1. Rx Drug Abuse
Where is Science Leading Us?
Nora D. Volkow, M.D.
Director

2. Analgesic Mechanisms of Mu Opiate Drugs
(Heroin, Vicodin, Morphine)
Pain
Ascending
input
Descending
modulation
Dorsal
horn
Dorsal root
ganglion
Peripheral
nerve
Spinothalmic
Tract
Peripheral nociceptors
Trauma
Opioids
Alpha2 agonists
Local anesthetics
Anti-inflammatory
drugs
Local anesthetics
Opioids
Alpha2 agonists
Local anesthetics
Thalamus
(pain)
ACC
(pain)
PAG
(pain)
Accumbens
(reward)

3. Numbers in Millions
Prescription Drug Misuse/Abuse is a
Major Problem in the US
Source: SAMHSA, 2013 National Survey on Drug Use and Health, 2014.
0.3
0.5
1.3
1.5
6.5
19.8
24.6
0 10 20 30
Heroin
Inhalants
Hallucinogens
Cocaine
Psychotherapeutics
Marijuana
IllicitDrugs
4.7
4.9
5.1 5
4.8 4.9 4.8
4.3
4.8
4.2
2.1 2.2 2.1 2.1 2
2.2 2.2
2
2.3
2
1.2 1.1
1.4
1.2 1.1 1.2 1.1 1
1.3 1.3
0.3 0.3 0.4 0.3 0.2 0.3 0.4
0.2 0.2 0.2
0
1
2
3
4
5
6
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Current Drug Use Rates in
Persons Ages 12+
Percent
Past Year Nonmedical Use of Types
of Psychotherapeutic Drugs among
Persons Aged 12 or Older: 2004-2013

4. High Levels of Opioid Prescriptions have Facilitated Diversion of
Opioids and Contributed to Overdose Deaths
4,030
4,400
5,528
7,456
8,517
9,857
10,928
13,723
14,408
14,800
15,597
16,65116,917
16,00716,235
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
18,000
Rx Opioid Overdose Deaths
Total Female Male
Source: CDC Wonder
Oxycodone and Hydrocodone Prescriptions
16 19 22 25 27 29 31 34 38
43 47 49
54 57 57
72
83
90
96
101
106 110
120
126
132 133 130 131
136 134
0
20
40
60
80
100
120
140
160
Millions
Oxycodone (Schedule II)
Hydrocodone…
SDI Health, VONA_02-1-13_Opioids Schedule II & III

5. Past Month &Past Year Heroin Use
Persons Aged 12 or Older
SAMHSA, 2012 National Survey on Drug Use and Health, 2014.
404
314
398
379
560
373
455
582
621 620
669 681
166
119
166
136
339
161
213
193
239
281
335
289
0
100
200
300
400
500
600
700
800
200220032004200520062007200820092010201120122013
Past Year
Past Month
NumbersinThousands
1,960 1,842 1,779
2,089 2,080
1,878 2,009 2,088
2,399
3,041
3,278
3,036
4,397
5,925
8,257
0
1,000
2,000
3,000
4,000
5,000
6,000
7,000
8,000
9,000
Heroin Overdose Deaths
Total Female Male
Source: CDC Wonder
Abuse of Opioid Medications has led to a Rise in Heroin
Abuse and Associated Deaths from Overdoses

6. How Can Research Help?
• PAIN: Develop less abusable analgesics and
alternative therapeutics
• OVERDOSES: User Friendly Naloxone
• ADDICTION: New Medications and Immunotherapies
• Pharmacogenomics (precision medicine)
• Implementation science

7. Abuse-Resistant Opioid Prodrug
(i.e., Signature Therapeutics)
PAIN: Less Abusable Analgesics

8. Technologies For Invasive & Non-invasive Neuromodulation
Transcranial Direct
Current Simulation (tDCS)
passes direct current though
two electrodes
High-Definition transcranial
Direct Current Stimulation (HD-
tDCS) uses arrays of scalp electrode to
guide current to brain structures
Morena-Duarte I et al., Neuroimage 2014; 85(3): 1003-1013.
Non-Medication Strategies
For the Treatment of PAIN and ADDICTION
Left sensory thalamusLeft periventricular gray
Gray AM et al., J Pain
2014; 15(3): 283-292.
Deep Brain Stimulation (DBS)
Stereotaxtic implantation of
electrodes that emit electrical
stimulation to a targeted
neuronal region
Transcranial Magnetic
Stimulation (TMS)
Magnets induce current in the brain

9. How Can Research Help?
• PAIN: Develop less abusable analgesics and
alternative therapeutics
• OVERDOSES: User Friendly Naloxone
• ADDICTION: New Medications and Immunotherapies
• Pharmacogenomics (precision medicine)
• Implementation science

10. NIDA-Sponsored User Friendly Naloxone
(nasal spray)
• AntiOp, developing a single-dose, disposable
naloxone nasal spray
• Investigational New Drug (IND) application
filed in 2012
• Product could be on the market 2015
• Lightlake Therapeutics, conducting clinical trials
with intranasal naloxone for binge eating disorder
will test this technology for the treatment of opioid
overdose
• Clinical trials began 2012

11. How Can Research Help?
• PAIN: Develop less abusable analgesics and
alternative therapeutics
• OVERDOSES: User Friendly Naloxone
• ADDICTION: New Medications and Immunotherapies
• Pharmacogenomics (precision medicine)
• Implementation science

12. Opioid Agonist Treatments
Decreased Heroin OD Deaths
Baltimore, Maryland, 1995-2009
#OverdoseDeaths
#PatientsTreated
Heroin overdoses
Buprenorphine patients
Methadone patients
RCT of Buprenorphine Implants
compared with Placebo & Sublingual
Buprenorphine/Naloxone
for Opioid Addiction
Rosenthal RN et al., Addiction 2013;105: 2141-2149.
Buprenorphine Implants
% of Urines Negative (out of 72) for Opioids Across Weeks 1 to 24
%ofPatientsFailingtoExceed
EachPossibleCriterionofSuccess
Placebo
Sublingual
Buprenorphine
Challenge: Compliance with daily intake
Solution: Can one develop long acting medications
Schwartz RP et al., Am J Public Health 2013.

13. Heroin Anti-Heroin
Antibodies
Developing Vaccines to Block Heroin’s Effects
HEROIN CAN NOT ENTER THE BRAINHEROIN RAPIDLY ENTERS THE BRAIN

14. How Can Research Help?
• PAIN: Develop less abusable analgesics and
alternative therapeutics
• OVERDOSES: User Friendly Naloxone
• ADDICTION: New Medications and Immunotherapies
• Pharmacogenomics (precision medicine)
• Implementation science

15. • Responsible Prescribing and Management
of Chronic Pain, which requires enhanced
Education on Pain and its Treatment
• Availability of Naloxone
• Mandatory Addiction Education in Medical,
Nursing and Pharmacy Schools
Strategies that Can Help Address the Dangers of
Opioid Overdose and Addiction in the US

16. National Pain Strategy
”HHS Secretary
should develop a
comprehensive,
population health-
level strategy for
pain prevention,
treatment,
management,
education,
reimbursement
and research ..."
ORWH
OBSSR
NIDA
NIDCR
NINDS
NIA
NINR
NICHD
NIAMS
NCCIH
NIH Pain Consortium Centers
of Excellence in Pain Education
Goal: Improve pain treatment
through education

17. 25%
9%
17%
9%
16% 19%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
% Treatment Programs
Offering FDA-approved
SUD Medications
Methadone
26.4%
Buprenorphine
3.9%
Vivitrol
0.3%
Not receiving
Methadone,
Buprenorphine,
or Vivitrol
69.4%
% OTP patients receiving
methadone, buprenorphine, or
vivitrol
Knudsen et al, 2011, J Addict Med
• 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
Resources for Medical Students,
Resident Physicians & Faculty
NIDA

18. Questions