Addiction is a Brain Disease: Blending Research and Practice

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Addiction is a Brain Disease Blending Research
and Practice

• Lucinda L. Miner, Ph.D.
• Deputy Director, Office of Science Policy and
  Communications
• National Institute on Drug Abuse

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Advances in Science Have Revolutionized Our
Fundamental Views of Drug Abuse and Addiction
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Your Brain on Drugs
Front of brain
Back of brain
YELLOW shows places in brain where cocaine goes
(Striatum)
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There is a Unique DisconnectBetween the
Scientific Factsand the Public's Perception
AboutDrug Abuse and Addiction
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Drug Abuse Is A Preventable Behavior
Drug Addiction Is A Treatable Disease
Partnership for a Drug Free America
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Initial Drug Use Is A Voluntary Behavior A
Person Chooses to Take a Drug for the First Time
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Why Do People Take Drugs In The First Place?
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People Take Drugs To
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A Major Reason People Take a Drug is They Like
Whatit Does to Their Brains
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precursor
synthesis
storage
degradation
reuptake
release
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Natural Rewards Elevate Dopamine Levels
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Prolonged Drug Use Changes The Brain In
Fundamental and Long-Lasting Ways
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Striatal FDOPA Activity
Pre-Amphetamine/Control
Post-Chronic Amphetamine (10 days)
4 weeks
6 months
1 year
2 years
Superior Inferior
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Normal
Cocaine Abuser (10 Days)
Cocaine Abuser (100 Days)
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Dopamine Transporters in Methamphetamine Abusers
2.4
2.2
2.0
1.8
Normal Control
(Bmax/Kd)
Dopamine Transporters
1.6
1.4
1.2
1.0
Methamphetamine Abuser
p Methamphetamine abusers have significant
reductions in dopamine transporters.
BNL - UCLA - SUNY NIDA - ONDCP - DOE
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Dopamine Transporters in Methamphetamine Abusers
Motor Task
Loss of dopamine transporters in the meth
abusers may result in slowing of motor reactions.
Dopamine Transporter
Bmax/Kd
Time Gait
(seconds)
Memory Task
Loss of dopamine transporters in the meth
abusers may result in memory impairment.
Delayed Recall
(words remembered)
BNL/UCLA/SUNY
NIDA, ONDCP, DOE
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Implication Compromised dopamine systems
contribute to the consequences of drug
addiction.
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C-11d-threo-methylphenidate
Normal Control
DAT Recovery with prolonged abstinence
from methamphetamine
Methamphetamine Abuser (1 month detoxification)
Methamphetamine Abuser (24 month abstinent)
Source Volkow, N.D. et al., Journal of
Neuroscience, 21(23), pp. 9414-9418, December 1,
2001.
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Many Things Are Happening During the Transition
Between Voluntary Drug Use and Addiction
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What is the switch for addiction?

• What are the adaptive changes that occur in the
  brain that turn on addiction?

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Its Likely That the Transition Involves
Both Learning and Memory Events
Drug Use
Addiction
and Cellular Adaptations
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Research Has Shown that the Brain Circuitry
Involved in Addiction Has Similarities to that of
Other Motivational Systems
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Dopamine D2 Receptors in Addiction
Experimental groups
Control groups
Cocaine
DA D2 Receptor Availability
Meth
Alcohol
Food
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Implication Elucidation of the mechanism of
drug addiction will help to understand other
addictive behaviors
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Memories Appear to Be A Critical Part of
Addiction
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The Memory of Drugs
Amygdalanot lit up
Amygdalaactivated
Front of Brain
Back of Brain
Nature Video
Cocaine Video
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Drugs Usurp Brain Circuits
and Motivational Priorities
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Cocaine Craving Population (Cocaine Users,
Controls) x Film (cocaine, erotic)
Cingulate
Ant Cing
Signal Intensity (AU)
Cocaine Film
IFG
Controls Cocaine Users
Garavan et al A .J. Psych 2000
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Cocaine Craving Population (Cocaine Users,
Controls) x Film (cocaine, erotic)
Cingulate
Ant Cing
Signal Intensity (AU)
IFG
Controls Cocaine Users
Garavan et al A .J. Psych 2000
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This Results in Motivational Toxicity and
Compulsive Drug Use (Addiction)
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Addiction is a Brain Disease Expressed As
Compulsive Behavior Both Developing and
Recovering From It Depend on Behavior and
Social Context
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Social Dominance in Monkeys Dopamine Receptors
and Cocaine Self-AdministrationDopamine Receptor
Density
Morgan et al, Nature Neuroscience 2002
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Effect of Social Dominance on CocaineSelf
-Administration
TOTAL INTAKE (mg/kg/session)
2.0

1.5
Mean intake/session (mg/kg)
1.0

0.5
Subordinate Dominant
0.0
.003
.01
.03
.1
Cocaine (mg/kg/injection)
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Drug Addiction A Complex Behavioral and
Neurobiological Disorder
PHYSIOLOGICAL
HISTORICAL
DRUGS
- genetics- circadian rhythms- disease states-
gender
- previous history- expectation- learning
ENVIRONMENTAL
- social interactions- stress- conditioned
stimuli
BRAIN MECHANISMS
BEHAVIOR
ENVIRONMENT
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Addiction is the Quintessential Biobehavioral
Disorder
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Thats Why Addicts Cant Just Quit
Thats Why Treatment Is Essential!
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Treating A Brain DiseaseMust Go Beyond
JustFixing The Chemistry
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Challenge
Drug Use
Addiction
Treatment
Normal
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A Major Task for Drug Treatment is Changing
Brains Back!
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We Need to Treat the Whole Person!
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The Most Effective Treatment Strategies Will
Attend to All Aspects of Addiction

• Biology
• Behavior
• Social Context

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In Treating Addiction
We Need to Keep Our Eye on the Real Target
Abstinence
Functionality in Family, Work and Community
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Drug Abuse Treatment Core Components and
Comprehensive Services
Medical
Mental Health
Financial
Vocational
Housing Transportation
Educational
Child Care
Legal
Family
AIDS / HIV Risks
Etheridge, Hubbard, Anderson, Craddock, Flynn,
1997 (PAB)
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We Are Using Science to Develop Even Better
Treatment
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Methamphetamine
Opiates
Cocaine
Cabergoline Disulfiram (Antabuse)
Reserpine Selegiline
Bupropion
Lofexidine
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NIDA-Funded Behavioral Therapy Research

• Stage I
• Reducing HIV Risk Behaviors in IV Drug Users
• Treatment for Substance Abuse in Schizophrenia
• Prescriptive Therapy for Drug Abuse with
  Depression
• Concurrent Treatment of PTSD and Cocaine
  Dependence
• Therapy Development for Smoking Cessation
• Duration and Pacing Effects on Smoking Reduction
• Enhancing Readiness to Change is Schizophrenics 
• Career/Training in Drug Abuse Research
• Dual Diagnosis Adherence Strategies
• Adapting Behavioral Marital Therapy to Treat Drug
  Abuse
• The Therapy Relationship and Anxiolytic
  Dependence
• Adherence Therapy for Opioid Abusing Pain
  Patients 
• Treatment of Nicotine Dependent Smokers
• Smoking Cessation Intervention for Youth
• Expectancy-based Coping Skills Therapy
• Treating Nicotine Addiction in Pregnancy
• Treating the Partners of Drug Using Pregnant
  Women   
• Behavioral Therapy For Depression In Drug
  Dependence

Stage III Psychotherapy Development for Cocaine
and Opioid Abuse Transporting Family Therapy to
Adolescent Day Treatment Moving Motivational
Interviewing Into Practice Contingency Management
for Real-Life Drug Treatment Evaluating
Manual-guided Training in Clinical
Settings Training Clinicians to Perform Validated
Therapies TSF  

• Stage II
• Smoking Cessation For Pregnant Substance-Dependent
  Woman
• Treatment of Drug Dependence and Psychiatric
  Illness
• Psychotherapy of Substance Use Disorders
• Treating Chinese Smokers with Interactive Expert
  Systems
• Improving Efficacy of Drug Abuse Treatment
• Psychotherapy Development for Cocaine and Opioid
  Abuse
• Treatments for Complex Patients in New Settings
• Motivating Marijuana Cessation
• Opiate Dependence Combined Naltrexone/Behavior
  Therapy
• Promoting Entry to Treatment A Service
  Enhancement
• Behavioral Therapy for Gay Male Methamphetamine
  Abusers
• Reducing High Risk Behavior in HIV-Positive Drug
  Abusers
• Aftercare for Cocaine Patients Effectiveness and
  Costs
• Motivational Interviewing for Teen Smokers in the
  ER
• Brief Intervention for Drug Use in Pregnant Women
• Relational Parenting Therapy for Opioid Abusing
  Mothers
• Expectancy-based Coping Skills Therapy
• Cocaine Dependence Medication and Behavioral
  Treatments

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So how come no ones using much of this stuff?
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Advances in Science Have Given Us A Broad Range
of Promising Options For Treating Addiction
BUT
We Must Work to Ensure That They Are Actually
Used in Practice
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If a Tree Falls in the Forest, and No One Is
Around

• Does It Really Make a Sound?

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If Research is Done and Only Published in Peer
Reviewed Journals
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that Remain on the Shelves.
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Does It Have An Impact on the Lives of
Individuals?
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Obstacles to Applying Research

• Plastic wrap on manuals often too tight to open.
• Off the shelf interventions often not readily
  accepted.
• May not work in real-life settings w/o
  modifications.
• Research often does not look at practical
  questions that determine effectiveness (e.g.,
  ease of training, attitudes, cost).

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although carefully controlled efficacy studies
of new treatment components are necessary to show
that the component can work, they are not
sufficient to show that the component will work
under broader, less controlled, and more
complicated real-world conditions.-McLellan,
JSAT, 22(4), 2002
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NIDA
What Are We Doing About All of This?
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National Drug Abuse Treatment Clinical Trials
Network
Seattle
Portland
New York City
Detroit
Boston
New Haven
Denver
Long Island
Philadelphia
Cincinnati
San Francisco (CA/AZ Node)
Baltimore/Richmond
Raleigh/ Durham
Albuquerque
Los Angeles
Charleston
Miami
CTN Sites
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CTN Current Protocols

• Buprenorphine/Naloxone Detoxification
• In-Patient/Out-Patient
• Motivational Enhancement Therapy
  (MET)/Motivational Interviewing (MI)
• Motivational Incentive Therapy
• Drug-Free Clinic/Methadone Clinic

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Protocols Ready to Enroll

• Baseline Study
• Bup/Nx Tapering Doses
• Smoking Cessation Treatment in Substance
  Rehabilitation Programs
• Bup/Nx for Adolescents
• Telephone Enhancement of Long-term Engagement
  (TELE)
• Infections and Substance Abuse

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Protocols Under Development

• HIV/STD prevention skills for men/women
• Treating women with trauma and SUDs
• Brief Strategic Family Therapy for adolescents
• Job seekers training
• MET for pregnant women
• Performance monitoring and feedback to counselors
• HIV intervention in drug treatment settings

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Enhancing Linkages to Ensure Research is Used
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Improving Application of CTN Findings via Linkage
with ATTCs
Seattle
Portland
New York City
Detroit
Boston
New Haven
Denver
Long Island
Philadelphia
Cincinnati
San Francisco (CA/AZ Node)
Baltimore/Richmond
Raleigh/ Durham
Albuquerque
Los Angeles
Charleston
Miami
Puerto Rico ATTC
CTN Sites
ATTC
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Our Strategy Involves BLENDING
Bringing Science-Based Technologies Into Ongoing
Community Practice
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Science Can Replace Ideology As the Foundation
For Drug Abuse and Addiction Prevention,
Treatment and Policy Strategies
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For More Information
NIDA Public Information Office 301-443-1124 Or
www.nida.nih.gov www.drugabuse.gov National
Clearinghouse on Alcohol and Drug Information
(NCADI) 1-800-729-6686
www.drugabuse.gov