1. The Science of Addiction: Implications for Policy Wilson M
The Science of Addiction: Implications for Policy Wilson M. Compton, MD, MPE Director, Division of Epidemiology, Services, and
Prevention Research
National Institute on Drug Abuse
USA

2. Addictions are common, developmental brain diseases expressed as compulsive behavior through continued use of a drug despite negative consequences: Onset depends on many intrinsic and extrinsic factors.
Biology
Genes/Development
Environment
DRUG/ALCOHOL
Brain Mechanisms
Addiction

3. Addictions are brain diseases
Human development is key
Treatment can be based on neuroscience advances
Policies need to account for the nature of addictive disorders

4. Addictions are brain diseases
Human development is key
Treatment can be based on neuroscience advances
Policies need to account for the nature of addictive disorders

5. ADDICTION IS A DISEASE OF THE BRAIN
as other diseases it affects the tissue function
Control Cocaine Abuser
Decreased Brain Metabolism in Drug Abuse
High
Low
Decreased Heart Metabolism in Heart Disease
Healthy Heart
Diseased Heart
Sources: From the laboratories of Drs. N. Volkow and H. Schelbert

6. Addictions are brain diseases
Human development is key
Treatment can be based on neuroscience advances
Policies need to account for the nature of addictive disorders

7. Addiction Is Developmental Age of Onset of Drug Abuse and Dependence
Addiction is also characterized as a developmental disorder characterized by increased risk for substance use disorder for tobacco MJ and alcohol
There are many factor that contribute to the increase in incidence including
-Social/ environmental factors
- Genetic and
Neurobiological factors (Sowell brain volume subtraction method between normal year old adolescents and year old young adults revealed parietal, temporal and occipital lobes showed little maturational change but, importantly, dorsal, medial and lateral regions of the frontal lobes (purple) those regions involved in executive function and inhibitory control were less developed.
Adolescents with risk haplotype on Chromosome 15 that start smoking before age 15 go on to become more dependent to tobacco as adults than those with other haplotypes
Universal Prevention intervention research is aimed at developing and testing programs that can reduce drug initiation and use during this vulnerable developmental period.
Age of Onset of Drug Abuse and Dependence
Source: Compton, et al. Archives of General Psychiatry NESARC Study.

8. Reinforcers (per session)
Effects of a Social Stressor on Brain Dopamine D2 Receptors and Propensity to Administer Drugs * S
.003
.01
.03 .1 10 20 30 40 50
Reinforcers (per session)
Cocaine (mg/kg/injection)
Dominant
Subordinate
Individually
Housed
Becomes Subordinate
Stress remains
Group
Housed
Becomes Dominant
No longer stressed
Social Setting Can Change Neurobiology
Morgan, D. et al. Nature Neuroscience, 2002.

9. Adverse Childhood Experiences (ACE) and Illicit Drug Use (n = 8603)2 4 6 8 10 1 3 5
Odds ratio
ACE Score
Ever Addicted
1.0
SR Dube, et al. PEDIATRICS 111: , 2003 9

10. Social Neglect During Early Childhood Decreases Brain Connectivity
r = , p=.01
Children with deprivation (n=17) vs controls (n=15) had decreased connectivity in uncinate fasciculus (connects amygdala with frontal cortex), proportional to time in orphanage. This could facilitate heightened emotional reactivity and impaired cognitive control.
Govindan et al., Cereb Cortex 2009

11. A gradient of childhood self-control predicts health, wealth, and public safety (Dunedin Study; children)
Health
Wealth
Criminal behavior
Children with low self-control had poorer health, more wealth problems, more single-parent child rearing, and more criminal convictions and drug use than those with high self-control
Moffitt et al., PNAS 2011
Since self-control can be improved by interventions early childhood intervention that enhances self-control is likely to bring a greater return on investment than harm reduction programs targeting adolescents alone.

12. Nurse Home Visiting during pregnancy and the first two years of life
Results from the 2008 National Survey on Drug Use and Health (NSDUH)
Substance Abuse and Mental Health Services Administration
Nurse Home Visiting during pregnancy and the first two years of life
has an impact on substance use, mental health and academic achievement at 12 years of age
Percent of Children Who Used Tobacco,
Alcohol, or Marijuana (Last 30 Days)
Child Age 12
Percent of Children with Internalizing Problems
(Borderline or Clinical)
Child Age 12
PIAT Scores - Reading & Math – Age 12 (Born to Low-Resource Mothers)
Percent of Mothers with Role Impairment
due to Alcohol or Drug Use – Child Age 12
Arch Pediatr Adoles Med, 164(5) , 2010

13. Addictions are brain diseases
Human development is key
Treatment can be based on neuroscience advances
Policies need to account for the nature of addictive disorders

14. Dopamine Movement Motivation Addiction Reward & well-being
It’s About Dopamine (mostly)
Dopamine is the brain’s primary “pleasure chemical”
Dopamine plays a role in attention, problem solving, and the anticipation of reward
Dopamine is implicated in the drug high, as well as in the craving that accompanies withdrawal.
Dopamine is a brain chemical involved in many different functions including movement, motivation, reward — and addiction. Nearly all drugs of abuse directly or indirectly increase dopamine in the pleasure and motivation pathways and in so doing, alter the normal communication between neurons.
Addiction
Reward & well-being

15. But Dopamine is only Part of the Story
Other neurotransmitter systems are also implicated
Serotonin
Regulates mood, sleep, etc.
Glutamate
Regulates learning and memory, etc.
And Others
Dopamine is an important brain chemical in drug abuse and addiction, but other brain systems and brain chemicals are also involved. Serotonin and glutamate neurotransmitter systems, for example, are among those affected. These neurotransmitters are important regulators of mood, sleep, learning and memory, and more.
These and other brain neurochemicals and electrical signals are responsible for your ability to think, move, feel, and behave.

16. Why Can’t Addicts Just Quit?
Key Question:
Why Can’t Addicts Just Quit?

17. Drug Abuse and Addiction
Circuits Involved In
Drug Abuse and Addiction
PFC
ACG
EXECUTIVE FUNCTION/
INHIBITORY
CONTROL
OFC
SCC
MOTIVATION/
DRIVE
Hipp
Amyg
MEMORY/
LEARNING
NAcc VP
REWARD

18. Drugs of Abuse Engage Systems in the Motivation Pathways of the Brain
NAcc VP
REWARD
Reward Circuit
Drugs of Abuse Engage
Systems in the
Motivation
Pathways
of the Brain

19. Natural Rewards Elevate DA Concentration (% Baseline)
Dopamine Levels
Food
Sex
200
200
NAc shell
150
150
Natural rewards stimulate dopamine neurotransmission. Eating something that you enjoy or being stimulated sexually can cause dopamine levels to increase. In these graphs, dopamine is being measured inside the brains of animals. Its increase is shown in response to food or sex cues. This basic mechanism of controlled dopamine release and reuptake has been carefully shaped and calibrated by evolution to reward normal activities critical for our survival.
DA Concentration (% Baseline)
% of Basal DA Output
100
100
Empty 50
Box Feeding
Female Present 1 2 3 4 5 6 7 8 60
120
180
Sample
Number
Time (min)
Di Chiara et al., Neuroscience, 1999.,Fiorino and Phillips, J. Neuroscience, 1997. 19

20. All Drugs Abused by Humans Raise Brain Dopamine Levels in the Nucleus Accumbens`
Time After Methamphetamine
Dopamine (nM)
METHAMPHETAMINE
2000
1500
1000
500 5 1
2.5
Dose (mg/kg IV)
min
250
NICOTINE
200
% of Basal Release
150
100 1 2
3 hr
Time After Nicotine
Nestler, Nature Neurosci, 2005
Di Chiara et al.

21. Increases in Dopamine are Associated with Perceived “High”
NAcc VP
REWARD T Y R O S I N E T Y R O S I N E D O P A D O P A D A D A DA D A DA D A D A
-10 10 20 30 40 -2 2 4 6 8
Self-Reports
(0-10)
Change in Dopamine
Bmax/kd (Placebo - MP)
“High” D A D A
raclopride D A D A D A m e t h y l p n i d a D A D A
raclopride D A R R D A D A D A R R R R
Volkow et al., JPET 291(1): , 1999. 21

22. “People, Places and Things…”
Hipp
Amyg
MEMORY/
LEARNING
2. Memory circuit
“People, Places and Things…”

23. Cocaine Craving:
Population (Cocaine Users, Controls) x Film (cocaine )
Cingulate
Ant Cing
Signal Intensity (AU)
Cocaine Film
IFG
Controls Cocaine Users
Garavan et al A .J. Psych 2000

24. 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

25. Volkow et al J Neuroscience 2006
Dopamine Release Increases when Viewing Cocaine Cues: [11C]Raclopride Binding In Cocaine Abusers (n=18) Viewing a Neutral and a Cocaine-Cue Video
Neutral video
Viewing a video of cocaine scenes decreased specific binding of [11C]raclopride presumably from DA increases
Volkow et al J Neuroscience 2006

26. ACG
OFC
SCC
INHIBITORY
CONTROL
EXECUTIVE
FUNCTION
PFC
MOTIVATION/
DRIVE
Motivation & Executive
Control Circuits
Dopamine is also associated with motivation and executive function via regulation of frontal activity.

27. Relationship Between Brain Glucose Metabolism
and Striatal D2 Receptors 30 40 50 60 70 80 90
2.9 3
3.1
3.2
3.3
3.4
3.5
3.6
D2 Receptors (BPND) 35 45 55 65
1.8 2
2.2
2.4
2.6
2.8
Control
Cocaine Abuser
control addicted
Brain glucose metabolism
Controls
Methamphetamine
Abusers
umol/100gr/min
OFC 4
Controls
Alcoholics
Volkow et al., PNAS (37):
DA D2 receptors

28. ADDICTION Becomes severely disrupted in
The fine balance in connections that normally exists
between brain areas active in reward, motivation,
learning and memory, and inhibitory control
EXECUTIVE
FUNCTION
PFC
ACG
INHIBITORY
CONTROL
Hipp
OFC
REWARD
SCC
NAcc VP
MOTIVATION/
DRIVE
Amyg
MEMORY/
LEARNING
Becomes severely disrupted in
ADDICTION

29. GO Non-Addicted Brain Addicted Brain STOP Memory Memory Stress
Drive
Memory
Saliency
Control
Drive
OFC
Saliency
NAc
Memory
Amygdala
Control CG
Drive
Memory
Saliency
STOP GO
Stress
Reactivity
Stress
Reactivity

30. Effective Strategies Attend to Multiple Aspects of Addiction:
Behavior
Biology
Social Context

31. Improving Prefrontal Function
A Double Blind, Placebo Controlled Trial Of NEPICASTAT (Dβh Inhibitor) In Cocaine Dependence[Biotie/NIDA]
Nepicastat attenuates cue-induced reinstatement of cocaine seeking
Nepicastat increases DA in PFC (but not in Nac)
Schroeder et al., Neuropsychopharmacology. 2013
Devoto et al., Addict Biol. 2013

32. Treatment Clinical Trials Network (CTN)
National Drug Abuse
Treatment Clinical Trials
Network (CTN)
NIDA Criminal Justice Drug Abuse Treatment Studies (CJ-DATS)
The CTN framework consists of thirteen Nodes linked with Community-based Treatment programs
The sites for these networks span the us and provide an extensive net opportunity to test the efficacy of novel treatment for addiction in both a public health and public safety environment
50-66% of inmates meeting standard diagnostic criteria for alcohol/drug dependence or abuse, according to the Bureau of Justice Statistics. Mumola CJ and Kerberg JC. Drug use and dependence, state and federal prisoners, Washington, DC: U.S. Department of Justice, Office of Justice Programs, Bureau of Justice Statistics, 2006.
The vast majority of criminal offenders who would benefit from treatment (80-85%) do not receive it, Mumola CJ and Kerberg JC. Drug use and dependence, state and federal prisoners, Washington, DC: U.S. Department of Justice, Office of Justice Programs, Bureau of Justice Statistics, 2006.
Karberg JC and James DJ. Substance dependence, abuse, and treatment of jail inmates, Washington, DC.: Office of Justice Programs, Bureau of Justice Statistics, 2005.
CTN Sites
Research Centers

33. Addictions are brain diseases
Human development is key
Treatment can be based on neuroscience advances
Policies need to account for the nature of addictive disorders

34. Brain and Behavioral Impact of Televised
Anti-Tobacco Public Service Announcements: Predictive Value
Left, dMPFC activation associated with AS by MSV interaction. Statistical map (yellow-red scale) is displayed over the MNI brain template and thresholded at z = 3.1 (cluster corrected at p < 0.001). Right, Correlation between percentage BOLD signal change in dMPFC and predicted cotinine levels at 1 month follow-up, adjusting for the baseline cotinine levels and AS groups.
Left, dMPFC activation associated with argument strength (AS) by “message sensation value” MSV interaction predicted cotinine levels one month after add presentation.
Wang A et al. J. Neurosci. 2013;33:

35. Addressing Drugs and Crime
Public Health Approach
- disease
- treatment
Public Safety Approach
- illegal behavior
- punish
High Attrition
High Recidivism

36. Successful Reentry Programs Use an Integrated Public Health-Public Safety Strategy
Close supervision
Community-based treatment
Blends functions of criminal justice and treatment systems to optimize outcomes
Consequences for noncompliance are certain and immediate
Opportunity to avoid incarceration or criminal record

37. Summary: Drug Addiction is a Brain Disease Involving Reward, Memory and Control Circuits
Addiction comes about by laying down and strengthening new memory connections in various circuits in the brain.
Long-lasting brain changes are responsible for the distortions of thought and emotionthat characterize addicts, including the compulsion to use drugs that is the essence of addiction.
Policies to prevent and treat addiction can benefit from an understanding of the science of addiction.