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
What’s New @ HHS/NIH?
Recent NIDA
Activities & Events
NIDA BUDGET
(Thousands)
2012
Actuals
NonAIDS
AIDS
TOTAL
2013
Operating Level
2014
PB
$733,076
$691,816
$739,326
$319,292
$300,749
$332,286
$1,052,368
$992,565
$1,071,612
Director’s Report to the
National Advisory Council on Drug Abuse
•
•
•
Budget Update
What’s New @ HHS/NIH?
Recent NIDA
Activities & Events
“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
NIH and BRAIN: How will it work?
• 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: NIH Working Group
Cornelia Bargmann, PhD (co-chair)
Joshua Sanes, PhD
The Rockefeller University
Harvard University
Bill Newsome, PhD (co-chair)
Mark Schnitzer, PhD
Stanford University
Stanford University
David Anderson, PhD
Terry Sejnowski, PhD
California Institute of Technology
Salk Institute for Biological Studies
Emery Brown, MD, PhD
David Tank, PhD
Massachusetts Institute of Technology
Princeton University
Karl Deisseroth, MD, PhD
Roger Tsien, PhD
Stanford University
University of California, San Diego
John Donoghue, PhD
Kamil Ugurbil, PhD
Brown University
University of Minnesota
Peter MacLeish, PhD
Morehouse School of Medicine
EX OFFICIO MEMBERS
Kathy Hudson, PhD
Eve Marder, PhD
National Institutes of Health
Brandeis University
Geoffrey Ling, MD, PhD
Richard Normann, PhD
Defense Advanced Research Projects Agency
University of Utah
John Wingfield, PhD
National Science Foundation
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 highpriority 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
Problem
•
•
Lack of reproducibility of published research findings.
Underlying issues:
–Poor education
–Poor evaluation
–Perverse reward incentives
Almost 2/3 of 67 in-house projects
could not replicate data published
by others
Prinz, Schlange and Asadullah
Bayer HealthCare
Nature Reviews Drug Discovery 2011; 10:712-713
Deficient reporting is widespread
Journals:
• Cell
• Nature
• Science
• Nature Medicine
• Nature Genetics
• Nature Immunology
• Nature Biotechnology
>500 citations
Translated to human
studies
Hackam and Redelmeier, JAMA 2006; 14: 1731-1732
Courtesy of Dr. S. Silberberg, NINDS
Addressing the Issues
• 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.
2.
3.
4.
Raise community awareness.
Enhance formal training.
Improve the evaluation of applications.
Protect the integrity of science by adoption of more systematic
review processes.
5. Increase stability for investigators.
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…
New Common Fund FOAs
NIH Transformative Research Awards (R01) RFA-RM-13-008
Due Date: October 4, 2013.
Supports individual scientists or groups of scientists proposing groundbreaking, exceptionally
innovative, original and/or unconventional research
NIH Director's New Innovator Award (DP2) RFA-RM-13-007
Due Date(s): October 25, 2013, October 17, 2014 & October 16, 2015.
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
NIH Director's Early Independence Awards (DP5)
RFA-RM-13-009
Due Date: January 31, 2014
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.
Funds are available for revisions to augment existing R01 to help meet the goals of
Collaborative Research on Addiction at NIH (CRAN)
Administrative Supplements to Promote Collaborative
Research on Addiction at NIH (CRAN): ComorbidityRelated Research (Admin Supp) PA-13-275
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
What’s New @ HHS/NIH?
Recent NIDA
Activities & Events
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
Percent Using in Past Month
10
8.3+
8.2+
8
7.9+
8.1+
8.3+
8.0+
6.2+
6.2+
6.1+
6.0+
6.0+
5.8+
2.7
2.7
2.5
2.7
2.9
2.8
0.9+
1.0+
0.8+
1.0+
1.0+
6
9.2
8.7
8.9
8.7
6.7+
6.9
7.0
2.8
2.7
0.7
Illicit Drugs
8.1+
7.3
Marijuana
6.1+
4
2
0
+
0.8+
2.5
0.7
2.4
2.6
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
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
Difference between this estimate and the 2012 estimate is statistically significant at the .05 level.
Psychotherapeutics
Cocaine
Hallucinogens
Daily or Almost Daily Marijuana Use in the Past
Year and Past Month among Persons Aged 12 or
Older: 2002-2012
Numbers in Millions
8
6.9
7
4
Used Marijuana on 20
or More Days in the
Past Month
5.4
Used Marijuana on
300 or More Days in
the Past Year
7.1
6.2+
6
5
7.6
4.8+
3.1+
4.9+
3.1+
4.9+
3.2+
5.1+
5.1+
5.1+
5.5+
4.6+
3.4+
3.6+
3.9+
5.0
4.1+
3.1+
3
2
1
0
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
+
Difference between this estimate and the 2012 estimate is statistically significant at the .05 level.
Changes in Marijuana Policy in the USA
Map Of States That Legalized Marijuana By 2004
passed laws legalizing MJ
Outcomes of Interest
Odds Ratio
2.5
2
1.81
1.92
1.5
1.03
1
0.5
0
Past Year MJ Abuse/Dependence
Past Year MJ Use
Past Year MJ Abuse/Dependence
Among Current Users
NESARC: National Epidemiologic Survey on Alcohol and Related Conditions
Cerda M et al. Drug and Alcohol Dependence 2012; 120: 22 – 27.
As of now 20 states in the USA
have approved the legalization
of medical marijuana
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
Availability of supplements to inform social, behavioral,
and public health impacts of recent US marijuana
legalization policies.
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
Canonical GPCR Signalling Occurs Endosomes:
assessment with conformational biosensors
(single-domain antibodies or nanobodies)
Nb80–GFP Detects Activated b2ARs in Plasma Membrane &
Endosomes
Internalized b2-ARs Contribute to
cAMP response
R Irannejad et al. Nature 000, 1-5 (2013) doi:10.1038/nature12000
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
POTENTIAL OF COX-2 INHIBITORS FOR
THE TREATMENT OF MARIHUANA
ADDICTION
Hermanson et al., Nature Neuroscience 16, 1291–1298 (2013)
Efficacy and Safety of TV-1380 as Treatment for
Facilitation of Abstinence in Cocaine-Dependence
Phase II
Study Design:
Endpoint Classification:
Masking:
Allocation: Randomized
Safety/Efficacy Study
12-weeks
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:
Estimated Study Completion Date:
Estimated Primary Completion Date:
Currently recruiting participants
October 2014
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.
NIDA FOA
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.
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
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)
Westergaard RP et al., AIDS 2013,
Jun 13. [Epub ahead of print]
2013 Avant-Garde Awards
CD4 T cells die of an inflammatory
programmed cell death (pyroptosis), which
Gladstone Institutes, SF, CA
involves caspase-1 activation.
HIV without AIDS: A radically different Caspase-1 inhibitors are already in clinical
approach to help the developing world
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.
Warner Greene, M.D., Ph.D.
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
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
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.
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.
Society for Neuroscience (SfN)
Annual Meeting
San Diego, CA - November 9-13, 2013
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