Drug Abuse & Addiction Research: Progress, Priorities, & Challenges

Transcription

1 Drug Abuse & Addiction Research: Progress, Priorities, & Challenges 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.

2 Office of Diversity & Health Disparities Office of Translational Initiatives and Program Innovations NIDA Office of the Director AIDS Research Program International Program Dr. Redonna Chandler Office of Management Office of Science Policy & Communications Intramural Research Program Division of Extramural Research Center for the Clinical Trials Network Division of Therapeutics and Medical Consequences Division of Neuroscience and Behavior Division of Epidemiology, Services and Prevention Research Kurt Rasmussen, Ph.D., Director, DTMC Formerly: Senior Research Advisor, Neuroscience Division, Eli Lilly & Co.

3 NIDA BUDGET (Thousands) FY 2017 Actuals FY 2018 Operating Plan FY 2018 Opioid Funding 1 FY 2019 President s Budget NonAIDS $794,102 $858,106 $250,000 AIDS $276,711 $268,551 TOTAL $1,070,813 $1,126,657 $250,000 $1,137,403 1 FY 2018 Opioid Funding expires September 30, 2019

4 Past Month Marijuana Use Remains Steady while Alcohol and Cigarette Use Declining among High School Seniors Alcohol Cannabis Cigarettes Marijuana-12th Cigarettes-12th E-Cigs-12th Alcohol-12th 17 SOURCE: University of Michigan, 2017 Monitoring the Future Study

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6 CANNABIS LAWS IN THE U.S. As of Jan. 22, 2018, the Vermont legislature passed adult-use legalization legislation and the governor signed the bill. The measure does NOT set up a regulatory system for sales or production. 29 states have legalized medical marijuana along with D.C., Guam and Puerto Rico States with MML vary on: Allowable conditions and routes of administration. Dispensaries/home growth and registries. Testing, regulatory requirements. States with Recreational Laws vary on: Marketing, product labeling, distribution (home growth). Taxation.

7 Construct a standardized dose Standards for measuring intoxication and impairment Determine dose under which functional impairment does not occur Epidemiology and trends for cannabis use and CUD Develop effective roadside tests for cannabis impairment that can be practically deployed by law enforcement. Determine prevalence of cannabis-involved crashes, other types of injury or property damage. Effects of different patterns of cannabis use on brain development, educational attainment, grades, test scores, high school completion, and transition to work Effects of maternal cannabis consumption during pregnancy and breastfeeding. Research on neurological, cognitive, and physical health impacts Research on the cannabis industry, including research on taxes and prices Research on the effects of alternative business models for retail distribution of cannabis Research on alternative regulatory models for public health and public safety Develop effective prevention and treatment strategies

8 ABCD Progress Number of Participants 9/1/ /1/2016 1/1/2017 ABCD Enrollment As of May 29, /1/2017 5/1/2017 7/1/2017 9/1/ /1/2017 1/1/2018 3/1/2018 Singletons Twins Total Target /1/2018 ABCD Study Fast Track Data DICOM images from ~6,000 participants currently available. Interim curated data on first ~4,500 participants released Feb 2018! Assessments of: o o o o Physical and mental health, Substance use, Culture and environment, and Neurocognition Tabulated structural and functional neuroimaging data Minimally processed brain images Biological data (e.g., pubertal hormone analyses) Residential history derived data related to residential density/walkability, crime, area deprivation, population density, and satellite-based pollution measures

9 New NIDA FOAs Workshop on the Use of Adolescent Brain Cognitive Development (ABCD) Data (R25 Clinical Trial Not Allowed) (RFA-DA ) Issued: March 28, 2018; Application Receipt/Submission Date(s): July 25, FOA will support creative educational activities with a primary focus on courses for skills development that will allow participants to explore the hands-on use of ABCD data, through cooperative or competitive approaches.

10 Overdose Death Rates Source:

11 Evolution of the Opioid Crisis Overdose Fatalities 1. Over prescription of opioid medications led to misuse 2. Addiction to prescription opioids led to heroin 3. Emergence of fentanyl(s), with higher potency and greater profitability in the black market than heroin.

12 NIH OPIOID RESEARCH INITIATIVE Using Research to End the Opioid Crisis PREVENTION OUD PAIN MANAGEMENT Safe, more effective strategies OPIOID ADDICTION TREATMENT New and innovative medications and technologies OVERDOSE REVERSAL Interventions to reduce mortality and link to treatment

13 Ligand-specific Spatiotemporal Distinctions in Opioid Receptor Signaling mor-gal 1 R heteromers in the VTA Stober M et al., Neuron Moreno et al, 2017, J Neurosci

14 Medication Assisted Treatment (MAT) OUD Cascade of Care in USA Opioid Effect Log Dose Full Agonist (Methadone: Daily Dosing) Partial Agonist (Buprenorphine: 3-4X week) Antagonist (Naltrexone: ER 1 month) DECREASES: Opioid use Opioid-related overdose deaths Criminal activity Infectious disease transmission INCREASES Social functioning Retention in treatment Williams AR, Nunes E, Olfson M. Health Affairs Blog, 2017 MAT is highly underutilized! Relapse rates are very high (50% in 6 months)

15 Collaborative Care for Opioid and Alcohol Use Disorders in Primary Care (FQHC) Percent Participant Outcomes at 6-Month Follow-up Abstinence opioids or alcohol past month In primary care, collaborative care intervention increased abstinence from alcohol and drugs compared to usual care. Treatment for OAUDs can be integrated into primary care settings. CC Usual Care Abstinence from any drug past month Overdose Deaths After Implementing OMT in Rhode Island Statewide Correctional System Number OD Fatalities Statewide Overdose Deaths /1 to 6/ % decrease 157 1/1 to 6/ OD fatalities in those who had been incarcerated in 2017 decreased by 60% compared to 2016 (5.7% vs 14.5%) Watkins KE et al., JAMA Intern Med. 2017;177(10): Green TC and Clarke J. JAMA Psychiatry 2018;75(4).

16 Percentage of subjects SUBLOCADE (Buprenorphine ER), Once-Month Injectable FDA Approval % urine samples negative for opioids (Weeks 5 to 24) RBP /100 mg + IDC RBP /300 mg + IDC * * CAM2038: Subcutaneous ER Buprenorphine Weekly or monthly injection Comparison CAM2038 versus Daily SL BPN % Participants p= >% Abstinence (opioid-free weeks) 0 % Negative Urine 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Heidbreder et al., CPDD 2017

17 Medication to Treat Opioid Withdrawal May the FDA approved lofexidine, the first medication targeted specifically to treat the physical symptoms associated with opioid withdrawal NIDA s medications development program helped fund the science leading to the drug s approval Courtesy of US WorldMeds, LLC US WorldMeds acquired a license for lofexidine from Britannia Pharmaceuticals in 2003 and will market it in the US under the brand name LUCEMYRA TM beginning this summer

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19 New NIH Initiative to Address the Crisis: HEAL: Helping to End Addiction Long-term Collaborative, cross-cutting research From basic to behavioral and everything between Innovative partnerships across agencies, sectors, organizations will ensure rapid progress $500M/year provided by Congress in FY18 Omnibus Advances national priorities for pain and addiction research Collins, Koroshetz, Volkow JAMA 2018

20 NIH HEAL Initiative: Selected Priorities for 2018 Opioid Use Disorder Improve therapeutic approaches to addiction and overdose Carry out real world implementation research to optimize interventions Evaluate treatments, consequences of Neonatal Opioid Withdrawal Syndrome (NOWS) Pain Management Understand neurobiology of chronic pain Develop new non-addictive treatments for pain Build Clinical Trial Network for chronic pain

21 NIDA Projects Selected by NIH for 2018 Funding 1. Focused Medications Development -- $70,250, CTN Expansion -- $29,000, Justice Community Opioid Intervention Network -- $5,750, Multisite Implementation Research Study --

22 New Treatments for Addiction, Overdose Prevention and Reversal New ER formulations of existing medications to treat OUD Stronger, longer-acting opioid antagonists to counteract overdose Interventions against respiratory depression other than MOR antagonists Novel medications (new targets) to treat withdrawal, craving, progression, overdose prevention and relapse Immunotherapies Projected Impact: 15 Investigational New Drug (IND) applications 5 New Drug Applications (NDAs)

23 Enhanced Clinical Trials Network Expand the size and scope of the CTN Expand clinical research of CTN with ED and primary health care Develop and validate new models of OUD care Develop and validate new metrics for evaluation Contribute to improved quality of and access to treatment for OUD In general medical and specialty settings In rural communities Expand clinical research workforce in OUD screening and treatment Determine criteria to indicate inpatient vs outpatient treatment Collect longer-term outcomes for different tx settings and modalities Treatment interventions for mild OUD or subclinical opioid misuse Research to address cost and sustainability

24 Justice Community Opioid Innovation Network Increase collaborations between justice systems and community-based treatment providers to improve continuity of care Enhance access and retention in OUD treatment Justice community-related research through network of investigators National survey of addiction treatments in jails, prisons and communities Effectiveness and implementation studies of new and existing medications, interventions, and technologies in justice settings Leveraging existing data sources Developing innovative research methods

25 Multisite Implementation Research Study Can we draw on all we know now and develop integrated evidenced based intervention strategies to stem the crisis quickly? Study ways to integrate evidence-based interventions comprehensively in areas highly affected by the crisis Involve federal, state, local partnerships, integrating ALL stakeholders Health care (ED and primary care), justice, treatment programs, government agencies, first responders Prevent OUD and OD Screen and diagnose Engage and retain in medication-assisted treatment Help sustain long-term recovery Opioid Use Disorder Cascade of Care

26 America's startups and small businesses create technologies to ease the opioid epidemics RFA $8-9 million total for 3 years New initiative open to eligible for profit small businesses R43/44 mechanism Matching fund requirement New tools and technologies to stop the opioid crisis and prevent future ones Special emphasis on overdose prevention and reversal Questions NIDASBIR@mail.nih.gov

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28 Drug Poisoning Deaths 2016 All Ages in Poverty Source: CDC NCHS, census.gov

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30 Additional Research Priorities Prevention (beyond improving prescriptions practices for pain) Precision treatments for addiction Non-pharmacological treatments Integrated models of pain management Linkages between pain, addiction, mental health Education