Dr. Francis Collins, Director of the National Institutes of Health, keynote address at the National Rx Drug Abuse & Heroin Summit on March 29, 2016.

1. Opioid Drug Abuse: NIH Research
Francis S. Collins, M.D., Ph.D.
Director, National Institutes of Health
5th Annual National Rx Drug Abuse and Heroin Summit
March 29, 2016

2. NIH: Steward of Medical and Behavioral
Research for the Nation
“Science in pursuit of fundamental
knowledge about the nature and
behavior of living systems
and the application of that knowledge
to extend healthy life and reduce
illness and disability.”
...

3. NIH Funds Scientists Across The U.S.

4. NIH Research: Opioid Drug Abuse
 Pursuing fundamental knowledge of pain
 Developing alternatives for pain management
 Limiting abuse of opioids
– Enhancing safety
– Predicting addiction
– Improving treatments for addiction and overdose

5. Knowledge of Pain Pathways –
New Biomarkers for Pain?
New study to determine role of glial cells in pain
 Pairs patients with low back pain (LBP) and
healthy controls
– Uses imaging to detect levels of specific glial protein
– Paradoxically, higher levels = less subjective pain
 Demonstrates role of glial activation in human pain
– Possible biomarker
– May suggest new treatments for chronic pain
Loggia et al., Brain 2015;138.

6. NIH Research: NIH Pain Consortium
NIH-wide effort to enhance pain research, including:
 Centers of Excellence in Pain Education (CoEPEs)
 Task Force on Research Standards for Chronic Low Back Pain
 Pathways to Prevention: Efficacy of Opioids for Chronic Pain
 NIH Blueprint for Neuroscience Research’s Grand Challenge on the
Transition from Acute to Chronic Neuropathic Pain RFA

7.  2011: Institute of Medicine calls for coordinated approach
to relieving burden of pain in U.S.
– Tasked Health & Human Services to develop plan
 2012: HHS created the Interagency Pain Research
Coordinating Committee (IPRCC)
 IPRCC: chaired by NIH, brought together nearly 80
experts from public and private sectors
– Received public comment on draft Strategy
 March 2016: National Pain Strategy released
NIH Research: A National Strategy for
Reducing Pain
Department of Health and Human Services

8. Public
Education &
Communication
Disparities
Care &
Prevention
y
nt
Focuses on Six Key Areas
Major Objectives:
 Develop methods to improve pain prevention, management
 Devise system of patient-centered integrated pain management
practices
 Reduce barriers to, improve quality of, pain care - particularly for
vulnerable or underserved populations
 Increase awareness of pain, care options - for public, patients,
health care workforce

9. NIH Research: Opioid Drug Abuse
 Pursuing fundamental knowledge of pain
 Developing alternatives for pain management
 Limiting abuse of opioids
– Enhancing safety
– Predicting addiction
– Improving treatments for addiction and overdose

10.  Transcranial Magnetic Stimulation shown to
diminish pain of
– Headaches related to mild traumatic brain injury
– Post-herpetic neuralgia
 Spinal Cord Stimulation indications include
– Painful diabetic neuropathy
– Chronic painful radiculopathy
 Acupuncture
– Meta-analysis suggests role for managing chronic pain
– Improvement with headache; musculoskeletal,
osteoarthritis pain
Developing Non-Medication Strategies
for Pain Management
Lamer et al., Mayo Clinic Proceedings 2016; 91.
Spinal Cord Stimulation
©Mayo 2015
Transcranial Magnetic
Stimulation
Leung et al., Pain Physician 2016;19.

11. Study of Rare Disease Points to
New Target for Pain Control
 Congenital analgesia: rare condition, individuals cannot feel pain
– Mutation identified in gene that encodes for Nav1.7 – sodium channel
that regulates pain-sensing neurons
 Targeting Nav1.7 to produce analgesia
– Several companies now have drugs in pipeline to block channel
 Targeting complications
– Understanding what happens when Nav1.7 is blocked
– NIH grantees developing new, more selective drugs to block Nav1.7

12. NIH Research: Opioid Drug Abuse
 Pursuing fundamental knowledge of pain
 Developing alternatives for pain management
 Limiting abuse of opioids
– Enhancing safety
– Predicting addiction
– Improving treatments for addiction and overdose

13. Limiting Abuse by Enhancing Safety
Opioid deterrent formulations
 Pro-drugs
 Tamper resistance
 Drug combinations with adverse effects if injected

14. Enhancing Safety: Prodrugs
 Problem: changing method of taking opioids – i.e., crushing, injecting –
increases euphoria and abuse
 Challenge: develop drugs that resist tampering
 Research response: oxycodone prodrug BIO-MD™
– Inactive compounds metabolized in the body to produce active drug
– Has broad potential across all known prescription opioid drugs
• Achieved human proof of concept with PF329, hydromorphone prodrug
• PF614 is lead abuse-resistant opioid drug program

15. Limiting Abuse by Predicting Addiction
 OPRM1 encodes for the target of
opioids – and varies from person to
person
– Can variants predict likelihood of
addiction?
 OPRM1 variant
– Affects specific receptor levels in brain
– Associated with increased risk for
addiction, overdose severity
Hancock et al., Biol Psychiatry 2015; 78.
Manini et al., J Med Toxicol 2013; 9.
Peciña et al., Neuropsychopharmacology 2015; 40.
Variant Common Type
Mapping the differences

16. Rosenthal et al., Addiction 2013;105.
Improving Treatments for Addiction:
Extended Release Medications Improve Compliance
 Buprenorphine: partial opioid agonist
– Has lower abuse potential
– Suppresses symptoms of
withdrawal
– Helps people stay in treatment
 Implanted buprenorphine may
improve compliance
– Trial: buprenorphine implants
vs. placebo for 6 months
EVA polymer Probuphine®Buprenorphine
+ =

17. 5.4 5.4 5.6
0.9
2.3 2.4
0
1
2
3
4
5
6
Buprenorphine Referral Brief Intervention
Baseline 30 days
Improving Treatments for Addiction:
Implementing Medication-Assisted Treatment
 Emergency department-initiated buprenorphine
– Reduced self-reported, illicit opioid use
– Increased engagement in addiction treatment; decreased use of
inpatient addiction treatment services
Days
Self-Reported Illicit Opioid Use in the Past 7 Days

18. Improving Treatments for
Pregnant Women Addicted to Opioids
 Methadone: recommended treatment for addiction in pregnant
women; however, prenatal exposure associated with neonatal
abstinence syndrome (NAS)
– Often requires extended hospitalization
– Incidence almost doubled in 4 years
 Buprenorphine: alternative treatment?
 Trial: offspring of mothers receiving buprenorphine compared to
methadone had:
– Shorter hospital stays (10 vs 17.5 days)
– Shorter duration of NAS (4.1 vs 9.9 days)

19. Using Research to Improve
Opioid Intervention Services
NIH is partnering with the Appalachian Regional Commission to fund
grants to address increased opioid injection drug use in the region
 One-year research planning grants to:
– Improve understanding problem’s 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-16-015.html

20. Improving Treatments for Addiction:
Naltrexone
 Naltrexone: opioid antagonist related to naloxone
 Extended release formula (Vivitrol) approved by FDA in 2006 for
alcohol dependence; approved for opioid addiction in 2010
– First non-narcotic, non-addictive extended release medicine for
treatment of opioid dependence
 Multiple NIH-supported
clinical trials now underway…

21. Overdoses in 78 weeks:
Control: 7
Naltrexone: 0
Improving Treatments for Addiction:
Naltrexone Trial Shows Promise
 Participants: parolees/probationers with opioid addiction – all
volunteers – received either
– Monthly injections of extended release naltrexone for 6 months
– Community treatment, including methadone or Suboxone (encouraged)
O’Brien et al., Poster presentation at the Annual Meeting of the College on Problems of Drug Dependence, June 2015.
Relapse Frequency
ProbabilityofNoRelapse
Weeks
Treatment as usual
Naltrexone

22.  Naloxone: medication that can halt an opioid overdose
– Original formulation delivered by injection
 Lay-friendly administration: intranasal naloxone
– NIH and FDA supported development
– Overdose education and naloxone distribution (OEND)
programs demonstrated to be effective
 NARCAN Nasal spray device
– $37.50 per 4mg
 Approved by FDA, November 2015
Improving Treatments for Overdose:
Naloxone
Image courtesy of
ADAPT Pharma, Inc.

23. Coming soon: the Precision Medicine Initiative®
An opportunity to advance research on common U.S.
medical problems – including opioids
www.nih.gov/precisionmedicine

24. “We lose almost a hundred Americans a
day from overdoses of prescription
medicine and heroin…. We need a
holistic, multipronged approach to the
epidemic.”
~Rep. Hal Rogers
Appropriations Hearing
March 16, 2016

25. NIH… Turning Discovery Into Health
directorsblog.nih.gov @NIHDirector