Director’s Report to the National Advisory Council

on Drug Abuse

September 4, 2013

Nora D. Volkow, M.D., Director

Director’s Report to the National Advisory Council on Drug Abuse

• Budget Update

• Recent NIDA Activities & Events

• What’s New @ HHS/NIH?

NIDA BUDGET (Thousands)

AIDS

TOTAL

NonAIDS

2012 Actuals

$733,076

$319,292

$1,052,368

2013 Operating Level

$691,816

$300,749

$992,565

2014 PB

$739,326

$332,286

$1,071,612

Director’s Report to the National Advisory Council on Drug Abuse

• Budget Update

• Recent NIDA Activities & Events

• What’s New @ HHS/NIH?

“The Next Great American Project”

Learning the Language of the Brain

BRAIN Initiative: Goals • Accelerate development, application of innovative technologies

to construct dynamic picture of brain function that integrates neuronal and circuit activity over time and space

• Build on growing scientific foundation – neuroscience, genetics, physics, engineering, informatics, nanoscience, chemistry, mathematics, etc. – to catalyze interdisciplinary effort of unprecedented scope

BRAIN Initiative: Partners FY2014 Investments

Government Agencies $ in Millions

National Institutes of Health $40

Defense Advanced Research Projects Agency $50

National Science Foundation $20

Private Organizations

Allen Institute for Brain Science $60

Howard Hughes Medical Institute $30

Salk Institute for Biological Studies $28

The Kavli Foundation $4

• Plan to be developed by NIH Advisory Council to the Director BRAIN Working Group - Selected for visionary leadership, expertise

- Charged with articulating scientific goals, developing plan

• Including timetables, milestones, costs

• NIH BRAIN Working Group will - Seek broad input; hold open meetings, workshops

- Deliver interim report on high-priority areas for FY14 funding in summer 2013; final report, June 2014

- Informed by experts across sectors and disciplines; assisted by NIH Blueprint for Neuroscience Research

NIH and BRAIN: How will it work?

Cornelia Bargmann, PhD (co-chair) The Rockefeller University

Bill Newsome, PhD (co-chair) Stanford University

David Anderson, PhD California Institute of Technology

Emery Brown, MD, PhD Massachusetts Institute of Technology

Karl Deisseroth, MD, PhD Stanford University

John Donoghue, PhD Brown University

Peter MacLeish, PhD Morehouse School of Medicine

Eve Marder, PhD Brandeis University

Richard Normann, PhD University of Utah

EX OFFICIO MEMBERS

Kathy Hudson, PhD National Institutes of Health

Geoffrey Ling, MD, PhD Defense Advanced Research Projects Agency

John Wingfield, PhD National Science Foundation

Joshua Sanes, PhD Harvard University

Mark Schnitzer, PhD Stanford University

Terry Sejnowski, PhD Salk Institute for Biological Studies

David Tank, PhD Princeton University

Roger Tsien, PhD University of California, San Diego

Kamil Ugurbil, PhD University of Minnesota

NIH and BRAIN: NIH Working Group

NIH BRAIN Working Group: Summer Schedule

DATE LOCATION FOCUS

May 29-30 San Francisco, CA Molecular Approaches

June 26-27 New York, NY Large-Scale Recording Technologies and Structural Neurobiology

July 29-30 Boston, MA Computation, Theory, and Big Data

August 29-30 Minneapolis, MN Human Neuroscience

September 16 ACD Teleconference ACD Vote on interim report on high-priority areas for FY14 funding

*Diversity of models and systems incorporated into each session

Features of the BRAIN Initiative

• Potential for wide-ranging benefits

– Dedicated to providing tools to enhance many areas of research

– Should provide methods for deeper understanding of all brain disorders

Impact on support for other research

NIH spends approximately $5.5B on neuroscience research; BRAIN Initiative is <1%

NIH Initiative to Enhance Reproducibility and Transparency of Research Findings

Courtesy of Dr. S. Silberberg, NINDS

• Lack of reproducibility of published research findings. • Underlying issues: –Poor education –Poor evaluation –Perverse reward incentives

Prinz, Schlange and Asadullah

Bayer HealthCare

Nature Reviews Drug Discovery 2011; 10:712-713

Almost 2/3 of 67 in-house projects

at NINDS could not replicate data

published by others

Problem

Hackam and Redelmeier, JAMA 2006; 14: 1731-1732

Journals: • Cell • Nature • Science • Nature Medicine • Nature Genetics • Nature Immunology • Nature Biotechnology >500 citations Translated to human studies

Deficient reporting is widespread

Courtesy of Dr. S. Silberberg, NINDS

• Ad-hoc group met to develop approaches. – Discussions informed by IC efforts (e.g., NCI, NINDS). • Group came to a consensus on guiding principles to address the underlying issues.

Principles for Addressing Issues

1. Raise community awareness.

2. Enhance formal training.

3. Improve the evaluation of applications.

4. Protect the integrity of science by adoption of more systematic

review processes.

5. Increase stability for investigators.

Addressing the Issues

Recommendations

1. Discuss with Advisory Councils and BSCs and hold workshops to the issue of reproducibility.

2. Integrate courses on experimental design into training courses.

3. Consider options for an evaluation process of a grant. 4. Adapt NIH bio-sketch to to place PI’s work into context. 5. Collaborate with scientific journals and scientific community on

efforts to improve rigor.

6. Consider the advisability and approach to supporting replication/reproducibility studies or centers

Elena Koustova will discuss further this afternoon…

NIH Transformative Research Awards (R01) RFA-RM-13-008

New Common Fund FOAs

NIH Director's New Innovator Award (DP2) RFA-RM-13-007

Due Date(s): October 25, 2013, October 17, 2014 & October 16, 2015.

Supports individual scientists or groups of scientists proposing groundbreaking, exceptionally innovative, original and/or unconventional research

Due Date: October 4, 2013.

Supports early stage investigators of exceptional creativity who propose bold and highly innovative new research approaches

NIH Pioneer Award Program (DP1) RFA-RM-13-006 Due Date(s): October 18, 2013, October 10, 2014 and October 9, 2015.

Supports individual scientists of exceptional creativity who propose pioneering & possibly transforming approaches

Due Date: January 31, 2014

NIH Director's Early Independence Awards (DP5) RFA-RM-13-009

Supports exceptional investigators who wish to pursue independent research directly after completion of their terminal doctoral/research degree or clinical residency

Collaborative Research on Addiction at NIH (CRAN)

Susan Weiss will be presenting an update this afternoon…

Recent Functional Integration FOAs

Revision Applications to Promote Collaborative Research on Addiction at NIH (CRAN): Comorbidity-Related Research

(R01) RFA-DA-14-014. Issued: July 15, 2013; Open Date: August 24, 2013; App. Due Date: September 24, 2013.

Administrative Supplements to Promote Collaborative Research on Addiction at NIH (CRAN): Comorbidity-

Related Research (Admin Supp) PA-13-275

Funds are available for revisions to augment existing R01 to help meet the goals of Collaborative Research on Addiction at NIH (CRAN)

Issued: July 15, 2013; Open Date: August 24, 2013; App. Due Date: September 24, 2013.

Funds are available for administrative supplements to parent awards in order to help meet the goals of CRAN; namely, the support of research in cross-cutting areas of SUD and related health consequences.

Director’s Report to the National Advisory Council on Drug Abuse

• Budget Update

• Recent NIDA Activities & Events

• What’s New @ HHS/NIH?

Results from the 2012 National Survey on Drug Use and Health

68,309 respondents in 2012

Past Month Use of Selected Illicit Drugs among

Persons Aged 12 or Older: 2002-2012

+ Difference between this estimate and the 2012 estimate is statistically significant at the .05 level.

8.3+ 8.2+

7.9+ 8.1+ 8.3+ 8.0+ 8.1+

8.7 8.9 8.7 9.2

6.2+ 6.2+ 6.1+ 6.0+ 6.0+ 5.8+ 6.1+

6.7+ 6.9 7.0 7.3

2.7 2.7 2.5 2.7 2.9 2.8 2.5

2.8 2.7 2.4 2.6

0.9+ 1.0+ 0.8+ 1.0+ 1.0+ 0.8+ 0.7 0.7 0.6 0.5 0.6

0.5 0.4 0.4 0.4 0.4 0.4 0.4 0.5 0.5 0.4 0.4 0

2

4

6

8

10

2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012

Illicit Drugs

Marijuana

Cocaine Hallucinogens

Psycho-therapeutics

Percent Using in Past Month

Daily or Almost Daily Marijuana Use in the Past

Year and Past Month among Persons Aged 12 or

Older: 2002-2012

+ Difference between this estimate and the 2012 estimate is statistically significant at the .05 level.

3.1+ 3.1+ 3.2+ 3.4+

3.1+

3.6+ 3.9+

4.1+

4.6+ 5.0

5.4

4.8+ 4.9+ 4.9+ 5.1+ 5.1+ 5.1+

5.5+

6.2+

6.9 7.1

7.6

0

1

2

3

4

5

6

7

8

2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012

Used Marijuana on 20

or More Days in the

Past Month

Used Marijuana on

300 or More Days in

the Past Year

Numbers in Millions

Changes in Marijuana Policy in the USA

Cerda M et al. Drug and Alcohol Dependence 2012; 120: 22 – 27.

NESARC: National Epidemiologic Survey on Alcohol and Related Conditions

1.81 1.92

1.03

0

0.5

1

1.5

2

2.5

Past Year MJ Abuse/Dependence Past Year MJ Use Past Year MJ Abuse/Dependence

Among Current Users

Map Of States That Legalized Marijuana By 2004

passed laws legalizing MJ

Od

ds

Rati

o

Outcomes of Interest

As of now 20 states in the USA

have approved the legalization

of medical marijuana

Availability of supplements to inform social, behavioral, and public health impacts of recent US marijuana legalization policies.

Research on Marijuana

Legalization in the US

(Admin Supp) P A-13-138

Open date(s): April 30, 2013.

Application due date(s): May 31, 2013

NIDA Marijuana Portfolio Discussion

May 23, 2013

NIDA’s Marijuana research portfolio was discussed—from basic science through services and policy research. Discussion focused on:

The most urgent research questions:

• Prospective studies in children adolescents to evaluate effects of

marijuana exposure on brain development and opportunity to

integrate across studies of brain development.

• Need to characterize the cannabinoids involved in marihuana’s effects

• Treatment and prevention studies

• Policy research

R Irannejad et al. Nature 000, 1-5 (2013) doi:10.1038/nature12000

Nb80–GFP Detects Activated b2-ARs in Plasma Membrane & Endosomes

Internalized b2-ARs Contribute to

cAMP response

Canonical GPCR Signalling Occurs Endosomes: assessment with conformational biosensors

(single-domain antibodies or nanobodies)

Cyclooxygenase-2 (COX-2) Modulate

Endocannabinoids (eCB): in vivo

• COX-2 catalyze formation of prostaglandins from arachidonic acid; target of NSAIDs.

• COX-2 inactivates 2-AG and AEA to produce prostaglandin-glycerol esters and ethanolamides.

• Evidence for the in vivo regulation of eCBs by COX-2 is lacking

LM-4131 mirrored PF-3845 (FAAH

inhibitor) in anxiety measures

Hermanson et al., Nature Neuroscience 16, 1291–1298 (2013)

POTENTIAL OF COX-2 INHIBITORS FOR

THE TREATMENT OF MARIHUANA

ADDICTION

Efficacy and Safety of TV-1380 as Treatment for Facilitation of Abstinence in Cocaine-Dependence

Phase II

Study Design: Allocation: Randomized Endpoint Classification: Safety/Efficacy Study 12-weeks Masking: Double Blind Official Title: Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Once-Weekly Intra-Muscular Injections of TV-1380 (150 mg/Week or 300 mg/Week) as Treatment for Facilitation of Abstinence in Cocaine-Dependent Subjects

Study Status: Currently recruiting participants

Estimated Study Completion Date: October 2014

Estimated Primary Completion Date: September 2014 (Final data collection date

for primary outcome measure)

New Treatment FOAs

Grand Opportunity in Medications Development for SUD (U01) PAR-13-270.

Issued: July 11, 2013; Open Date: February 27, 2013: Application due date(s): March 27, 2014, July 28, 2014, March 27, 2015,

July 28, 2015, March 28, 2016, July 28, 2016

To accelerate the development of medication for SUD by encouraging research to support a diverse array of preclinical and/or clinical research s.

Strategic Alliances for Medications Development to Treat Substance Use Disorders (R01) PAR-13-334

Issued: August 19, 2013; Open Date: February 27, 2014; Application due date(s): March 27, 2014, July 28, 2014, March 27, 2015, July 28, 2015,

March 28, 2016, July 28, 2016

To support research that advances compounds towards FDA approval by leveraging resources of outside organizations, such as pharmaceutical and biotechnology companies, private and public foundations, and small businesses.

Abuse-Resistant and Abuse-Deterrent Formulations and Devices to Avoid the Abuse, Misuse and

Diversion of Prescription Opioids by Patients (SBIR)(R43/R44) RFA-DA-14-013. Issued: July 15, 2013; Open date(s): September 11, 2013;

Application Due Date: October 11, 2013.

NIDA FOA

Represents a focused effort of NIDA on preventing diversion and misuse of

prescription opioids at the patient level. Among potentially important steps

towards the goal of safer opioid analgesics are the efforts to reformulate

medication so that an individual would not be able (abuse resistance) or

would not want (abuse deterrence) to divert the prescription drug, and to

create innovative medication dispensing devices/gadgets

Longitudinal Changes in Engagement in Care & Viral Suppression for HIV-infected IDU

Westergaard RP et al., AIDS 2013,

Jun 13. [Epub ahead of print]

Predictors of lapses in care (C)

& virologic failure (V) (adj. age

and year)

• active IDU (C, V)

• incarceration (C, V)

• no regular primary care (C)

• no provider constancy (C, V)

• no health insurance (C)

• alcohol use (V)

• crack use (V)

2013 Avant-Garde Awards

Warner Greene, M.D., Ph.D. Gladstone Institutes, SF, CA

HIV without AIDS: A radically different

approach to help the developing world

Richard Sutton, M.D., Ph.D. Yale University, NH, Connecticut

Host genetic control of HIV

Timothy Cardozo, M.D., Ph.D. NYU Langone Medical Center

Combined cocaine and HIV vaccine

CD4 T cells die of an inflammatory

programmed cell death (pyroptosis), which

involves caspase-1 activation.

Caspase-1 inhibitors are already in clinical

trials and this study will use the SIV model

to explore whether they can alter rates of

CD4 T-cell loss and progression to AIDS.

Whole exome sequencing of elite controllers

and members of their families to identify

genetic factors responsible for host control

of HIV.

Candidate genes identified from WES will be

subjected to in vitro functional studies.

Combined cocaine and HIV vaccine based on a

common protein scaffold

Aimed to develop an immunogen capable of

eliciting HIV-protective antibodies.

New HIV/AIDS FOAs

Integrating Substance Abuse Prevention and Treatment within HIV/AIDS Service Delivery Settings (R01) RFA-DA-14-011.

Issued: June 10, 1013; Open date: October 15, 2013;

Application due date(s): November 15, 2013.

Applications to test implementation strategies for integrating evidence-based SUS services with HIV care (including sexually-transmitted infection [STI] clinics) where screening for drug and alcohol problems can be integrated with screening for HIV and other conditions.

FY14 NIDA Avant-Garde Award Program for HIV/AIDS

Research (DP1) RFA-DA-14-008 Issued: May 30, 2013; Open date: October 6, 2013;

Application due date(s): November 6, 2013.

To support individual scientists of exceptional creativity who propose high-impact research.

November 8 - Frontiers in Addiction Research Mini-Convention*

• Emerging & Novel Aspects of Neuronal Transmission

• The Jacob P. Waletzky Memorial Lecture

• Extracellular RNAs in Neuroscience: Biology, Biomarkers, & Therapeutics

• Advances in High Resolution & Large Scale Imaging of Brain Networks &

Circuits

• The Role of the Basal Ganglia in Addiction

November 9-13 – NIDA participating in the NIH Neuroscience Exhibit Booth

November 11 – NIDA workshop* Transitioning Beyond the Postdoc:

Workshop for Early Career Investigators

November 12 – NIDA mini-symposium* New Insights into the Specificity&

Plasticity of Reward & Aversion Encoding in the Mesolimbic System.

* Pending official approvals

Society for Neuroscience (SfN) Annual Meeting

San Diego, CA - November 9-13, 2013

Insufficient reporting of methodological approaches is evident for pre-clinical studies

Trends Neurosci 2007; 30: 433-439 Adapted from Dr. S. Silberberg, NINDS

New HIV/AIDS FOAs

HIV/AIDS and Substance Use among Black/African American Women and Young MSM (R01) RFA-DA-14-010.

Issued: June 10, 2013; Open date: October 15, 2013; Application due date(s): November 15, 2013.

HIV/AIDS and Substance Use Among the Homeless and Unstably Housed (R01) RFA-DA-14-009.

Issued: June 10, 2013; Open date: October 15, 2013; Application due date(s): November 15, 2013.

Seeks applications 1) to conduct research that expands our understanding of the intersection between SUD & HIV among AA women & young AA MSM to develop &test interventions that improve HIV prevention and care s.

Encourages studies on the development, implementation, evaluation, and dissemination of effective HIV-prevention interventions, research related to the epidemiology of HIV and SUD, and health services in prevention and treatment services for the homeless s.