1. Treating DRUG ADDICTION: What Do We Know? What More Should We Do?
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
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

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

3. ADDICTION IS A DEVELOPMENTAL DISEASE
starts in adolescence and childhood
1.6%
Prefrontal
Cortex
Amygdala
1.4%
1.2%
1.0%
% in each age group who develop first-time cannabis use disorder
0.8%
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, , 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

4. Drugs and Natural Rewards ACTIVATE Dopamine in Reward Regions
VTA/SN
nucleus
accumbens
frontal
cortex
100
200
300
400
500
600
700
800
900
1000
1100 1 2 3 4
5 hr
Time After Amphetamine
% of Basal Release
AMPHETAMINE 50
100
150
200 60
120
180
Time (min)
% of Basal Release
Empty
Box
Feeding
Di Chiara et al.
FOOD
Drugs of abuse increase DA in the
Nucleus Accumbens, which is believed
to trigger the neuroadaptions
that result in addiction

5. Repeated Drug Use Changes the Brain Weakens the Brain Dopamine System
Control
Cocaine Abuser T Y R O S I N E D A P DA
COCAINE T Y R O S I N E D A P DA T Y R O S I N E D A P DA
PLEASURE
REPEATED USE OF COCAINE OR OTHER DRUGS REDUCES LEVELS OF DOPAMINE D2 RECEPTORS

6. Dopamine D2 Receptors are Lower in Addiction
Normal Controls
1.5 2
2.5 3
3.5 4
4.5 15 20 25 30 35 40 45 50
DA D2 Receptors
(Ratio Index)
Cocaine Abusers
Cocaine
Meth
DA D2 Receptor Availability
1.6
1.8 2
2.2
2.4
2.6
2.8 3
3.2`
Alcohol
Bmax/Kd
Heroin 20 25 30 35 40 45 50
control
addicted
Volkow et al., Neuro Learn Mem 2002.

7. Effects of Tx with an Adenovirus Carrying a DA D2 Receptor Gene into NAc in DA D2 Receptors
Overexpression of
DA D2 receptors
reduces alcohol
self-administration 60
1st D2R Vector
p <
2nd D2R Vector 50
p < 40
p < 0.005
p < 0.005
Percent Change in D2R 30 20
p < 0.10 10
Null Vector 4 6 8 10 24
-20 DA DA
% Change in Alcohol Intake
-40
p < 0.01 DA DA
p < 0.01 DA
-60 DA
p < 0.001 DA DA
-80
p < 0.001
p < 0.001
-100 4 6 8 10 24
Thanos, PK et al., J Neurochem, 78, pp , 2001.
Time (days)

8. Brain glucose metabolism
Low Levels of Striatal D2 Receptors Are Associated with Impaired Activity in Frontal Regions
Control
Cocaine Abuser 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 addicted
Brain glucose metabolism
Controls
Methamphetamine
Abusers
umol/100gr/min
OFC 4
Controls
Alcoholics
Volkow et al., PNAS (37):
DA D2 receptors

9. ADDICTION CAN BE TREATED
Partial Recovery of Brain Dopamine Transporters
in Methamphetamine (METH)
Abuser After Protracted Abstinence 3
ml/gm
Normal Control
METH Abuser
(1 month detox)
METH Abuser
(14 months detox)
Source: Volkow, ND et al., Journal of Neuroscience 21, , 2001.

10. 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
Outpatient Rehab
Inpatient Rehab
Outpatient Mental
Health Center
Hospital Inpatient
Doctor’s Office
Emergency Room
Prison or Jail
2.1
1.5
1.0
1.0
0.8
0.7
0.6
0.4
Numbers in Millions
Source: 2012 NSDUH, National Findings, SAMHSA, OAS, 2013.

11. Pre - - Post During Pre - - - - - - - - - - - - Post
Evaluation of A Hypothetical Treatment 10
HYPERTENSION 9 8
Pre Post
During 7
Symptom Severity 6 5 4 3 2
Just Like Hypertension,
Addiction Is A
Chronic Disease That
Requires Continued Care 1
Pre
During
During
During
Post 10
ADDICTION 9
Pre Post 8 7 6
Symptom Severity 5 4 3 2 1
Pre
During
During
During
Post
Stage of Treatment
Source: McLellan, AT, Addiction 97, , 2002.

12. 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 

13. Medications for Opioid Addiction
antagonist
agonist
Full Agonist
(Methadone)
Opioid Effect
no effect
Partial Agonist
(Buprenorphine)
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
an agonist drug has an
active site of similar shape
to the endogenous ligand
so binds to the receptor
and produces the same effect
Antagonist
(Naloxone)
Log Dose
Source: SAMHSA, 2012 National Survey on Drug Use and Health, 2013.

14. Opioid Agonist Treatments Decreased Heroin Overdose Deaths
Baltimore, Maryland,
Overdose Deaths, No.
Patients Treated, No.
Heroin overdoses
Buprenorphine patients
Methadone patients
Schwartz RP et al., Am J Public Health 2013;1 03:

15. Methadone Maintenance Therapy Improves HIV Outcomes in IDU
Methadone Maintenance Therapy Promotes Initiation Of Antiretroviral Therapy IDU
Antiretroviral Adherence and HIV Treatment Outcomes Among HIV/HCV Co-Infected IDU: Role of Methadone
Adjusted Odds Ratio
Uhlmann S et al., Addiction 2010; 105(5):
Palepu A et al., Drug and Alcohol Dependence 2006; 84:

16. 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
Opioid Tx Meds:
Methadone
7.8
41.3
Buprenorphine
20.9
37.3
Tablet naltrexone
22.0
10.9
Knudsen et al, 2011, J Addict Med; 5:21-27.

17. 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
5.4
2.3
Number of days of illicit opiate use per week
0.9
5.6
2.4
D’Onofrio JAMA

18. Medications Are An Important Part Of
Treatment For Many Drug Abusing Offenders
Methadone Maintenance For Prisoners:
Results At 12 Months Post-release
In Treatment
for one year at 12 months post-release
The data are from the first 100 participants in the Prison Methadone study.
The proportions of participants in treatment at 1-month post-release are:
-Counseling only, 9%
-Counseling+ Transfer, 42%
-Counseling + Methadone, 65%
Chi-square goodness-of-fit tests found that there were significant differences between Counseling Only and Counseling+Methadone (p<.001) and Counseling+Transfer (p<.01).
The proportion of participants testing positive for opiates are:
-Counseling only, 76%
-Counseling + Transfer, 50%
-Counseling + Methadone, 34%
Chi-square goodness-of-fit tests found significant differences between Counseling Only and Counseling + Methadone (p<.05).
Opiate + Urine Test at 12 months post release
C = Counseling Only;
C+T = Counseling & Transfer
C+M = Counseling & Methadone
Kinlock T, et al. J Subst Abuse Treatment 2009.

19. Challenge: How to Integrate Drug Abuse & Addiction
Screening, Prevention & Treatment
into the Healthcare System

20. Interventions Tailored to Severity
In Treatment ~ 2,300,000
Addiction ~ 23,000,000
Before we talk about the specific priorities in the Strategy it is important to understand the full spectrum of the Substance USE problem in our country; different policies are needed for different parts of the overall problem This pyramid describes this very well
1 – As represented by the broad base of this pyramid –most people in the US either do not use substances or use them very very few times - Here the best policies are prevention – to keep use low
2 – As you go up the pyramid to the wavy dotted line – this shows when “use” becomes “harmful use” – either to an individual’s health or their productivity or their relationships. It is NOT a diagnosis and people can go back and forth across that line – but there are a lot of these folks about 65 – 70 million They are the people who drink and drive, or make their asthma problem worse by smoking marijuana, or are failing school because of too much weekend partying with drugs. Here we need convenient, attractive, potent but probably brief interventions to reduce use and prevent problems from becoming worse
3 –The bright solid line means that the frequency and intensity of use has reached a DIAGNOSTIC threshold – there are 23 – 25 million adults who meet diagnostic criteria for the most serious problems “SUSTANCE ABUSE AND DEPENDENCE” - Click – In comparison, most people think there is an “epidemic” of diabetes and there is - about 24 million people are diabetic.
4 - The orange pinnacle shows the number of people who are receiving any kind of treatment – about 2.3 – 2.5 million or only 1/10 of those who meet the diagnosis – even smaller proportion of those with “harmful use” – This is the “Treatment GAP” that we want to close – the worst in all of medicine
5 – The OVAL indicates that we need policies and interventions that will reach a FAR broader range of people with “substance use problems”
Severity
“Harmful – 40,000,000
Use”
Little or No Use
McLellan and Woodworth Journal of Substance Abuse Treatment, Volume 46, Issue 5, 2014, 20

21. Integration of Substance Use Disorders Into Healthcare System
SUDs are too omnipresent, dangerous & expensive in healthcare to be ignored
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
Mainstream healthcare needs to prepare for this
Integrate with specialty service

22. 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

23. GO Addicted Brain STOP Non-Addicted Brain Memory Memory Drive Drive
Saliency
Control
Drive
OFC
Saliency
NAc
Memory
Amygdala
Control CG
Drive
Memory
Saliency
STOP GO
Adapted from: Volkow et al.,
J Clin Invest 111(10): , 2003.