Nora D. Volkow, M.D.Director

Heroin Addiction and Overdose:What Can We Do to Address This Growing Problem?

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

Illicit Drugs4.7

4.95.1 5

4.8 4.9 4.8

4.3

4.8

4.2

2.1 2.2 2.1 2.1 22.2 2.2

22.3

2

1.2 1.11.4

1.2 1.1 1.2 1.1 11.3 1.3

0.3 0.3 0.4 0.3 0.2 0.3 0.40.2 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+

Perc

ent

Past Year Nonmedical Use of Psychotherapeutic Drugs

Persons Ages 12+

High Levels of Opioid Prescriptions have Facilitated Diversion & Contributed to Overdose Deaths

4,0304,400

5,528

7,456

8,517

9,857

10,928

13,72314,408

14,80015,597

16,65116,91716,00716,235

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 & Hydrocodone Prescriptions

16 19 22 25 27 29 31 34 3843 47 49

54 57 57

7283

9096

101106 110

120126

132 133 130 131136 134

0

20

40

60

80

100

120

140

160

Mill

ions

Oxycodone (Schedule II)Hydrocodone (Schedule III)

SDI Health, VONA_02-1-13_Opioids Schedule II & III

Past Month &Past Year Heroin Use Persons Aged 12 or Older

SAMHSA, 2012 National Survey on Drug Use and Health, 2014.

404

314

398379

560

373

455

582621 620

669 681

166

119

166136

339

161

213193

239281

335

289

0

100

200

300

400

500

600

700

800

2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Past Year

Past Month

Num

bers

in T

hous

ands

1,960 1,842 1,7792,089 2,080

1,878 2,009 2,0882,399

3,0413,278

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

Respondents Who Endorsed Past-MonthUse of OxyContin or Heroin

Before and After Introduction ofan Abuse-Deterrent Formulation (ADF)

Drugs Used to Replace OxyContin After the Introduction

of the Abuse-Deterrent Formulation (ADF)

60

50

40

30

20

10

0

Past

-Mon

th A

buse

Am

ong

SKIP

Res

pond

ents

, %

Jan-Jun2009

Jul-Dec Jan-Jun2010

Jul-Dec Jan-Jun2011

Jul-Dec Jan-Jun2012

Jul-Dec Jan-Jun2013

Jul-Dec Jan-Jun2014

ADF Release Heroin

OxyContin

RA

PID

Res

pond

ents

, %

80

70

60

50

40

30

20

10

0

Drug Selected to Replace OxyContin

Cicero TJ and Ellis MS JAMA Psychiatry. Published Online March 11, 2015.

Analgesic Mechanisms of Mu Opiate Drugs (Heroin, Vicodin, Morphine)

Thalamus(pain)

ACC(pain) PAG

(pain)

Accumbens(reward)

How Can Research Help?

• PAIN: Develop Less Abusable Analgesicsand Alternative Therapeutics

• OVERDOSES: User Friendly Naloxone

• ADDICTION: New Medications and Immunotherapies

• Pharmacogenomics (Precision Medicine)

• Implementation Science

Develop Less Abusable Drugs:Prodrugs

• Problem: changing method of taking opioids – i.e., crushing, injecting – increases euphoria; abuse

• Challenge: develop drugs that resist tampering; abuse

• Research response: oxycodone prodrug– Inactive compounds metabolized in the body to

produce active drug

Transcranial Direct Current Simulation (tDCS)

High-Definition transcranialDirect Current Stimulation (HD-tDCS)

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)

PAIN: Alternative Therapeutics

Improving OD Treatments:Naloxone for Overdose

• Lay-friendly administration: intranasal naloxone

• AntiOp, developing disposable naloxone nasal spray. Product could be on the market 2015

• Lightlake Therapeutics, conducting clinical trials with intranasal naloxone for binge eating disorder will test this for opioid overdose

Improving Implementation of Medication Assisted Treatments: Addiction

25%

9%17%

9%16% 19%

0%10%20%30%40%50%60%70%80%90%

100%

% Treatment Programs Offering FDA-approved SUD

medications

Methadone26.4%

Buprenorphine3.9%

Vivitrol0.3%

Not receiving Methadone,

Buprenorphine or Vivitrol

69.4%

% OTP patients receiving methadone, buprenorphine,

or vivitrol

Knudsen et al., J Addict Med 2011. 2012 N-SSATS Data, SAMHSA

Opioid Agonist Treatments Decreased Heroin OD Deaths

Baltimore, Maryland, 1995-2009

Heroin overdoses Buprenorphine patientsMethadone patients

Rosenthal RN et al., Addiction 2013;105: 2141-2149.

Buprenorphine Implants

Placebo

Sublingual Buprenorphine

Challenge: Compliance with daily intakeSolution: develop long acting medications

Schwartz RP et al., Am J Public Health 2013.

ADDICTION: New Medications & ImmunotherapiesRCT Buprenorphine Implants

vs Placebo & Sublingual Buprenorphine/Naloxone

…………………….........Probuphine is designed to release sustained therapeutic drug levels in patients with opioid addiction for up to six months

% o

f Pat

ient

s Fai

ling

to E

xcee

d E

ach

Poss

ible

Cri

teri

on o

f Suc

cess

% of Urines Negative (out of 72) for Opioids Across Weeks 1 to 24

Antibodies reduce amount of drug in the brain

CapillaryBlood Flow

Brain

Treating Opioid Addiction: Vaccines

Targets drugs, not receptors

CapillaryBlood Flow

Brain

Antibodies

Vaccine

Binding sites

• Responsible Prescribing and Managementof 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

Implementation Science

National Pain Strategy

”HHS Secretary should develop a comprehensive, population health-level strategy for pain prevention, treatment, management, education, reimbursementand research ..."

NIH Pain ConsortiumCenters of Excellencein Pain Education

Goal: Improve pain treatment through education

• 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

Walley AY et al., BMJ 2013; Published 31 January 2013.

Opioid Overdose Death Rates Were ReducedIn Communities Where Overdose Education & Nasal

Naloxone Distribution Program (OEND) Was Implemented Unadjusted Unintentional

Opioid-Related Overdose Death Rates

Unadjusted Opioid-Related Acute Care Hospital Utilization Rates

Which Drug is the First Opioid Used in Addicts? Shifting Pattern of Heroin vs. Rx Opioid First

Percentage of Heroin-Addicted Treatment Admissions that Used Heroin or Prescription Opioid as First Opioid

Source: Cicero et al. JAMA Psychiatry. 2014;71(7):821-826

1960s: more than 80%started with heroin

2000s: 75% started with prescription opioids

2010-2013: Increasing initiation with heroin

100

90

80

70

60

50

40

30

20

10

01960s 1970s 1980s 1990s 2000s 2010s

(n=88) (n=114) (n=214) (n=482) (n=1613) (n=286)Decade of First Opioid Use (No. of Abusers)

Tota

l Sam

ple,

%

` Prescription OpioidHeroin

`

``

`

`

`

Age-Adjusted Rates for Drug-Poisoning Deaths Involving

Heroin, By Census Region: US

CDC, NCHS Data Brief, No 190, March 2015.

Dea

ths p

er 1

00,0

00 p

opul

atio

n

Northeast Midwest South West

5

4

3

2

1

0

20002007 2013

Northeast

Rates for Drug-Poisoning DeathsInvolving Heroin, By SelectedAge & Race & Ethnicity Groups

Dea

ths p

er 1

00,0

00 p

opul

atio

n

20002013

8

7

6

5

4

3

2

1

0 18-44 45-64 18-44 45-64 18-44 45-64

Non-HispanicWhite

Non-HispanicBlack

Hispanic

CDC, NCHS Data Brief, No 190, March 2015.

Possible Consequences of Heroin UseIncreased Risk of Contracting Infectious Diseases including:HIV/AIDSHepatitis B and C

Incidence of acute hepatitis Cby age group, U.S., 2000-2011

0

0.5

1

1.5

2

2.5

3

Rep

orte

d ca

ses/

100,

000

popu

latio

n

0–19 yrs

20–29 yrs

30–39 yrs

40–49 yrs

50–59 yrs

≥60 yrs

Source: National Notifiable Diseases Surveillance System (NNDSS), CDC