implications for policy the science of addiction: implications for policy wilson m. compton, md, mpe...
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The Science of Addiction:Implications for Policy
Wilson M. Compton, MD, MPEDirector, Division of Epidemiology, Services, and
Prevention ResearchNational Institute on Drug Abuse
USA
AddictionAddiction
DRUG/ALCOHOLDRUG/ALCOHOL
Brain MechanismsBrain Mechanisms
BiologyGenes/Development
BiologyGenes/Development
EnvironmentEnvironment
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.
• 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
• 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
Healthy Heart
Diseased Heart
Decreased Heart Metabolism in Heart Disease
ADDICTION IS A DISEASE OF THE BRAINas other diseases it affects the tissue function
Control Cocaine Abuser
Decreased Brain Metabolism in Drug Abuse
Sources: From the laboratories of Drs. N. Volkow and H. Schelbert
High
Low
• 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
Addiction Is Development
al
5 10
15
20
25
30
35
40
45
50
55
60
0.000
0.002
0.004
0.006
0.008
0.010
0.012
DSM-IV Abuse
DSM-IV Dependence
Age
Haz
ard
Rat
e
Age of Onset of Drug Abuse and Dependence Source: Compton, et al. Archives of General Psychiatry 2007. NESARC Study.
8
IndividuallyHoused
Morgan, D. et al. Nature Neuroscience, 2002.
**
S.003.01 .03 .1
0
10
20
30
40
50
Rein
forc
ers
(p
er
sessio
n)
Cocaine (mg/kg/injection)
DominantSubordinate
Becomes SubordinateStress remains
GroupHoused
Becomes DominantNo longer stressed
Social Setting Can Change NeurobiologySocial Setting Can Change Neurobiology
Effects of a Social Stressor on Brain Dopamine D2 Receptors and
Propensity to Administer Drugs
Effects of a Social Stressor on Brain Dopamine D2 Receptors and
Propensity to Administer Drugs
0
2
4
6
8
10
0 1 2 3 4 5
Od
ds r
ati
o
ACE Score
Ever Addicted
Adverse Childhood Experiences
(ACE) and Illicit Drug Use (n = 8603)
SR Dube, et al. PEDIATRICS 111: 564-572, 2003
1.0
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.
Social Neglect During Early Childhood Decreases Brain Connectivity
Govindan et al., Cereb Cortex 2009
r = -0.604, p=.01
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
A gradient of childhood self-control predicts health, wealth, and public safety (Dunedin Study;
1000+ children)Health Wealth Criminal behavior
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.
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
Arch Pediatr Adoles Med, 164(5) 412-418, 2010
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
0
1
2
3
4
5
6
Nurse Comparison
0
1
2
3
4
5
6
Nurse Comparison
PIAT Scores - Reading & Math – Age 12(Born to Low-Resource Mothers)
80
85
90
Nurse Comparison
Percent of Mothers with Role Impairment due to Alcohol or Drug Use – Child Age 12
0
1
2
3
Nurse Comparison
• 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
Addiction Reward & well-being
Motivation
Movement
Dopamine
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
These and other brain neurochemicals and electrical signals are responsible for your ability to think, move, feel, and behave.
Key Question:
OFCOFCSCCSCC
MOTIVATION/DRIVE
MOTIVATION/DRIVE
HippHipp
Amyg
Amyg MEMORY/
LEARNING MEMORY/
LEARNING
Circuits Involved In Drug Abuse and Addiction
Circuits Involved In Drug Abuse and Addiction
NAcc
NAcc VPVP
REWARDREWARD
PFCPFC
ACGACG
EXECUTIVEFUNCTION/ INHIBITORY
CONTROL
EXECUTIVEFUNCTION/ INHIBITORY
CONTROL
NAcc
NAcc VPVP
REWARD
1. Reward Circuit
Drugs of Abuse EngageSystems in the Motivation Pathwaysof the Brain
Di Chiara et al., Neuroscience, 1999.,Fiorino and Phillips, J. Neuroscience, 1997.
Natural Rewards Elevate Dopamine Levels
0
50
100
150
200
0 60 120 180
Time (min)
% o
f B
asal D
A O
utp
ut NAc shell
Empty
Food Sex
Box Feeding
100
150
200
DA
Con
cen
trati
on
(%
Baselin
e)
SampleNumber
1 2 3 4 5 6 7 8
Female Present
All Drugs Abused by Humans Raise Brain Dopamine Levels in the Nucleus Accumbens
Nestler, Nature Neurosci, 2005
`̀
Time After Methamphetamine
Dop
am
ine (
nM
)
METHAMPHETAMINE2000
1500
1000
500
0
55
112.52.5
Dose (mg/kg IV)
0 20 40 60 80min
0
100
150
200
250
0 1 2 3 hrTime After Nicotine
% o
f B
asal R
ele
ase NICOTINE
Di Chiara et al.
TYROSINE
DA
DOPA
DA
DA
DA
DA
TYROSINE
DA
DOPA
DA
DA
DA
DADA DA DA
DADADA
methyl pheni date
RRRRRR
-10 0 10 20 30 40-202468
10
Self-
Rep
ort
s(0
-10
)Change in Dopamine
Bmax/kd (Placebo - MP)
“High”
Increases in Dopamine are Associated with Perceived “High”
racloprideraclopride
DA DA
Volkow et al., JPET 291(1):409-415, 1999.
NAccNAcc VPVP
REWARDREWARD
HippHipp
Amyg
AmygMEMORY/LEARNING
2. Memory circuit
“People, Places and Things…”
Cocaine Film
Cocaine Craving:Population (Cocaine Users, Controls) x Film (cocaine )
Garavan et al A .J. Psych 2000
IFG
Ant Cing
Cingulate
Sig
nal In
ten
sit
y (
AU
)
Controls Cocaine Users
Cocaine Film Erotic Film
Cocaine Craving:Population (Cocaine Users, Controls) x Film (cocaine, erotic)
Garavan et al A .J. Psych 2000
IFG
Ant Cing
Cingulate
Sig
nal In
ten
sit
y (
AU
)
Controls Cocaine Users
Dopamine Release Increases when Viewing Cocaine Cues: [11C]Raclopride
Binding In Cocaine Abusers (n=18) Viewing a Neutral and a Cocaine-Cue Video
Viewing a video of cocaine scenes decreased specific binding of
[11C]raclopride presumably from DA increases
Neutral video
Volkow et al J Neuroscience 2006
3. Motivation & Executive Control Circuits
ACGACG
OFCOFCSCCSCC
INHIBITORY CONTROL
INHIBITORY CONTROL
EXECUTIVEFUNCTIONEXECUTIVEFUNCTION
PFCPFC
MOTIVATION/DRIVE
MOTIVATION/DRIVE
Dopamine is also associated with motivation and executive function via regulation of frontal activity.
ControlsMethamphetamineAbusers
OFC
um
ol/1
00g
r/m
in
4
0
Controls
Alcoholics
con
trol
ad
dic
ted
Bra
in g
lucose m
eta
bolism
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)
1.5 2 2.5 3 3.5 425
30
35
40
45
50
D2R VS(Bmax/Kd)
Meta
bolis
m CG
(micr
omol/
100g
/min)
1.5 2 2.5 3 3.5 422
24
26
28
30
32
34
36
38
D2R VS(Bmax/Kd)
Meta
bolis
m OF
C(m
icrom
ol/10
0g/m
in)
1.5 2 2.5 3 3.5 430
35
40
45
50
D2R VS(Bmax/Kd)
Meta
bolis
m Pr
efro
ntal
(micr
omol/
100g
/min)
3035
40
45
50
55
60
65
1.8
2 2.2
2.4
2.6
2.8
3 3.2
3.4
ControlControl Cocaine Abuser Cocaine Abuser
DA D2 receptors
Relationship Between Brain Glucose Metabolism and Striatal D2 Receptors
Volkow et al., PNAS 2011 108(37): 15037-42
ACGACG
OFCOFCSCCSCC
HippHipp
NAccNAccVPVP
AmygAmyg
REWARDREWARD
INHIBITORY CONTROL
INHIBITORY CONTROL
MEMORY/LEARNING MEMORY/
LEARNING
EXECUTIVEFUNCTIONEXECUTIVEFUNCTION
PFCPFC
Becomes severely disrupted in ADDICTION
MOTIVATION/DRIVE
MOTIVATION/DRIVE
The fine balance in connections that normally exists between brain areas active in reward, motivation, learning and memory, and inhibitory control
DriveOFCDriveOFC
Saliency NAcSaliency NAc
MemoryAmygdalaMemoryAmygdala
Control CG Control CG
Non-Addicted Brain
Non-Addicted Brain
AddictedBrain
AddictedBrain
STOP STOP
GOGODriveDrive
MemoryMemory
Saliency Saliency
ControlControl
DriveDrive
MemoryMemory
Saliency Saliency
Stress Reactivity
Stress Reactivity
Effective Strategies Attend to Multiple Aspects
of Addiction:
• Behavior
• Biology
• Social Context
A Double Blind, Placebo Controlled Trial Of NEPICASTAT
(Dβh Inhibitor) In Cocaine Dependence[Biotie/NIDA]
Nepicastat attenuates cue-induced reinstatement of
cocaine seekingSchroeder et al.,
Neuropsychopharmacology. 2013Devoto et al., Addict Biol. 2013
Nepicastat increases DA in PFC (but not in Nac)
Improving Prefrontal Function
NIDA Criminal Justice Drug
Abuse Treatment Studies (CJ-DATS)
NIDA Criminal Justice Drug
Abuse Treatment Studies (CJ-DATS)
National Drug Abuse
Treatment Clinical Trials
Network (CTN)
National Drug Abuse
Treatment Clinical Trials
Network (CTN)
Research Centers
CTN SitesCTN Sites
• 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
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;33:7420-7427
Brain and Behavioral Impact of Televised
Anti-Tobacco Public Service Announcements: Predictive Value
Addressing Drugs and Crime
Public Health Approach - disease - treatment
Public Safety Approach - illegal behavior - punish
High Attrition High Recidivism
Successful Reentry Programs Use an Integrated Public Health-Public
Safety Strategy
Blends functions of criminal justice and treatment systems
to optimize outcomes
Community-based treatment
Opportunity to avoid incarceration or criminal record
Close supervision
Consequences for noncompliance are certain and immediate
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.
www.drugabuse.gov