The Presidents Opioid Initiative

Actions across federal, state, local governments

and the private sector

Improve Prescriber
Training

Train
Train >540,000
>540,000 health
health care
care
providers
providers
Double
Double PDMP
PDMP registration
registration
Reach
Reach >4M
>4M providers
providers with
with
appropriate
appropriate prescribing
prescribing practices
practices
messaging
messaging

Commitments from:

Improve Access to
Treatment

Double
Double number
number of
of buprenorphine
buprenorphine
prescribers
prescribers
Double
Double number
number of
of naloxone
naloxone
providers
providers
Reach
Reach >4M
>4M providers
providers with
with opioid
opioid
abuse
messaging
abuse messaging

Over
Over 40
40 provider
provider groups,
groups, including
including physicians,
physicians, dentists,
dentists, advanced
advanced practice
practice
registered
nurses,
physician
assistants,
physical
therapists
and
educators
registered nurses, physician assistants, physical therapists and educators
CVS
CVS Health,
Health, Rite
Rite Aid
Aid and
and several
several pharmacy
pharmacy and
and pharmacist
pharmacist organizations
organizations
(naloxone,
(naloxone, PDMPs)
PDMPs)
CBS,
CBS, ABC,
ABC, The
The New
New York
York Times,
Times, Google,
Google, the
the National
National Basketball
Basketball Association,
Association, and
and
Major
League
Baseball
will
donate
media
space
for
PSAs
Major League Baseball will donate media space for PSAs

Science = Solutions

Wilson M. Compton, M.D., M.P.E.

Deputy Director
National Institute on Drug Abuse
Science =
Solutions

The NIH Mission is

To seek fundamental knowledge
about the nature and behavior of
living systems and the application of
that knowledge to enhance health,
lengthen life, and reduce illness and
disability.
Worlds largest source of funding
for biomedical research
Support more than 300,000
research personnel at over 3,000
universities and research
institutions
27 Institutes and Centers (ICs)
with specific research agendas

Science =
Solutions

Office of Diversity
& Health
Disparities

Office of
the
Director

AIDS Research
Program

Office of
Office of
Intramural
Manageme Science Policy & Research
nt
Communications Program

Center for the

Clinical Trials
Network

Division of
Therapeutics
and Medical
Consequences

Office of
Translational
Initiatives and
Program
International
Innovations
Program

Division of
Extramural
Research

Division of
Neuroscience
and Behavior

Division of
Epidemiology,
Services and
Prevention
Research

FY2016 Operating Plan: $1,050,550 ($756,306 non-AIDS,

$294,244 AIDS)

Released December 2015

Science =

The NEW ENGLAND JOURNAL of MEDICINE

Key Drug
Abuse Public
Health Crisis

REVIEW ARTICLE

Relationship between Nonmedical

Prescription-Opioid Use and Heroin use
Wilson M. Compton, M.D., M.P.E., Christopher M. Jones, Pharm.D, M.P.H.
and Grant T. Baldwin, Ph.D., M.P.H.

January 14, 2016

Opioid Drug Abuse:

Prescription Opioids AND
Heroin
JAMA
The Journal of the
American Medical Association
October 13, 2015

Original Investigation

Nonmedical Prescription Opioid Use and Use Disorders

Among Adults Aged 18 Through 64 Years in the United States,
2003-2013
Beth Han, MD, PhD; Wilson M. Compton, MD, MPE; Christopher M. Jones, PharmD, MPH; Rong Cai, MS

High Levels of Opioid Prescriptions have

Facilitated Diversion & Contributed to
Overdose Deaths
Near Tripling of Opioid

Prescriptions from U.S. Retail

Pharmacies, 1991-2013

Total Rx Opioid
Tablets Dispensed in
Retail Pharmacies in
USA:
the
2013

15,972,304,698
2014
Source: Jones CM, et al. JAMA Internal
Medicine 2016: doi:
10.1001/jamainternmed.2015.7799

15,606,882,755

IMS Health, Vector One: National, 19912011

IMS Health, National Prescription Audit, 20122013

Marked Increases in Prescription Opioid

and Heroin Overdose Deaths in the USA
2000 to Any
2014
opioid
30,000

USA 2014
Overdose Deaths:
25,000
47,055 Any Drug
27,119
Any
20,000
Opioid
Number of Deaths
18,893 Rx
opioid
15,000
10,574 Heroin
10,000

5,000
0

Source: CDC, NVSS 2000-2014

Marked Geographic Variation in Mortality:

Estimated Age-adjusted Death Rates for Drug
Poisoning by County

199
9
Designed by L. Rossen, B.
Bastian & Y. Chong. SOURCE:
CDC/NCHS, National Vital
Statistics System; Tom Frieden
Presentation at the Opioid
Summit, Atlanta, April 2016

Marked Geographic Variation in Mortality:

Estimated Age-adjusted Death Rates for Drug
Poisoning by County

201
4
Designed by L. Rossen, B.
Bastian & Y. Chong. SOURCE:
CDC/NCHS, National Vital
Statistics System; Tom Frieden
Presentation at the Opioid
Summit, Atlanta, April 2016

High and Slightly Decreasing Rates of Rx

Opioid Abuse :
12-Month Prevalence of Rx Opioid Misuse, USA
Ages 18-64, 2003-2014

7.0
6.0
5.0

% 4.0
3.0

Any Rx Opioid
Use

Trend, p < .
001

2.0
1.0
0.0

Data sources: Han, Compton et al. JAMA October 13, 2015; SAMHSAs
National Survey on Drug Use and Health (NSDUH) data, 2003-2014,
Science =
adults aged 18-64 in the United States.
Solutions

Increasing Intensity of Opioid

Misuse:
12-Month Prevalence of Rx Opioid Misuse without
Frequent Use or Ab/Dep, Rx Opioid Ab/Dep, 100+ days
Rx Opioid in USA Ages 18-64, 2003-2014
5.0
4.0

% 3.0
2.0

Rx Opioid Use Without 100+ or

Ab/Dep
Opioid Ab/Dep
100+ Days

Trends, p < .
001

1.0
0.0
Data sources: Han, Compton et al. JAMA October 13, 2015; SAMHSAs
National Survey on Drug Use and Health (NSDUH) data, 2003-2014,
Science =
adults aged 18-64 in the United States.
Solutions

People Abusing Analgesics DIRECTLY &

INDIRECTLY Obtain Them by

Prescription: Most Recent Pill Source
Source Where Respondent Age 12+ Obtained
Analgesics:

More than
One Doctor
One Doctor (2.6%)
(21.2%)

Source Where Friend/Relative Obtained

More than
One Doctor
(3.3%)
Free from
Friend/Rela
tive
One Doctor
(5.1%)
Bought/Took
(83.8%)
from
Friend/Relativ
Drug
Dealer/
e (4.9%)
Stranger
Bought (1.4%)
on Internet
(0.3%)
1
Other category includes Wrote Fake Prescription," "Stole from Doctors
Other1
Office/Clinic/Hospital/Pharmacy," and "Some Other Way."
(1.2%)
Source: SAMHSA, 2012 and 2013 National Survey on
Drug Use and Health

Other1
Free
(4.3%)
from
Bought on
Friend/
Internet
Relative
(0.1%)
(53.0%)
Drug
Dealer/
Stranger
(4.3%)
Bought/Took
from
Friend/Relative
(14.6%)

Increasing Neonatal Abstinence

Syndrome
NICU Admissions
for NAS (Number
per 1000
Admissions)

Source: Tolia VN, Patrick SW, et al. NEJM 2015;372:2118-2126

Increasing
NAS:
West Virginia
2007-2013

Source: Stabler ME, et al. Journal of Rural Health

2016; 1-10

Opioid Treatment During Pregnancy:

MOTHER Study RCT (N = 175)
Mean Neonatal Morphine Dose, Length of Neonatal
Hospital Stay, and Duration of Treatment for Neonatal
Abstinence Syndrome

All p < .01

Source: Jones HE et al. N Engl J Med 2010;363:2320-2331.

Science =
Solutions

Outbreak of HIV Linked to

IDU of Oxymorphone in
Indiana, 2015
162 HIV Infections in a Community of 4200
84.4%

80; 80%
108

3%
17%

114

co-infected with Hepatitis C

Injection Drug Use

No Injection Drug
Use
Status Not
Determined

109

121 47%
HIV- 53%

61.7
230
tested

4
247

located

Reported average
of 9 syringe-sharing
partners, sex partners,
or other social contacts
at risk for HIV infection
contacts

74

4.6

social contact
regarded as a
high risk for
HIV

54
57.8 42.2

syringe-sharing
or sex partners

112
All reported injecting
tablets of oxymorphone
As drug of choice

HIV+

128

373

not located

Science = Solutions : Using

Research to Improve HIV and
Hepatitis C in Rural Areas
NIH is partnering with the Appalachian Regional Commission
to fund grants to address increased opioid injection drug use
and resulting overdose, HIV and Hepatitis C infection.
One-year research planning grants to:

Improve understanding problems scope; contributing health trends

Identify resources, obstacles

Goal: build foundation for better intervention programs,

larger-scale research efforts to address this public

health threat
Applications now being accepted

RFA-DA-16-015: Due April 28

http://grants.nih.gov/grants/guide/rfa-files/RFA-DA-16015.html

Most Heroin Users Report

Previous Non-Medical Use of
BUT Only
a Small Proportion
Prescription
Opioids, of NonMedical Users
Progress to Heroin

National General Population:

Within 5 years, 3.6% of non-medical users of opioids

progressed to heroin within 5 years (i.e. less than
1% per year) (Muhuri, Gfroerer, Davies. 2013)

Local Longitudinal Study of Non-medical

users:

Within 3 years, 7.5% progressed to heroin (i.e. 2.8%

per year). (Carlson, Nahhas, martins, Daniulaityte. 2015)
Science =
Solutions

Heroin Market Has Changed:

Heroin Price Has Been Lower in Recent
Years
"Retail" Price Per Pure Gram

$3,500
$3,000
$2,500
$2,000
$1,500
$1,000
$500
$Source: National Drug Control Strategy--Data Supplement 2014.
https://www.whitehouse.gov/sites/default/files/ondcp/policy-and-research/ndcs_data_supplement_2014.pdf

Fentanyl: A Particularly
Potent Opioid
Jan. June 2009

Jan. June 2014

Reports per
State
100 or More
5099
2049
119
0
No Data

35 States reported
In the first half of 2014, 46
analyzing fentanyl
States reported fentanyl,
during the first half of
including 6 with 100 or
2009. No States had
more reports and 5 States
more than 49 fentanyl
between 50 and 99.
reports.Most
Two States
numbers
mainly in
overdosesHighest
are from
nonhad between 20 and 49
Midwest and Northeast.

pharmaceutical fentanyl (i.e. illicit

Secretary Burwells/HHS Opioid Priority

Areas

Opioid prescribing practices to

prevent opioid use disorders and
overdose

The expanded use of naloxone, used

to treat opioid overdoses

Expanded use of medication assisted

treatment (MAT) for opioid use
disorders

http://aspe.hhs.gov/sp/reports/2015/OpioidInitiative/es_OpioidInitiative.pd
f

Prevention: Risk for Young Adult Non-

Medical Use of Prescription Opioids

Predicted by Early Behavior
In MTF (Monitoring the Future) Follow up Study, 12 th
Grade Predictors of Young Adult Non-medical Use of
Prescription Opioids (all p < .05):
FACTOR

RELATIVE RISK

Lifetime MJ (at least 6 times use):

Lifetime Cigarettes (any):
Lifetime Rx Opioid Misuse (any):

2.21-2.92

1.56-2.08
1.97-5.88

Lifetime Sedative (1-5, 10-39 times):

Racial/ethnic Minority:

0.62

College Educated Parents:

1.23

1.63-2.93

Medical
UseL,of
Rx Opioid:
Source:
Miech R, Johnston
OMalley
PM, Keyes KM, Heard K. 1.33
Pediatrics 2013;136:e1169
Science =
Solutions

Prevention: Universal Drug Abuse

Prevention Reduces Prescription Drug

Misuse
16%

15.5%

13.5%

Control

12%
8%

5.4%

4.7%

4%
**

0%

**

In this study, for 100

young adults in
general population
starting Rx abuse,
only 35 young adults
from an intervention
community started.

Overall, three studies

-4%
now suggest the
impact of universal
prevention on
**
prescription drug
p<.01;
Notes: General=Misuse of narcotics or CNS depressants or stimulants.
abuse.
Source: R Spoth et al. American Journal of Public Health 2013

Science =
Solutions

in Striatum (nCi/cc)

Prevention: Less Abusable

Medications

0.0035
0.003
0.0025
0.002
0.0015

Slow
!!

Uptake

0.001
0.0005
00 20 40 60 80 100120

Time (minutes)

Develop medications with

lower abuse potential
including drugs that dont
cross the Blood-BrainBarrier (i.e., CbR2 agonist)
Develop slow release
formulations (low dose and
long duration) and prodrug
formulations (only
activated with digestion)
Develop novel formulations
to reduce abuse liability
including mixture
Science =
formulations (e.g., Solutions

Prevention: Reformulation of extendedrelease oxycodone reduced its abuse

among persons in rural Kentucky who
abuse prescription opioids
A
A study
study conducted
conducted in
in Perry
Perry
County,
County, Kentucky
Kentucky
demonstrated
demonstrated that
that the
the
introduction
introduction of
of
reformulated
reformulated extendedextendedrelease
release oxycodone
oxycodone (ERO),
(ERO),
which
which was
was designed
designed to
to be
be
more
more difficult
difficult to
to take
take nonnonmedically,
medically, caused
caused a
a
decrease
decrease in
in non-medical
non-medical
use
use of
of ERO,
ERO, especially
especially by
by
snorting
snorting and
and injection.
injection. The
The
reformulation
reformulation was
was
introduced
introduced between
between August
August
and
and December
December 2010.
2010.
Havens,
Havens, J.R.,
J.R., Leukefeld,
Leukefeld, C.G.,
C.G., DeVeaugh-Geiss,
DeVeaugh-Geiss, A.M.,
A.M.,
Coplan,
Coplan, P.,
P., Chilcoat,
Chilcoat, H.D.,
H.D., 2014.
2014. The
The impact
impact of
of aa
reformulation
reformulation of
of extended-release
extended-release oxycodone
oxycodone designed
designed
to
to deter
deter abuse
abuse in
in aa sample
sample of
of prescription
prescription opioid
opioid
abusers.
abusers. Drug
Drug and
and Alcohol
Alcohol Dependence
Dependence 139,
139, 917.
917.
doi:10.1016/j.drugalcdep.2014.02.018
doi:10.1016/j.drugalcdep.2014.02.018

Prevalence of abuse of original ERoxycodone(ERO), reformulated ERO, any ERO, and IR

oxycodone based on current recall (December 2010 through September 2011) and
retrospective recall (August 2010). Pre-reformulation (August 2010):n=189. Postreformulation: December 2010February 2011:n=51; March 2011April 2011:n=64;
May 2011June 2011:n=43; July 2011September 2011,n=31. Error bars are 95%
Confidence Intervals (CI). Dotted horizontal lines represent the mean values for each
drug.

Science =
Solutions

Prevention: Non-Medication
Treatments for Pain and
Addiction
Left periventricular grayLeft sensory thalamus

Transcranial
Magnetic
Stimulation
(TMS)
Deep Brain Stimulation (DBS)
Stereotaxtic implantation of
electrodes that emit electrical
stimulation to a targeted
neuronal region

Gray AM et al., J Pain 2014; 15(3): 283292.

High-Definition transcranial
Direct Current Stimulation (HD-tDCS)
Transcranial Direct
Current Simulation
(tDCS)
Science =
ena-Duarte I et al., Neuroimage 2014; 85(3): 1003-1013.
Solutions

Direct Overdose Intervention

Naloxone Distribution for opioid
overdose victims. The potential for
direct intervention to save lives.
Note the April 3, 2014 FDA
approval of the naloxone
auto-injector (called
Evzio)

Naloxone Nasal Spray Development

Needle-free, unit-dose, readyto-use

opioid overdose antidote.
Adapt Pharma NARCAN nasal
spray APPROVED BYScience
FDA, =
November 18, 2015.Solutions

Retail Pharmacy Prescriptions for

Naloxone Increase Markedly
Retail prescriptions
show an increase of
1170% from the 4th
quarter of 2013 to 2nd
quarter 2015.
Outpatient prescribing
of naloxone may
complement
community-based
distribution and first
responder access.

201
5

Evzio
Naloxone
Other
2mg/2ml
201
4

Jones CM, Lurie PG, Compton WM. American Journal of Public Health. February
18, 2016.
Science
=

Solutions

Mu Opiate Receptor Stimulating

Drugs (e.g. Heroin, Vicodin,
Morphine) Increase Dopamine
Release in Nucleus Accumbens
(Nac)
Mu opiate receptors
in Nucleus
Accumbens (Nac)
Opiates
Opiates

Nestler, Nature
Neurosci, 2005

Science =

Medications for Opioid Addiction

Full Agonist: Methadone (daily dosing)

Partial Agonist: Buprenorphine (3-4X week)
Antagonists: Naltrexone (ER 1 month)
antagonist

agonist

OpioidEffect

FullAgonist
(Methadone)

noeffect

effect

Bindstoreceptorbuthas
noeffect.
Preventsheroinfrom
binding

Bindstothereceptorandactivatesit;
Fullagonistshavemaximaleffect
Partialagonisthaveintermediateeffect
PreventHeroinfrombinding

PartialAgonist
(Buprenorphine)

Antagonist
(Naltrexone)

LogDose

Science =
Solutions

Accessing Medications Can Save Lives

Opioid Agonist Treatments Decreased Heroin
Baltimore,
1995-2009
ODMaryland,
Deaths

Heroin overdoses
Buprenorphine patients
Methadone patients

Schwartz RP et al., Am J Public Health

2013.

Science =
Solutions

Improving Treatments for Addiction:

Extended Release Buprenorphine to Improve Compliance

Implanted
buprenorphine may
improve compliance
Trial: buprenorphine
implants
vs. placebo for 6
months

Probuphine

Rosenthal et al., Addiction

2013;105.

Rosenthal RN et al., Addiction 2013;105:2141-21

Improving Treatments for Addiction:

Extended Release Naltrexone in Criminal Justice
Involved Populations

Participants: parolees/probationers with opioid

addiction all volunteers received either

Probability of No Relapse

Monthly injections of extended release naltrexone for 6

months
Community treatment, including methadone or
Suboxone (encouraged)
Relapse Frequency

Naltrexone
Treatment as usual

Overdoses in 78
weeks:
Control: 7
Naltrexone: 0
Lee et al. NEJM March 31, 2016.

Science =

Weeks
OBrien et al., Poster presentation
at the Annual Meeting of the College on Problems of
Drug Dependence, June 2015.

ADDICTION: Immunotherapies

(Vaccines)

Antibodies (i.e. Vaccines) reduce amount of drug in the

brain
Vaccin
e
Antibodies

Capilla
ry
Blood
Flow

Brain

Targets
drugs,
not
receptors

Binding
sites

Capilla
ry
Blood
Flow

Brain

Science =
Solutions

Additional Challenge

Lack of of medication-assisted treatment

capacity

Rate of Opioid
Abuse/Dependence

3.4-6.4
6.5-9.2
9.4-10.3
10.8-12.9
Rate of OA-MAT
Capacity

0.7-3.0

(rate per 1,000 persons aged 12 years and older)

CM, Campopiano M, Baldwin G, McCance-Katz E. National and state treatment need and capacity for opioid agonist medication assisted treatment. AJPH. 2015

3.2-4.3
4.4-7.2
7.3-16.5

% engaged in treatment on the

30th day after randomization

Implementation: Access to Buprenorphine

in Emergency Department Increased
Engagement
In Addiction
Treatment
Trea & Reduced
Self-reported
Illicit Opioid
Use
90
80
70
60
50
40
30
20
10
0

78

5.6

5.4

37

45

2.3

DOnofrio, et al. JAMA. 2015.

Science =
Solutions

5.
4

2.4

0.
9

Number of days of illicit opiate use per week

Implementation: Medications May

Improve Health and Criminal Justice
Outcomes in Prisoner Rentry
Methadone Experiment: 6 Mo Post Release (N=201)
Community-based Tx days

% Opioid Test Positive

Crime Days

100
80
60
40
20
0
Release Referral to Methadone
Methadone
Treatment
TreatmentMethadone
on Releaseboth Pre- & Post-Release
-- signif. diff from referral
-- signif. diff from treatment only on release
Source: Gordon, M.S., Kinlock, T.W., Schwartz, R.P., OGrady, K.E. (2008). Addiction. A Randomized Clinical Trial of
Methadone Maintenance for Prisoners: Findings at 6-Months Post-Release.

Science =
Solutions

Implementation: Methadone
Discontinuation During Incarceration
Associated with Less Treatment
Continuity After Prison/Jail Release
Continued
During
Incarceration

Discontinued
During
Incarceration

Continuation of methadone maintenance during incarceration

as compared to forced withdrawal increased the likelihood of
re-engaging in methadone treatment (combined US prison and
jail,
randomized,
trial)
Rich
et al., The Lancetopen-label
Published online
May
29, 2015.

Science =

ummary: Science =
olutions

PREVENTION: Develop Less

Abusable Analgesics and

Alternative Therapeutics;
Overdose treatment; Universal
prevention
ADDICTION: New Medications
and Immunotherapies
PHARMACOGENOMICS:
Precision Medicine
IMPLEMENTATION SCIENCE:
Greater Use of Evidence

Science =

Science =
www.drugabuse Solutions
.gov