institute on Drug Abuse and
the National Institute on Alcohol Abuse and Alcoholism, I am thankful
for early contracts and grants that helped me become a critical scientist
and later to become interested in transforming myself into an addiction
science educator. This early funding helped our team at the Addiction
Science Research and Education Center in the College of Pharmacy at
the University of Texas at Austin develop an ongoing collaboration

xvi
 Acknowledgments

focusing on basic pharmacology and neuroscience, on how people learn,

how best to change their beliefs, and how to change their professional
behavior to better help their patients. Thanks to our interdisciplinary
research team: Rich Wilcox, Ken Lawson, John Littlefield, Keenan
Pituch, Joe Miller, and Mary Velasquez. Special appreciation to my col-
league Rich Wilcox, whose energy has produced several collaborative
manuscripts, and the dean, Steve Leslie, who is himself a prominent alco-
hol researcher. Most importantly, Dean Leslie has supported my search
for international understanding about these devastating diseases and has
tolerated and even encouraged my frequent travels. My colleague John
Brick, with whom I’ve written other books, is a much-appreciated friend
who continues to confirm and encourage my work. My friend Stephanie
Jones, who provided some of the reference materials, is to be commend-
ed for her enthusiasm in helping with the manuscript. Finally, I am most
indebted to my colleague Peter Pociluyko. Peter is that rare individual
who wanted to help by reading every word of the manuscript (at least
twice), making insightful comments and changes, and confirming why
certain material is important to the professionals in the field. I have
never met such a giving, trusting, caring, supportive, and faithful col-
league. Any success that this book might have is in large part due to his
help. To him, I am humbly indebted.
There are a number of people who helped review the raw material for
the appendices at the end of the book. They are all members of the fed-
erally funded Addiction Technology Transfer Centers (ATTCs): Mary
Beth Johnson, director of the national office of the ATTCs ( in Kansas
City, Missouri); Pat Stilen and Jan Wrolstad (Mid-America ATTC);
Wendy Hausotter (Northwest Frontier ATTC), Richard Spence and Phil
Orrick (Gulf Coast ATTC); and Michael Flaherty, Holly Hagle, Heidi
Norman, Melva Hogan, Joyce Boisell, Chris Hagle, and Iburia Scott-
Johnson (Institute for Research, Education and Training in the
Addictions, IRETA, and the Northeast ATTC).
Technically, I couldn’t have pulled this book together if it weren’t for
three employees in the College of Pharmacy at the university. Debbie
Brand, administrative associate in the Division of Pharmacology/
Toxicology, compiled the bibliography in her usual meticulous way. A
student, Heidi Lau, cheerfully checked the accuracy and completeness of
the references. Belinda Lehmkuhle in our Learning Resources Center

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 The Science of Addiction

drew and adapted most of the figures and tables, and her artistry also
lives on in the website of our Center.
Let us continue to keep in our prayers those who have suffered and
lost their lives to alcoholism and other drug addiction. Perhaps the infor-
mation in this book can prevent countless others from suffering the same
fate.

Permissions
The following publishers and individuals have kindly provided copy-
right permission for the indicated figures and tables. Tables and figures
not listed are original artwork or materials developed by the author
and individuals mentioned in the acknowledgments.
Table 1.3 – Adapted with permission from the Diagnostic and
Statistical Manual of Mental Disorders, Fourth Edition, Text Revision
Copyright 2000. American Psychiatric Association.
Figures 2.3, 3.2 – Adapted with permission from Cami, J. & Farre,
M. (2003). New England Journal of Medicine, 349, 975–986.
Copyright 2003. Massachusetts Medical Society. All rights reserved.
Figure 3.3 – Reprinted with permission from Koob, G. F. (2003).
Alcoholism: Clinical & Experimental Research, 27, 232–243.
Copyright 2003. Lippincott, Williams & Wilkins.
Figure 3.4 – Reprinted with permission from Koob, G.F. & LeMoal,
M. (1997). Science 278, 52–58. Copyright 1997. American Association
for the Advancement of Science.
Figure 3.5 – Adapted with permission from Kalivas, P.W. &
Volkow, N.D. (2005). American Journal of Psychiatry, 162,
1403–1413. Copyright 2005. American Psychiatric Association.
Figures 4.1, 4.2 – Adapted from Dick, D.M. & Faroud, T. (2002).
Alcohol Research & Health, 26, 172–174.
Table 4.1 – Adapted with permission from Mayer, P. and Hollt, V.
(2005). Current Opinion in Pharmacology, 5, 4–8. Copyright 2005.
Elsevier.
Figures 10.1, 10.2 – Courtesy of A. Pfefferbaum, Stanford
University.

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