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National Institute on Drug Abuse
Bringing the full power of science to bear on drug abuse and addiction
Nora D. Volkow, M.D.
Director
National Institute on Drug Abuse
Nora D. Volkow, M.D.
Director
ADDICTION IS A DISEASE OF THE BRAIN
as other diseases it affects the tissue function
Decreased Brain Metabolism in Drug Abuse Patient
High
Control
Cocaine Abuser
Decreased Heart Metabolism in Heart Disease Patient
Low
Healthy Heart
Diseased Heart
Sources: From the laboratories of Drs. N. Volkow and H. Schelbert
% in each age group who develop firsttime cannabis use disorder
ADDICTION IS A DEVELOPMENTAL DISEASE
starts in adolescence and childhood
1.6%
Prefrontal
Cortex
1.4%
1.2%
1.0%
0.8%
Amygdala
0.6%
Brain areas where volumes are smaller
in adolescents than young adults
0.4%
0.2%
Sowell, E.R. et al., Nature Neuroscience, 2, 859-861, 1999
0.0%
5
10 15 18
25 30 35 40 45 50 55 60 65 70
Age
Age at cannabis use disorder as per DSM IV
NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003
% of Basal Release
Drugs and Natural Rewards ACTIVATE
Dopamine in Reward Regions
frontal
cortex
nucleus
accumbens
1100
1000
900
800
700
600
500
400
300
200
100
0
AMPHETAMINE
0
VTA/SN
1
2
3
4
Time After Amphetamine
FOOD
% of Basal Release
200
Drugs of abuse increase DA in the
Nucleus Accumbens, which is believed
to trigger the neuroadaptions
that result in addiction
5 hr
150
100
50
0
Empty
Box Feeding
0
60
120
180
Time (min)
Di Chiara et al.
Repeated Drug Use Changes the Brain
Weakens the Brain Dopamine System
Control
Cocaine Abuser
TYROSINE
TYROSINE
TYROSINE
DOPA
DOPA
DOPA
DA
DA
DA
DA
DA
DA
DA
DA
DA
DA
DA
DA
DA
COCAINE
DA
DA
DA
DA
DA
DA
DA
DA
DA
DA
DA DA
PLEASURE
REPEATED USE OF COCAINE OR OTHER DRUGS REDUCES
LEVELS OF DOPAMINE D2 RECEPTORS
Dopamine D2 Receptors are Lower in Addiction
Normal Controls
Cocaine Abusers
4.5
4
DA D2 Receptors
(Ratio Index)
Cocaine
3.5
3
2.5
2
Meth
1.5
15
20
25
30
35
40
45
50
3.2`
3
2.8
Bmax/Kd
Alcohol
2.6
2.4
2.2
2
1.8
1.6
Heroin
20
control
addicted
25
30
35
40
45
Volkow et al., Neuro Learn Mem 2002.
50
50
40
2nd D2R Vector
60
p < 0.0005
p < 0.0005
p < 0.005
30
20
p < 0.005
p < 0.10
10
0
0
4
6
8
10
24
0
Null Vector
Percent Change in D2R
Overexpression of
DA D2 receptors
reduces alcohol
self-administration
1st D2R Vector
Effects of Tx with an Adenovirus Carrying a DA D2
Receptor Gene into NAc in DA D2 Receptors
-20
-40
p < 0.01
p < 0.01
-60
p < 0.001
-80
-100
p < 0.001
p < 0.001
0
Thanos, PK et al., J Neurochem, 78, pp. 1094-1103, 2001.
4
6
8 10
Time (days)
24
Low Levels of Striatal D2 Receptors Are Associated with
Impaired Activity in Frontal Regions
65
60
50
45
Control
umol/100gr/min
40
OFC
addicted
Brain glucose metabolism
55
35
30
1.8
90
2
2.
2
2.4
2.
6
2.8
3
3.2
3.
4
80
70
60
40
35
30
30
2.9
3
3.1
3.2
3.3
3.4
3.5
3.6
36
34
32
30
28
26
24
2
2 .5
3
3 .5
4
Volkow et al., PNAS
D2R 2011
VS 108(37): 15037-42
4
50
38
22
1 .5
Methamphetamine
Abusers
Controls
Metabolism Prefrontal
(micromol/100g/min)
45
40
Metabolism OFC
(micromol/100g/min)
control
50
50
25
1 .5
Cocaine Abuser
45
40
0
35
Controls
30
2
2 .5
3
3 .5
D2 Receptors
(BP )
D2R VS ND
4
1 .5
Alcoholics
2
2 .5
3
3 .5
VS
DA D2D2R
receptors
(Bmax/Kd)
4
ADDICTION CAN BE TREATED
Partial Recovery of Brain Dopamine Transporters
in Methamphetamine (METH)
Abuser After Protracted Abstinence
3
0
ml/gm
Normal Control
METH Abuser
(1 month detox)
METH Abuser
(14 months detox)
Source: Volkow, ND et al., Journal of Neuroscience 21, 9414-9418, 2001.
Opportunities with Health Care Reform to
Expand Involvement of the Health Care System
in Treatment of SUD
In 2012 An Estimated
22.2 Million Americans
12 or Older Were Dependent On
Any Illicit Drugs or Alcohol
But …Only 4 Million (18%)
of These Individuals
Had Received Some Type of
Tx In the Past Year and Few
involved Health Care Systems
Location TX Received
Self Help Group
2.1
Outpatient Rehab
1.5
Inpatient Rehab
1.0
Outpatient Mental
Health Center
1.0
0.8
Hospital Inpatient
0.7
Doctor’s Office
0.6
Emergency Room
Prison or Jail
0.4
0
.5
1.0
1.5
2.0
Numbers in Millions
Source: 2012 NSDUH, National Findings, SAMHSA, OAS, 2013.
2.5
Evaluation of A Hypothetical Treatment
Symptom Severity
10
HYPERTENSION
9
8
7
6
5
4
3
2
1
0
Pre
During
Symptom Severity
10
During
During
Post
ADDICTION
9
8
7
Just Like Hypertension,
Addiction Is A
Chronic Disease That
Requires Continued Care
6
5
4
3
2
1
0
Pre
During
During
During
Stage of Treatment
Post
Source: McLellan, AT, Addiction 97, 249-252, 2002.
ADDICTION TREATMENT
Addiction is a chronic disease and requires continued
care
No single treatment is appropriate for everyone
Medications are an important element of treatment for many patients,
Drug use during treatment must be monitored continuously, as lapses
during treatment occur and need to be addressed
Attends to multiple needs of the individual,
including co-morbid
mental illness and infectious diseases (HIV, HCV, HBV, TB)
Treatment does not need to be voluntary to be effective
Medications for Opioid Addiction
agonist
antagonist
no effect
effect
an agonist drug has an
active site of similar shape
to the endogenous ligand
so binds to the receptor
and produces the same effect
an antagonist drug is close
enough in shape to bind to the
receptor but not close enough
to produce an effect. It also
takes up receptor space and so
prevents the endogenous
ligand from binding
Opioid Effect
Full Agonist
(Methadone)
Source: SAMHSA, 2012 National Survey on Drug Use and Health, 2013.
Partial Agonist
(Buprenorphine)
Antagonist
(Naloxone)
Log Dose
Opioid Agonist Treatments Decreased
Heroin Overdose Deaths
Heroin overdoses
Buprenorphine patients
Methadone patients
Schwartz RP et al., Am J Public Health 2013;1 03: 917-922.
Patients Treated, No.
Overdose Deaths, No.
Baltimore, Maryland, 1995-2009
Methadone Maintenance Therapy
Improves HIV Outcomes in IDU
Antiretroviral Adherence and HIV
Treatment Outcomes Among HIV/HCV
Co-Infected IDU: Role of Methadone
Adjusted Odds Ratio
Methadone Maintenance Therapy
Promotes Initiation Of
Antiretroviral Therapy IDU
Uhlmann S et al., Addiction 2010; 105(5):907-913.
Palepu A et al., Drug and Alcohol Dependence 2006; 84: 188-194.
Implementation research
Lack of uptake of medication-assisted treatment
TOO FEW ARE TREATED
Addiction Specialty
Programs Offering
Services
As % of all
programs
surveyed
(N=345)
Within adopting
programs, % of
eligible patients
receiving Rx
Methadone
7.8
41.3
Buprenorphine
20.9
37.3
Tablet naltrexone
22.0
10.9
Opioid Tx Meds:
Knudsen et al, 2011, J Addict Med; 5:21-27.
ED-initiated Buprenorphine Increased Engagement In
Addiction Treatment, Reduced Self-reported Illicit Opioid Use,
& Decreased Use Of Inpatient Addiction Treatment Services
% engaged in treatment on the
30th day after randomization
D’Onofrio JAMA. 2015.
100
90
80
70
60
78%
5.4
5.6
5.4
50
40
2.3
30
20
0.9
37%
45%
2.4
10
0
Buprenorphine
Referral
Brief Intervention
Number of days of illicit opiate use per week
Medications Are An Important Part Of
Treatment For Many Drug Abusing Offenders
Methadone Maintenance For Prisoners:
Results At 12 Months Post-release
80%
70%
60%
50%
40%
30%
20%
10%
0%
-10%
66%
49%
37%
25%
17%
0%
C
In Treatment
for one year at 12
months post-release
Opiate + Urine Test at
12 months post release
C+T
C+M
C = Counseling Only;
C+T = Counseling & Transfer
C+M = Counseling & Methadone
Kinlock T, et al. J Subst Abuse Treatment 2009.
Challenge: How to Integrate Drug Abuse & Addiction
Screening, Prevention & Treatment
into the Healthcare System
Interventions Tailored to Severity
In Treatment ~ 2,300,000
Addiction ~ 23,000,000
“Harmful – 40,000,000
Use”
Little or No Use
McLellan and Woodworth Journal of Substance Abuse
Treatment, Volume 46, Issue 5, 2014, 541 - 545
Integration of Substance Use Disorders
Into Healthcare System
1. SUDs are too omnipresent, dangerous &
expensive in healthcare to be ignored
2. Market forces will accelerate integration
• 2008 Parity Law providing for coverage of SUD at
level of other medical diseases
• 2010 Healthcare reform provides insurance to
individuals with SUD that in the past would have not
had access to healthcare
3.Mainstream healthcare needs to prepare for this
• Integrate with specialty service
Resources for Medical Students,
Resident Physicians & Faculty
• NIDA CoEs established in 2007 to help fill gaps in
medical education curricula related to both illicit drugs
and Rx drug abuse
• Medical schools at CoEs have developed a diverse
portfolio of innovative curriculum resources about how
to identify and treat patients struggling with SUD
Addicted Brain
Non-Addicted Brain
Control
Control
CG
STOP
Saliency
NAc
Drive
OFC
Memory
Amygdala
Adapted from: Volkow et al.,
J Clin Invest 111(10):1444-1451, 2003.
Saliency
Drive
GO
Memory