Closed Session - February 10th

  • Call to Order - Nora Volkow, M.D. Director, NIDA
  • Review of Policy and Procedures - Susan Weiss, Ph.D., Executive Secretary, National Advisory Council on Drug Abuse, Director, Division of Extramural Research, NIDA
  • Council Review of Grant Applications - Nora Volkow, M.D. Director
    • Division of Epidemiology, Services, and Prevention Research (DESPR) - Carlos Blanco, M.D., Ph.D., Director
    • Division of Therapeutics and Medical Consequences (DTMC) - Phil Skolnick, Ph.D., D.Sc. (hon.), Director
    • Division of Neuroscience and Behavioral (DNB) - Joni Rutter, Ph.D., Director
  • End of Closed Session

Open Session - February 10th

  • Opening and Welcome New Members- Nora Volkow, M.D. Director, NIDA
  • NIDA Director's Report - Nora Volkow, M.D., Director, NIDA
  • Council Discussion - Council Members
  • Genotype-Tissue Expression (GTex) Project - Kristin Ardlie, Ph.D., Director, Biological Samples Platform, Broad Institute of Harvard and MIT
  • New AIDS Priorities - Bob Eisinger, Acting Associate Director, AIDS Research, NIH
  • Changing Landscape of Tobacco Products - Laura Bierut, M.D., NACDA Council Member and Professor of Psychiatry, Washington University School of Medicine, St. Louis, MO
  • FOA Concept Clearances - NIDA Staff
  • Public Comments
  • Adjourn

Minutes - February 10, 2016

The National Advisory Council on Drug Abuse convened its 122nd meeting at 8:30 a.m. on February 10th, 2016 in Conference Rooms C & D, 6001 Executive Boulevard, Bethesda, Maryland. The closed portion of the meeting held on February 10th was for the purpose of reviewing applications for Federal grant assistance and was open only to Council members and Federal employees. The open portion, which was open to the public on February 10th, began at 10:30 a.m. The Council adjourned on February 10, 2016 at 3:55 p.m.

Council Members Present
Anne Andorn, M.D.
Judith Auerbach, Ph.D.
Laura Bierut, M.D.
Julie Blendy, Ph.D.
Regina Carelli, Ph.D.
John Carnevale, Ph.D.
Arthur Dean, M.A.
Eric Verdin, M.D.

Council Members Present
James Hildreth, M.D., Ph.D. 
Steffanie Strathdee, Ph.D. 

Council Chair
Nora Volkow, M.D.

Executive Secretary
Susan Weiss, Ph.D.

Ad-Hoc Council Members Present
Marie Dyak
Jay Giedd, M.D.
Lisa Marsch, Ph.D.
Edward Nunes, Jr. M.D.
Robert Rancourt, J.D. 

Federal Employees Present

Jane Acri, Ph.D.
Will M. Aklin, Ph.D.
Ann Anderson, M.D., M.P.H.
David Anderson, M.A.
Nathan Appel, Ph.D.
Joellen Austin, M.S., M.P.A.
Beth Babecki, M.A.
Carlos Blanco, M.D., Ph.D.
Kris Bough, Ph.D.
Cheryl Boyce, Ph.D.
Maureen Boyle, Ph.D.
Mark Caulder, M.S., M.P.H.
Naresh Chand, DVM, Ph.D.
Nora Chiang, Ph.D.
Wilson Compton, M.D., M.P.E.
Kevin Conway, Ph.D.
Jessica Cotto, M.P.H.
Aria Crump, Ph.D.
David Daubert
Genevieve deAlmeida-Morris, Ph.D.
Bethany Griffin Deeds, Ph.D.
Julius Diggs
Gaya Dowling, Ph.D.
Sarah Duffy, Ph.D.
Emily Einstein, Ph.D.
Kathy Etz, Ph.D.
Matthew Finger, M.A.
Nick Gaiano, Ph.D.
Stacy Gardner
Mimi Ghim, Ph.D.
Udi Ghitza, Ph.D.
Meyer Glantz, Ph.D.
Pamela Goodlow
Harold Gordon, Ph.D.
Steven Grant, Ph.D.
Aidan Hampson, Ph.D.
Paul Hillery, Ph.D.
Nahla Hilmi, M.P.H.
Katia Howlett, Ph.D., M.P.H., M.B.A.
Julie Huffman
Kristen Huntley, Ph.D.
Richard Jenkins, Ph.D. Dionne Jones, Ph.D.
Angelina Jordan
Shoshana Kahana, Ph.D.
Mary Kautz, Ph.D. Jag Khalsa, Ph.D.
Heather Kimmel, Ph.D.
Elena Koustova, Ph.D., M.B.A.
Philip Krieter, Ph.D.
Elizabeth Lambert, M.Sc.
Guifang Lao, M.D., Ph.D.
Geoffrey Laredo, M.P.A.
Minna Liang, Ph.D.
Yu Lin, M.D., Ph.D.

Flair Lindsey
Roger Little, Ph.D.
Jacqueline Lloyd, Ph.D.
Anita LoMonico
Marsha Lopez, Ph.D.
Raul Mandler, M.D.
David McCann, Ph.D.
Susan McGuire, Ph.D.
Gerald McLaughlin, Ph.D.
Ivan Montoya, M.D.
Anita Mudgett
Jacques Normand, Ph.D.
Samia Noursi, Ph.D.
Moira O’Brien, M. Phil.
Brian O’Laughlin
Hiromi Ono, Ph.D.
Christina Page
Lanette Palmquist
Karran Phillips, M.D.
Nancy Pilotte, Ph.D.
Jonathan Pollock, Ph.D.
Dena Procaccini, M.A. Vishnudutt Purohit, D.V.M, Ph.D.
Thomas Radman, Ph.D.
Tanya Ramey, MD, Ph.D.
Jagadeesh Rao, Ph.D.
Rao Rapaka, Ph.D.
Carmen Rosa, M.S.
Natisha Rowe Jose Ruiz, Ph.D.
Joni Rutter, Ph.D.
Christine Salaita, M.S., R.D.
Catherine Sasek, Ph.D.
Irina Sazonova, Ph.D.
Jeffrey Schulden, M.D.
Myriam Selmane
Belinda Sims, Ph.D.
Hari Singh, Ph.D.
Karen Sirocco, Ph.D.
Phil Skolnick, Ph.D., D.Sc.
Roger Sorensen, Ph.D.
Jack Stein, Ph.D.
Shelley Su, Ph.D.
Karyl Swartz, Ph.D.
Mark Swieter, Ph.D.
Betty Tai, Ph.D.
David Thomas, Ph.D.
Shang-Yi Tsai, Ph.D.
Carolyn Tucker
Susan Volman, Ph.D.
Kevin Walton, Ph.D.
Eric Wargo, Ph.D.
Cora Lee Wetherington, Ph.D.
Tisha Wiley, Ph.D. Da-Yu Wu, Ph.D. 

Members of the Public Present
Victoria Green
Victor Prikhodko, M.B.A. - Kelly Services
Marushka Silveira, Ph.D.
Frank Snyder, Ph.D. - Purdue University
Roy Walker, M.B.A. - Synergy Enterprises, Inc. 

Closed Portion of the Meeting – February 10, 2016

  1. Call to Order

    This portion of the meeting was closed to the public in accordance with sections 552b(c) (4) and 552b(c) (6), Title 5, U.S. Code and section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. Appendix 2). 

    Dr. Nora Volkow, Director, NIDA, called the meeting to order and welcomed the Council and staff. She reminded those present that the Federal Advisory Committee Act applies to Council meetings and that this portion of the meeting was closed to the public. 

    Dr. Susan Weiss, Executive Secretary, summarized relevant NIH policies, provided detailed instructions on Council review procedures, and reminded those present about NIH confidentiality and conflict of interest policies. 

  2. Application Reviews

    In turn, the Director or a designee for the Division of Epidemiology, Services and Prevention Research, the Division of Therapeutics and Medical Consequences, and the Division of Neuroscience and Behavior presented their applications for consideration by the Council. For each, Council provided concurrence with the initial scientific reviews en bloc. Council also approved Administrative Supplements. Relevant applications were presented to Council for Special Council Review, and Council agreed with program assessments. All Trans-NIH Initiatives, i.e., Common Fund applications and NIDA Secondary applications also received Council concurrence. 

    Members must absent themselves from the Council meetings during discussion of, and voting on, individual applications from their own institutions or other applications in which there is a conflict of interest, real or apparent. Conflicts of interest statements were signed by each member of the Council. Members were not required to leave if an application in conflict with that member was acted upon en bloc

Open Portion of the Meeting – February 10, 2016

  1. Call to Order

    Dr. Nora Volkow, Director, NIDA, called the open portion of the meeting to order and welcomed all attendees. She began by introducing five ad-hoc council members: Ms. Marie Gallo Dyak, Dr. Jay N. Giedd, Dr. Lisa A. Marsch, Dr. Edward V Nunes, Jr., and Judge Robert Rancourt: 

    Marie Gallo Dyak is Executive Vice President of Program Services and Government Relations to the Entertainment Industries Council, Inc. She is responsible for concept development and implementation of EIC programs and special projects primarily involving the entertainment industry and health and social issues. She is also Co-Executive Producer of the PRISM Awards. The PRISM Awards spotlights creative contributions that best exemplify the entertainment industry's sincere efforts to use its unique platform with access to audiences to present accurate information through depiction of substance use disorders and mental health issues. Ms. Dyak is an Emmy® Award winning producer, having produced educational and training videos on such topics as substance abuse and addiction, foster care, multicultural families, PET cardiac scanning procedures, and inhalant abuse

    Dr. Jay Giedd is Professor of Psychiatry at the University of California, San Diego, and Director of the Division of Child and Adolescent Psychiatry at the Rady Children’s Hospital-San Diego. In addition, he is adjunct Professor at Johns Hopkins School of Public Health in the Department of Family and Reproductive Medicine. Over the past 25 years Dr. Giedd has combined brain imaging, genetics, and behavioral analysis to explore the path and influences of brain development in health and illness. As one of the most highly cited neuroscientists of his generation, his over 200 scientific publications have had a transformative impact on medicine, psychology, education, judicial, and public policy. 

    Dr. Lisa A. Marsch is Director of the Center for Technology and Behavioral Health (, the Director of the Dartmouth Psychiatric Research Center, and a faculty member within the Department of Psychiatry at the Geisel School of Medicine at Dartmouth College. Dr. Marsch has led a line of research focused on the development and evaluation of technology-based interventions targeting substance abuse treatment, as well as HIV prevention, mental health, and other areas of behavioral health. These technology-based therapeutic reflect an integration of science-based behavioral interventions with evidence-based informational technologies. This research has provided novel empirical information regarding the role that technology may play in improving the prevention and treatment of substance use disorders and other behavioral health issues by improving quality of care, access to care, and treatment outcomes, while reducing costs of care. 

    Dr. Edward Nunes Jr. is Professor of Psychiatry at Columbia University and New York State Psychiatric Institute and a Board Certified psychiatrist and addiction psychiatrist, who has devoted his career to the development and evaluation of new treatments for substance use and related mental health conditions. Dr. Nunes has been principal investigator or collaborator on numerous NIH-funded studies and, since 2000, has served as principal investigator of the Greater New York Node in NIDA’s Clinical Trials Network, which is committed to the evaluation and dissemination of effective treatment methods for substance use disorders in community-based settings. He thus has extensive experience in the implementation and evaluation of treatment innovations in “real-world” treatment settings. His past work includes the development and evaluation of medications and behavioral treatments for co-occurring alcohol/drug and mood/anxiety disorders, treatments for cocaine and opioid dependence, design of treatment evaluation studies, and methods for training community-based clinicians in evidence-based practices. 

    Judge Robert Rancourt, J.D., is a Minnesota District Court Judge. Since his appointment to the bench in 2002, one of his assigned tasks was to address the impact of alcohol and other drugs on all case types the court addresses. Judge Rancourt has presented nationally and internationally to judges, policy groups, and those in the recovery field on the area of evidence-based practices to address those who appear before the Court with addiction and mental health issues. 

    Dr. Volkow reminded the Council and audience that the meeting was open to the public in compliance with the Government in the Sunshine Act and indicated that time would be provided for public comment. She then called attention to future Council meetings: May 3-4, 2016, September 8, 2016, and February 14-15, 2017. September Council will be a one-day meeting. She reminded all attendees that the CRAN Council meeting will take place, the next day on February 11, 2016 and will be held at Fischer’s Lane. 

  2. Consideration of the Minutes of Council

    The Minutes of the NIDA October 2015 meeting were unanimously approved as written.

  3. NIDA Director’s Report - Nora Volkow, M.D., Director, NIDA

    Dr. Volkow began her presentation by introducing NIDA’s new Executive Officer, Ms. Joellen Austin. Ms. Austin has formidable experience at NIH as the previous Executive Officer (EO) for the National Institute of Neurologic Diseases and Stroke (NINDS), as well as the National Institute of Environmental Health Sciences (NIEHS). Dr. Volkow asked members of Council, as well as the audience to join her in welcoming Ms. Austin to NIDA. She also recognized the remarkable work of Mr. Dave Daubert, Deputy Executive Officer, for his role as the Acting EO during the time of transition. 

    Dr. Volkow then gave an update on the budget. The Presidential Budget for FY 2016, is a 4 percent increase over FY 2015’s budget and places NIDA’s total budget at a little over $1 billion, with the AIDS allocation at approximately one third of the total budget; however, due to reconfiguration of NIH’s Office of AIDS research priorities, there is a slight decrease in overall AIDS funding. The FY 2017 proposed budget is the same as that for 2016. She then provided NIDA’s FY 2015 Actuals budget portfolio that indicated the Division of Neuroscience and Behavior received 39% of the budget, followed closely by the Division of Epidemiology, Services and Prevention Research at 36%, then the Division of Therapeutics and Medical Consequences at 20%, and the remaining budget covered the Center for the Clinical Trials Network, the Intramural Research Program and administrative costs. 

    Turning to what is new at NIH; Dr. Volkow began with the BRAIN Initiative. Begun by the President in 2014, the initiative is targeting the development of tools and technologies as a way to better advance the understanding of how the brain works. In FY 2014, the BRAIN Initiative funded projects totaling $46.1 million. Most of the funds came from a congressional allocation, the remainder the National Institute of Mental Health (NIMH), the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Drug Abuse (NIDA), and the National Institute of Biomedical Imaging and Bioengineering (NIBIB). Funding went up to $85 M in FY 2015, which included newly allocated funds, funds from the ICs and funds from the NIH Blueprint for Neuroscience Research. In FY 2016, the BRAIN Initiative received $85 million in new funding from Congress that allowed the launch of several extremely exciting projects. For upcoming FY 2017, $45 million has been allocated. FY17 is considered a churn year, meaning that projects started in FY 2014 will end. The priority for funded projects has been to develop tools and technology to help classify cells, to identify circuits at the macro and micro level, and to begin investigating the functions of each. Focus has also expanded to better understand the role of glial cells.

    Many of the FY16 Funding Opportunity Announcements (FOA) will be reissues of previous ones. There are a couple of new ones as well, such as one related to sharing and propagation of the tools being developed via the other BRAIN initiatives and another on theories, models and methods for analysis of complex neuroscience data. 

    Dr. Volkow next spoke about the Precision Medicine Initiative (PMI), a new model of patient-powered research that promises to accelerate biomedical discoveries and provide clinicians with new tools, knowledge, and therapies to select which treatments will work best for which patients. The President’s budget requested $215 million for FY 2016; of which $200 million will come to NIH with $130 million to develop a national research cohort of a million or more volunteers to propel our understanding of health and disease and set the foundation for a new way of doing research through engaged participants and open, responsible data sharing; and $70 million for NCI to scale up efforts to identify genomic drivers in cancer and apply that knowledge in the development of more effective approaches to cancer treatment. A PMI Working Group of the Advisory Committee to the NIH Director (ACD), including experts from many disciplines and sectors, was established to help plan for the creation and management of the PMI research cohort. The PMI Working Group’s report of recommendations was delivered to the ACD in September 2015. Out of these recommendations, four FOAs were released in November, 2015: 1) PMI Cohort Program Coordinating Center (UC2); 2) PMI Cohort Program Healthcare Provider Organization Enrollment Centers (UG3/UH3); 3) PMI Cohort Program Participant Technologies Center (U24); and 4) PMI Cohort Program Biobank (U24). 

    The advantage to NIDA of the PMI initiative is the opportunity to collect data to understand how the use of drugs influences medical outcomes; as well as gathering information on whether a decrease in the amount of a substance used has a beneficial effect on health outcomes. Dr. Maureen Boyle is leading NIDA in efforts to create a plan to ensure that information on substance use disorders and mental health conditions can be used in this NIH research effort. 

    Dr. Volkow then announced the recent departure of Dr. Tom Insel, Director, National Institute of Mental Health. Dr. Volkow is co-chair along with Dr. Walter Koroshetz (NINDS) of the selection committee for a new NIMH Director. She indicated that there are a number of qualified applicants, and expressed optimism that she and her colleagues would be able to provide Dr. Francis Collins, Director of NIH, with a short list of high quality candidates. 

    Dr. Volkow then provided an update on the NIH Strategic Plan, which was released on December 16, 2015. The four major objectives are: 1) Advance Opportunities in biomedical research, in fundamental science, treatment and cures, and health promotion and disease prevention; 2) Foster Innovations by setting NIH priorities to enhance nimbleness, consider burden of disease and the value of permanently eradicating a disease, and advance research opportunities presented by rare diseases; 3) Enhance Scientific Stewardship by recruiting and retaining an outstanding biomedical research workforce, enhancing workforce diversity and impact through partnerships, ensuring rigor and reproducibility, optimizing approaches to inform funding decisions, encouraging innovation, and engaging in proactive risk management practices; and 4) Excel as a Federal Science Agency by managing for results, developing the “science of science,” balancing outputs with outcomes, conducting workforce analyses, continually reviewing peer review, evaluating steps to enhance rigor and reproducibility, reducing administrative burden, and tracking effectiveness of risk management in decision making. 

    She then transitioned to the NIDA 2016-2020 Strategic Plan that was also released in December 2015. There are four goals: 1) Basic Science, to identify the biological, environmental, behavioral, and social causes and consequences of drug use and addiction across the lifespan; 2) Prevention, to develop new and improved strategies to prevent drug use and its consequences; 3) Treatment, to develop new and improved treatments to help people with substance use disorders achieve and maintain meaningful and sustained recovery; and 4) Public Health, to increase the public health impact of NIDA research and programs. Furthermore, the Strategic Plan’s priority areas include: 1) understanding the complex interactions of factors influencing drug use trajectories; 2) accelerating development of treatments; 3) addressing real-world complexities; and 4) advancing bidirectional translation. 

    Dr. Volkow went on to highlight NIDA priorities, beginning with Prevention Research. She began by presenting the results of the 2015 Monitoring the Future Study, an annual study conducted by the University of Michigan that assesses prevalence rates by surveying approximately 45,000 children across the United States, covering both public and private schools from grades 8-12. Overall, there have been significant decreases in drug use from 2014 to 2015. The areas that continue to demonstrate stable use are marijuana, e- cigarettes, amphetamines, in particular, Adderall. Non-medical use of Vicodin and Oxycontin, as well as sedatives have seen a significant decrease, likely attributable to the aggressive prevention campaigns. Beginning in 2012, the study began asking about synthetic cannabinoids (e.g., Spice), and there has been a significant decrease in percentage of students reporting its use in recent years. Synthetic 

    cannabinoids have a very high affinity for CB1 receptors and result in very serious adverse effects such as cerebrovascular accidents and psychosis. In addition, use of heroin among teenagers continues to decrease, which is reassuring considering the prevalence among adults and the recent cost reductions as it is shipped from Mexico in bulk. Furthermore, use of licit drugs, such as cigarettes and consumption of alcohol, continues to decline. Dr. Volkow then showed two marijuana use trajectories: one reporting percent students reporting use in past year, and the other showing the percent students reporting daily use. Both indicate that use has been stable over the past five years. The main source of marijuana among 12th graders in 2012-2015 is from friends, and in states with approved medical marijuana, from someone else’s or their own prescriptions. She then referred to Dr. Giedd’s work as it has shown that the human brain undergoes significant changes during adolescence and places young people at a higher risk for becoming addicted if they take drugs during this period of their development. 

    This led to an update into the Adolescent Brain Cognitive Development (ABCD) project. It is an NIH collaborative project with NIDA, National Institute of Alcohol Abuse and Addiction (NIAAA), National Cancer Institute (NCI), National Institute of Mental Health (NIMH), National Institute on Minority Health and Health Disparities (NIMHD), National Institute of Child Health and Human Development (NICHD), National Institute of Neurological Disorders and Stroke (NINDS), and the Office of Behavioral and Social Sciences Research (OBSSR). The ABCD project was launched last year and very ably led by Dr. Susan Weiss, who has since recruited Dr. Gayathri Dowling as Project Director. The objective of this project is to recruit and follow 10,000 children over a 10 year period with detailed phenotypic characterization and frequent evaluations, including brain imaging studies, during the critical transition period from 9-10 years old to age 20. The ABCD study will provide open access to data that will yield critical insights into the foundational aspects of adolescence that shape a person’s future. 

    Dr. Volkow then discussed NIDA Treatment Research. She presented statistics from the Centers for Disease Control and Prevention (CDC) from 1999-2014. There has been a steady and alarming increase in opioid analgesic overdose deaths in the U.S. propelled by the abuse of prescription opioids. In 2012 and 2013, the data appeared to indicate a plateau in deaths related to opioid use, however, the numbers from 2014 exceed that of any other previous year. In addition, there seems to be a parallel and dramatic increase in heroin overdose fatalities in 2013 and 2014. This issue highlights the urgency of addressing this epidemic, and HHS has implemented an aggressive and proactive approach to opioid-drug related addiction, overdose, and death. This approach includes: 1) Providing training and educational resources, including updated prescriber guidelines, to assist health professionals in making informed prescribing decisions; 2) increasing use of naloxone; and 3) expanding the use of Medication-Assisted Treatment (MAT). 

    She then went on to explain NIDA’s action plan and began by stating that at least 100 million Americans suffer from chronic pain, with limited options for pain management. Opioids are the best option for treating acute pain, but there is scant evidence for their effectiveness (or any other approaches) in managing chronic pain. However, physicians are limited in what they can prescribe. A recent study in the Annals of Internal Medicine that followed a cohort of 2900 patients admitted with an opioid overdose for up to a year. It divided the patients based on the dose of opioids prescribed: low (50 mg of morphine equivalent); intermediate (50-100 mg equivalent); and high (over 100 mg equivalent). The study discovered that despite the fact that opioid discontinuation after overdose is associated with lower risk for repeated overdose, almost all patients continued to receive prescription opioids after an overdose. In addition, the groups on intermediate and high doses of opioids were between 15-17% more likely to have a second overdose episode. This study highlights the need to implement better practices for the use of opioids in the treatment of pain. 

    An important effort to address this issue comes from the NIH’s Pain Consortium, in which NIDA participates. The Pain Consortium has created Centers for Excellence in Pain Education (CoEPEs) to act as hubs for the development, evaluation, and distribution of pain management curriculum resources for medical, dental, nursing, and pharmacy schools. The centers must develop materials to create one case-based education module per year as the main deliverable. The CoEPEs must also test the efficacy and impact of these modules and disseminate their findings. In September 2015, 11 CoEPEs were funded, and she listed the names of the recipient academic institutions. 

    Dr. Volkow then presented two studies, one published by Walley et al., in British Medical Journal 2013 showing that opioid overdose related deaths were reduced in communities that implemented nasal naloxone distribution programs; and another study by Rando et al., American Journal of Emergency Medicine, 2015 indicating that intranasal naloxone administration by police first responders was associated with decreased overdose deaths in Ohio. The Division of Therapeutics and Medical Consequences (DTMC) has been working for three years with two pharmaceutical companies to develop a formulation of naloxone that would be user friendly. One of the companies received approval from the FDA on November 18, 2015 for Narcan naloxone nasal spray at a cost of $37.50 per 4 mg dose, which makes it very accessible. 

    Another study that she presented related to Medication Assisted Therapy (MAT), published by D’Onofrio in the Journal of the American Medical Association (JAMA) in 2015, showed that emergency department-initiated buprenorphine increased engagement in addiction treatment, reduced self-reported illicit opioid use, and decreased use of inpatient addiction treatment services. The concern with use of buprenorphine is that, similar to methadone, it requires frequent dosing. The FDA is expected to release a final decision on the approval of an extended release implantable buprenorphine called Probuphine. Probuphine only needs to be taken every 6 months, which is expected to improve compliance. 

    Next, Dr. Volkow spoke about the HIV and Drugs priority area. There are new NIH AIDS research priorities that came out as a function of the Advisory Council to the NIH Director. The following priorities for HIV research were identified: 1) Reduce incidence, including vaccines; 2) Next generation of HIV therapies with better safety and ease of use; 3) Research toward a cure; and 4) HIV-associated comorbidities and co-infections. Dr. Volkow stated that the cross cutting areas that relate to NIDA are basic research, health disparities and training. In order to reduce the incidence of HIV, NIDA needs to address HIV in substance abusers that are at higher risk for comorbidities. Members of NIDA Advisory Council, including Drs. Judy Auerbach, James Hildreth, Steffanie Strathdee, and Eric Verdin, among other experts and NIDA scientists have formed the NIDA Council HIV Workgroup and had their first meeting on September 22, 2015. The workgroup is charged with providing advice and making recommendations on future directions for NIDA’s HIV/AIDS research priorities. A new Funding Opportunity Announcement was issued on October 30, 2015: HIV/AIDS High Priority Drug Abuse Research (R01) to stimulate high priority research relevant to drug abuse and HIV/AIDS including: 1) Studies on optimization of seek, test, treat and retain (STTR), which ties into the OAR priority of Reduced incidence; 2) Implementation research on integration of drug abuse treatment and HIV care to optimize HIV outcomes; 3) Implementation of STTR in prison and jail settings (where minorities are disproportionately represented) and upon release; 4) Studies on drug-drug interactions between current or potential new HIV/AIDS antiretroviral therapies and drugs of abuse, medications to treat addiction, and hepatitis C (HCV) medications; and 5) Studies to determine how exposure to drugs and cycles of abuse and withdrawal affect latency and reservoir size and persistence. Goals 2 through 5 would all fall under OAR’s HIV-associated comorbidities priority area. 

    In addition, suggestions from the workgroup have contributed to the issuing of 5 RFAs in FY 16, and 5 RFAs for FY17. Concept clearances will be presented for the FY 17 FOAs in the afternoon by various NIH extramural program officials. She also stated that Dr. Robert Eisinger, Acting Director of the Office of AIDS Research at NIH, will be presenting to Council in the afternoon. 

    Next Dr. Volkow moved on to NIDA hosted events. She first spoke about National Drug and Alcohol Facts Week, a program initiated by Carol Krause, Public Information and Liaison Branch Chief at NIDA, that has been going on for several years. She announced that NIAAA joined NIDA this year for an expanded program, which was held January 25-31, 2016. It broke all records and stimulated more than 2000 events around the United States and in over 14 other countries. Over 7000 questions were submitted, NIAAA, NIMH and the FDA Center for Tobacco Policy also participated, and the transcript will soon be published on the NIDA for Teens web page. 

    Another joint project by NIDA, NIAAA, NINDS, National Center for Complementary and Integrative Health (NCCIH), and NIMH is the Marijuana and Cannabinoids: A Neuroscience Research Summit that will be held on main campus NIH on March 22-23, 2016. The purpose is to learn about the endogenous cannabinoid system, the effects of cannabinoids on the brain, the adverse effects versus the potential medical therapeutic effects, as well to discuss policy implementation and the implications of changing marijuana laws on our country. 

    She then presented the Principles of Substance Abuse Prevention for Early Childhood: A Research-Based Guide that NIDA has produced. This is the fourth in a series of evidence-based principles booklets on: Drug Addiction Treatment, Adolescent Substance Use Disorder Treatment, and Drug Abuse Treatment for Criminal Justice Populations. It includes supplemental sections for researchers, policymakers and practitioners; it is web-based with easy-to-navigate, print-friendly chapters viewable on desktop, phone or tablet; and has selected sources with information on research-based early childhood drug prevention programs. Dr. Volkow asked Council members for their input and feedback. 

    Last, Dr. Volkow indicated that previous research on modafinil for cocaine abuse has not been very encouraging or statistically significant. Recently, a study published by Kampman et al., Drug and Alcohol Dependence 2015 showed that subjects who received modafinil were 23 percent more likely to abstain from cocaine use than subjects on placebo. In addition, both nurse practitioner and subjects’ self-rating of “cravings very much improved” while on modafinil were significantly better than those on placebo. In parallel, another study recently published reported that individuals on modafinil improved their sleeping pattern, and in turn significantly reduced cocaine cravings. These two studies, along with re-analysis done by Charles Dackis, indicate that modafinil might be a good therapeutic option for cocaine use disorder. 

    Council thanked Dr. Volkow for her presentation. Dr. Verdin began the discussion by stating that opioids have always been a part of the armamentarium of physicians and asked what changed in the early 2000s to fuel the results she shared. Dr. Volkow responded that in 2000, the Joint Commission for the Accreditation of Hospitals required hospitals to evaluate and properly treat patients with pain. However, this recommendation did not come with a parallel increase in the education of physicians on how to manage pain or how to properly prescribe and monitor opioid use. Dr. Laura Bierut added that there is limited data on the effects of opioids for pain management in the long-term, for more chronic pain and commended NIDA’s efforts with the NIH Pain Consortium on researching new options for pain management, while minimizing the risks of substance use disorders. Dr. Auerbach added that there also needs to be a distinction between physical and psychological/emotional pain. Dr. Volkow agreed that there is evidence that depression, as well as chronic stress and emotional trauma, influence sensitivity to pain, and she concurred with the need for further study in this area across all of NIH. Another line of questions was on the risk of children who are physically abused and might have sustained a concussion, and if the ABCD study is planning on looking at this issue. Dr. Volkow stated that all children participating in the study will be fully evaluated, both physically and psychologically for any related effects. The final question was related to the Patient-Reported Outcome Measurement Information System (PROMIS), where Dr. Bierut was concerned that the substance use domains were secondary on the soon to be released measures. Dr. Kevin Conway, Deputy Director of DESPR stated that the PROMIS Initiative is an item bank that is used to provide measures of health status and functioning across multiple domains. He added that NIDA has generated sufficient evidence, which has helped move substance use items in the queue for inclusion into the PROMIS item bank. 

  4. The Genotype-Tissue Expression (GTEx) Project: Updates and Analysis - Kristin Ardlie, Ph.D., Broad Institute

    Dr. Ardlie began her presentation with background information on the Gentoype-Tissue Expression (GTEx) project. It began approximately five years ago riding on the successes of large scale genetic genome-wide association studies (GWAS) that have identified hundreds of common DNA variants associated with multiple complex diseases and traits. One of the factors that limited the utility of such approaches to link diseases to genes was that the majority of GWAS markers lie in noncoding intergenic introns of the genome A more valuable approach was to correlate the presence of the various GWAS markers of disease with the quantitative expression of downstream genes via a method called expression Quantitative Trait Loci (eQTL). The challenges in using eQTLs to interpret disease associations are: 1) it is necessary to measure eQTLs during relevant time periods in disease-relevant tissues or cell types, 2) most human tissue types are hard to obtain; and 3) because these types of studies are correlative, large sample sizes are required for statistical power. GTEx was designed to address these challenges and to do so in all sorts of human organs and tissues. 

    GTEx is an NIH Common Fund initiative led by the National Human Genome Research Institute (NHGRI) and the National Institute on Mental Health (NIMH), with many other NIH institutes and centers, including NIDA, having been actively involved as well. The GTEx project goals were to characterize the regulatory architecture of the human genome and to understand the role of genetic variation on gene expression variation across a wide range of non-diseased human tissues. This in turn would create an atlas of human tissue gene expression, a normal database as it were, from which it would be possible to interpret disease effect compared to a reference normal. In addition, another goal was to create a comprehensive resource database of cis- and trans-eQTLs to understand the role of genetic variation on gene regulation to enhance and interpret GWAS studies.

    She then moved on to the scope of the GTEx project. The project began with a pilot to determine if acceptable quality of RNA could be obtained from deceased donors. Having shown this was possible, the project scaled up rapidly to enroll 960 post-mortem donors (including 400 from which brain materials could be sampled), and up to 53 types of tissue were collected per donor. The goal is to DNA sequence each donor, and as it stands now, whole genome and whole exome sequencing are being done on all donors; also to perform RNA sequencing as a means of assessing gene expression on over 25,000 tissues or an average of about 25 per donor. The study collects clinical and histopathology information on all of the donor tissues. Moreover, aside from the gene expression assays, there have been additional add-on studies performed as well, including an ethical, legal and social implications of the genomics research (ELSI) study of donor families; assays of proteins, somatic DNA mutations, DNAse1 hypersensitivity sites, teleomere length, among others. This will create a very rich resource. In addition to the data access, the samples that have been collected remain in the sample bank and are accessible for those who want to add to and enrich the resource. 

    Dr. Ardlie then pointed out that what makes GTex particularly unique. There are many studies of assays involving a number of cells or tissues. There are also other studies, even of eQTLs and gene regulation that have involved many donors, but few cells or tissues. GTEx is unique in that it spans both of these dimensions, multi-donors and multi-tissues at the same time, and it has never been done before. 

    Next, she spoke about the data types and production. GTEx begins with a donor from which biospecimen sourcing sites obtain the samples and process them. The donor must have a low postmortem interval (PMI), such as an organ transplant donor, with PMI of less than 24 hours to keep ischemic time down. The age range is between 21 and 70 years old, without a history of cancer or cachexia, and no history of long-term ventilator use. A brief medical history and toxicology screen is also obtained. Blood and time-sensitive samples are shipped to the Laboratory Data Analysis and Coordinating Center at the Broad Institute. There, whole blood samples provide DNA for genotyping; RNA (using PAXgene tubes) to be used as a reference to blood-derived RNA collected from living donors in other studies; and RNA from cultures of lymphoblastoid cells derived from resting B cells infected with Epstein Barr Virus. In addition, RNA is derived from fibroblasts cultured from fresh skin samples. Up to 53 tissue types are collected per donor, and they are shipped to a central biospecimen bank, where pathology is undertaken on every single tissue sample. When a brain is collected, it is iced and shipped to the University of Miami Brain Bank, where they do a careful dissection of 9 to 11 sub-regions. Snap frozen brain tissue is then sent to the Broad Institute to isolate RNA and DNA, where molecular DNA and RNA analyses are conducted. 

    Dr. Ardlie discussed the current donors’ collection status. The collection end goal of 960 donors has been reached, 534 non-brain and 426 brain donors. Non-brain donors average 30 tissues per donor, with an average PMI of 3.5 hours. The brain donors average more than 30 tissues per donor because they have brain sub-regions, and have an average PMI of 14.3 hours. As for the donor demographics, two thirds are male with 84% white, 14% black or African American, and less than 1% for other races. The average age range is between 50-60 years old. Dr. Ardlie then showed a graph with the many types of tissues collected; currently there have been close to 30,000 tissues collected from 45 sites. 

    Data are being released as they become available. The first data set was what was produced in the pilot and came from 175 donors and about 1,600 tissue samples. The most recent release involves data from about 450 donors and about 7,000 tissue samples and represents roughly the mid-point of the study. All of the primary data such as the metadata, the phenotypes, the histology, the genotype data, which is individually identifiable, and the raw expression data file have been released into the National Center for Biotechnology Information’s database of Genotypes and Phenotypes (dbGaP) and are available for use. As of December 2015, there have been close to 350 applications for those data. dbGaP data usage spans disease-specific studies, IPS cell generation, selection, population, structure, GWAS studies and splicing an isoform variants, among others. The most common study is cancer analyses, especially among those studying brain and lung tissues. This is a tremendous normal reference database that is being used for disease studies. Once the data is analyzed and stripped of identifiable information, the data goes into the GTEx portal, which is housed at the Broad Institute. It includes the eQTLs, the gene, and isoform level expression data. There are currently 20,000 users. Next steps for the GTEx project are to be able to look at trans-eQTLs and interactions across chromosomes, as well as conditional eQTLs such as sex, age and clinical variables. Tissue specificity is of considerable interest, both to define relatedness and ubiquity in specificity, for expression and eQTLs. GTEx and ENCODE are working together to integrate with other big genetic datasets, and have established four-donor overlap. A single cell analysis pilot study is ongoing to look at whether the bank samples can be used for single cell analyses. Also, more analyses of the data by the community outside the consortium is expected; the GTEx project will hold a community meeting annually, this year it was held in California, to encourage use of the data. 

    Dr. Ardlie ended her presentation by acknowledging the GTEx Consortium, the GTEx Analysis Working Group, NIH staff, and the donors and their families. She also thanked her team at Broad for data production and analysis, the GTEx Portal team, and the Genemics Platform. 

    NIDA Council members thanked Dr. Ardlie for her presentation. Multiple comments were made including, how useful the GTEx database and tissue databank will be. One of the questions raised was about the issue of diversity of the samples, and the potential to increase disparity since there will be increased knowledge about one major population and not others. Dr. Ardlie spoke about spearheading upcoming efforts with colleagues from Europe and Israel to hold a meeting in Barcelona with international community representatives to add data that is representative of other ethnic groups, environmental exposures, and geographic locations. In addition, there are two groups applying for funding to add perturbations, such as diseases, and age cohorts. Other comments applied to specific tissue types that can be obtained from either the brain bank or GTEx database. 

  5. New AIDS Research Priorities - Robert W. Eisinger, Ph.D., Acting Associate Director for AIDS Research, Acting Director, Office of AIDS Research, NIH 

    Dr. Eisinger began his presentation by stating that NIH supports a comprehensive program of biomedical, behavioral and social science research on HIV and its associated coinfections, complications, and other comorbidities. The goal of his presentation was to focus on the new NIH AIDS research priorities, as well as the several new processes that have been implemented to ensure that resources are available for the highest priorities in HIV/AIDS research 

    Recent scientific advances in the area of HIV pathogenesis, immune dysfunction, and viral reservoirs have led to an unprecedented series of opportunities to develop an AIDS vaccine, to look at new and innovative strategies for a cure for HIV and AIDS, and ultimately an end to the AIDS pandemic. This requires a closer look at how NIH expends its resources for HIV/AIDS research. As part of the transition for the Office of AIDS Research and to ensure AIDS research advances, the NIH has implemented several processes. First, preparing OAR for the future, as its role will be even more important than ever in this intense push to end the epidemic, develop an AIDS cure, and achieve and AIDS-free generation. Dr. Tabak established and chairs a small working group of IC Extramural and Intramural leadership to address the scientific and programmatic role of OAR; and a vigorous national and international search was launched on July 31 for a new OAR Director; search committee co-chairs are Drs. Briggs and Rodgers. 

    On August 12, 2015, Dr. Collins issued a Director’s Statement, which identified the new overarching priorities for HIV/AIDS research at the NIH for the next three to five years. They are: 1) Reduced incidence, including vaccines; 2) Next generation of HIV therapies with better safety and ease of use; 3) Research toward a cure; and 4) HIV-associated comorbidities and co-infections. Cross cutting areas include basic research, health disparities, and training. NIH also issued a notice in the NIH Guide (NOT-OD-15-137), which provided and highlighted these new overarching priorities, as well as a new set of guidelines for determining how AIDS funding would be spent at the NIH. These guidelines assign a high, medium, and low priority for the use of AIDS funds; and were developed based on a report from the OAR Advisory Council’s special working group, looking at a portfolio review. The guidelines were impacted and directed by NIH Leadership, and also informed by the fiscal year 2015 Trans-NIH Plan for HIV-Related Research, which involves hundreds of researchers and scientists, as well as community constituency groups from a wide range of scientific foundations and other organizations. 

    Dr. Eisinger emphasized that the new guidelines are to be used only for determining the use of AIDS funds. They are not used to determine the scientific or technical merit of grants, contracts, and/or intramural projects. The Notice was published in the NIH Guide on August 12 to inform the scientific community of these new standards. The guidelines also contained a schematic on how to fund projects that may contain both an AIDS and a non-AIDS component; the guidelines are designed to be used in standardizing pro-rating levels of support for projects across the different institutes and centers. 

    He then went on to further define high, medium and low priority research areas. The first high priority research area is reducing incidence of HIV/AIDS, which involves the development and testing of potential vaccine candidates, microbicide compounds, as well as Pre-Exposure Prophylaxis candidates; how to improve adherence to treatment regimens; and prevention strategies to improve HIV testing and entry into treatment. The second high priority research area is the development and evaluation of the next generation of HIV therapies with better safety and ease of use, including: developing and testing HIV treatments that are less toxic, longer acting, have fewer side effects and complications, and are easier to take and adhere to than current regimens. This priority also includes implementation research to ensure initiation of treatment as soon as diagnosis has been made, retention and engagement in these services, and achievement and maintenance of optimal prevention and treatment responses. 

    The third high priority research area is research toward a cure, including: developing novel approaches and strategies to identify and eliminate viral reservoirs that could lead toward a cure or lifelong remission of HIV infection, including studies of viral persistence, latency, reactivation, and eradication. The fourth high priority research area focuses on the prevention and treatment of HIV-associated comorbidities, coinfections, and complications such as: addressing the impact of HIV-associated comorbidities, including TB, malignancies, cardiovascular, neurological, and metabolic complications; and premature aging associated with long-term HIV disease and antiretroviral therapy. Cross-cutting high priority areas are basic research, research to reduce health disparities, and training to conduct high priority AIDS research. 

    He then moved on to medium-priority research areas, where HIV/AIDS is a meaningful component of the project and/or knowledge about HIV is enhanced by the project. Examples include: projects that have people or biological specimens from people who are living with HIV, are exposed to HIV, and/or are at elevated risk for HIV infection as part of a broader sample or as a comparative cohort; or a project that addresses health and social issues clearly linked to HIV (transmission/acquisition, pathogenesis, morbidity and mortality, stigma) and examines them in the context of HIV such as other infectious pathogens and diseases, non-infectious pathogens and diseases, substance use and addiction, and mental health disorders. Medium priority research also includes projects that may involve both SIV or HIV/AIDS outcomes and endpoints, or project results that will advance treatment or prevention, and/or provide the tools and techniques and capacity beneficial to HIV research (including training and infrastructure development). 

    Low priority areas are projects that are no longer aligned with the overarching AIDS research priorities. These are critical areas of science and these areas can continue to be supported by NIH but will not be supported using AIDS funds. These include natural history and epidemiology studies that are entirely focused on a comorbidity and do not have a focus on or inclusion of HIV; or basic virology on pathogens that are co-infecting, but not in the context of HIV infection; and basic immunology studies of general relevance, but not specific to HIV. Other low priority areas include data analysis and systems tools that are not HIV-related, such as genomics studies of little or no relevance to HIV, and studies of behavior, such as sexual activities, drug use activities, or social conditions that have multiple negative outcomes where HIV/AIDS is only one of many outcomes being studies without a focus on how HIV/AIDS is unique in that context. 

    In August 2015, Dr. Collins charged the Acting OAR Director with conducting a portfolio review to assess the extent to which the current AIDS research program is aligned with the new overarching HIV/AIDS research priorities. OAR’s approach was to assess in the evaluation all grants and contracts supported with AIDS dollars in FY 2014 and were eligible to re-compete in FY 2016funding. In addition and unique to this portfolio, investigator-initiated intramural projects funded in FY 2014, reviewed by IC’s Board of Scientific Counselors in FY 15, and awaiting a FY16 funding decision were included in the portfolio review. This review was conducted from August through November 2015 and the results were presented at the NIH Director’s Advisory Council on December 11, 2015. 

    Dr. Eisinger provided and discussed the results of the OAR FY 2014 Portfolio Review. The NIH AIDS research budget totaled $2.98 billion and represented over 5,200 extramural grants, 435 intramural projects, and 68 contracts. The study was limited to only those projects that were re-competing in FY 2016 and thus the scale of the portfolio review was brought down to $435 million, including1207 extramural grants, 56 intramural projects, and 11 contracts. Of the 1207 extramural projects, representing $407.41 million: 832 projects (69%) totaling $300.73 million were rated as high priority; 133 projects (11%) totaling $41.46 million were rated as medium priority; and 242 projects (20%) totaling $65.22 million were rated as low priority. The low priority projects included studies on basic virology and immunology, genomics, infectious pathogens outside of the context of HIV; and training projects with no indication of an AIDS component. 

    The intramural portfolio assessment of the 56 projects, totaling $21.35 million found that 18 projects (32%) totaling $10.07 million were rated as high priority; 12 projects (21%) totaling $4.67 million were rated as medium priority; and 26 projects (47%) totaling $6.60 million were rated as low priority. The low priority projects included studies on: basic research, pathogenesis and treatment of infectious pathogens not in the context of HIV, such as Chlamydia, Cryptococcus, Neisseria gonorrhea, hepatitis viruses, and fungal infections; basic studies on tumor immunology and genetics, T-cell development, autoimmunity and cancer; and evaluation of biological and behavioral effects of drug dependence and treatment with no AIDS component. 

    As a result of the OAR review, the funds associated with the identified low priority projects were moved into the Common High AIDS Relevance Pool, totaling approximately $65 million. All of the institutes and centers were eligible to submit applications for common pool funds. Funds from low priority intramural research projects are allowed to continue to support projects in FY 2016, but will be supported with non-AIDS dollars in FY 2017 and beyond, unless the principal investigator realigns the project to high priority AIDS research. 

    Dr. Eisinger presented the new OAR processes set up in FY 2016: 1) OAR is working with the Center for Scientific Review (CSR) to revise the CSR Referral Guidelines, which may result in a restructuring of the AIDS IRG study sections within CSR. 2) OAR is now reviewing the funding opportunity announcements and requests for proposals to ensure that these are properly aligned with the research priorities to receive AIDS funding. 3) Following FY 2016 Omnibus Bill, OAR in consultation with the NIH Director utilized its 3% transfer authority to transfer AIDS funds between ICs. This will allow moving dollars associated with low priority projects into the common pool, and distributing those funds to support projects that are aligned with the highest priorities. 4) OAR has also implemented a process to review and approve all new and competing renewal projects (grants, contracts and intramural projects) to ensure they are aligned with the highest AIDS priorities. And 5) OAR is using its Discretionary Funds to support only peer reviewed grants, contracts and intramural projects. 

    Beginning in fiscal year 2016, the OAR will review how each institute spends their AIDS dollars as part of its congressional mandate and will work closely with institutes to ensure all projects are aligned with the highest priorities and appropriately coded by Strategic Plan code and SIC code. The FY 2017 Trans-NIH AIDS budget was developed by OAR in consultation with the NIH Director, and OAR provided guidance for development of the IC AIDS budget submissions. Each new, re-competing, and expanded initiative must be aligned to one or more of the overarching AIDS research priorities. 

    In summary, Dr. Eisinger stated that these new steps and processes have been implemented to ensure that resources are available to support the development and testing of AIDS vaccine candidates, strategies to achieve a cure, and ultimately, end the AIDS pandemic and hopefully achieve an AIDS-free generation. 

    Dr. Volkow and Council members thanked Dr. Eisinger for his presentation. Comments were raised to help with clarification of the terms comorbidity and co-infections, as research solely on hepatitis C (HCV) or substance use, may not qualify under the high priority AIDS areas. Dr. Eisinger reassured council members that the research needs to have project aims and primary outcomes strictly related to HIV/AIDS to be categorized as high priority; however, this is not to say that research that is not specific to HIV is unimportant or will not be supported. NIH’s budget for non-AIDS research will support meritorious projects that may have a secondary relation to HIV. 

  6. Points to Consider Regarding Tobacco Industry Funding of NIDA Applicants: A Proposed Refresh and Update - Laura Bierut, M.D., NACDA Council Member, Professor, Department of Psychiatry Washington University School of Medicine 

    Dr. Bierut began her presentation with background and history on the Points to Consider Regarding Tobacco Industry Funding of NIDA Applicants document posted on the NIDA website. The document originally addressed NACDA concerns that the interests of the tobacco industry were fundamentally incompatible with the scientific goals and public health mission of NIDA. Given that tobacco companies continue to fund scientific research within academic institutions and other organizations, the document provided points to consider for NIDA and its grantees regarding applications from grantees that also receive support from the tobacco industry. 

    The current landscape of tobacco products is different compared to just a few years ago with the development of Electronic Nicotine Delivery Systems (ENDS or electronic cigarettes). ENDS may provide a less harmful alternative to tobacco smoking; increase tobacco cessation by having greater uptake than traditional Nicotine Replacement Therapy (NRT); inhibit tobacco cessation through dual use with combustible cigarettes; and/or expose nonsmokers, especially youth, to nicotine and potentially increase their likelihood of using other tobacco products. All of the above listed raise important research questions that need to be answered. 

    Thus, a NACDA Workgroup was developed to review the document and recommend updates to it. The proposed revisions allow flexibility for NIDA when considering applications addressing important public health questions related to ENDS and other products: 1) Some current “harm reduction” products that may aid smoking cessation are also tobacco industry products; 2) E-cigarette products and companies are complex, with some only targeting adult smokers, while others may market to youth and non-smokers; 3) The updates are general enough to address any new products on the horizon; 4) NIDA continues to have the flexibility to review each application on a case by case basis; and 5) Grantees who are considering support from e-cigarette or other tobacco companies should discuss their application with NIDA. The purpose of this last point is not to inhibit research in an area that has the potential for good, but instead that there should be consultation with potential grantees. 

    Dr. Bierut thanked other members of the workgroup, including another NACDA member, Dr. Andorn, former council members, and NIDA staff for all of their guidance and help in putting this updated document altogether. She then opened the floor up for discussion. 

    Dr. Volkow and Council thanked Dr. Bierut for her efforts and commended the use of flexibility and keeping the research moving forward in the document. Motion to accept the changes were made. 

  7. Concept Clearances - NIDA Staff

    Eight total concepts received Council clearance. Three were presented by the SBIR Program. 

    Dr. Elena Koustova, Director of the Office of Translational Initiatives and Program Innovations (OTTIPI) presented a concept entitled “Entrepreneurial Training for Addiction Researchers.” The purpose of this FOA is to solicit applications to develop a highly specialized curriculum/training course in biomedical innovation and entrepreneurship that prepares NIDA research force to extend their focus beyond the laboratory and broadens the impact of basic research projects. While knowledge gained from NIDA-supported basic research frequently advances the field of addiction science, some results also show immediate potential for broader applicability and impact in the commercial and public health realms. The sought curriculum will be designed to teach interested basic scientists to recognize this potential. The requested FOA budget is expected to be used, among other expenses, to defray participant costs, enabling participation of NIDA-supported academic institutions where a culture of entrepreneurship is not prioritized. This is the first initiative focused on academic researchers with ideas and technologies that have not yet led to the formation of a startup or have been licensed by an existing company. The initiative will help to stimulate and support those NIDA scientists who would not initially think their ideas and research projects are of entrepreneurial/product development merit; to accelerate the translation of biomedical research to the marketplace and to eventually feed the NIDA Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. 

    Dr. Steve Grant, presented “Improved Technologies and Ligands for Non-invasive Brain Imaging” concept. The proposed SBIR/STTR concept will support small business efforts that address challenges in the above realm including: 1) the further development or commercialization of in vivo imaging technologies, 2) the development of imaging strategies or ligands to enable visualization of latent or replicating virus in the brain, 3) the development of imaging ligands for visualizing changes in receptors or other brain proteins relevant to substance abuse or co-occurring psychiatric disorders, 4) the development of imaging ligands for visualizing neuronal and glial signaling molecules. In addition, development of non-invasive imaging tools will assist medical centers with the need for assaying signaling efficacy or latent/replicating viruses in the brain and pharmaceutical companies involved in treatment development. 

    Dr. Irina Sazanova presented the final SBIR concept “Laboratory and Diagnostic Tools to Advance Microbiome-Brain Research”. The purpose of this FOA is to provide the opportunity for small business companies and encourage them to develop: 1) New or improved technologies to advance microbiome research; 2) New diagnostics tools or assays for fast microbiome analysis; and 3) Databases or computational tools for microbiome, metagenome, and metabolome elements correlatively with CNS diseases. This FOA will enable the development of novel analytical tools, technologies and research resources. The developed tools/resources will facilitate microbiome research and enable researchers to understand the association of the human microbiome with brain and addictive diseases. The studies will justify the therapeutic utility of the microbiome modulation and will lead to novel approaches to cure emotional and gastrointestinal outcomes in SUDs. 

    The remaining five concepts were from the HIV/AIDS program. 

    Dr. Shoshana Kahana presented “Optimizing the HIV Care Continuum for Substance Abuse Populations Living with HIV.” This concept seeks to capitalize on these lessons and calls for applications that focus on optimizing the HIV care continuum, in particular trials that examine the feasibility of integrating and/or optimizing multiple components of the care continuum, such as 

    HIV identification status, linkage and retention in care, and viral suppression for individuals with SUD and HIV. The inclusion of ongoing substance use screening and treatment, as appropriate, as well as the provision of behavioral and biomedical approaches are encouraged. Furthermore, in addition to patient level outcomes, and in order to focus on the larger contexts of vulnerable populations, we strongly encourage applications that include an examination of social and/or more macro-level variables, such as health care provider (clinician, provider, case manager) practices and attitudes, system or organizational capacities, or local policies as they relate to adequate access to substance use and/or HIV care (e.g., harm reduction, opioid substitution therapy, and needle–syringe and condom distribution programs) and their interaction with HIV care continuum outcomes are encouraged. 

    Dr. Yu Lin presented “Implication of Cholinergic Regulation of Immune Function in HIV Infectivity and Pathogenesis.” NIDA seeks to encourage research studying how chronic tobacco smoking affects immune function and its impact on HIV infectivity, pathogenesis and comorbidity. Responsive studies will assess cholinergic capacities, cholinergic anti-inflammatory properties and cholinergic function as associated with host immune status and neurocognitive strength in smokers vs. non-smokers with HIV. The research will inform strategies for developing immunotherapy and comorbidity treatment approaches, possibly contributing to a functional cure of HIV infection. 

    Dr. Richard Jenkins presented “Mobilizing Seek, Test, Treat and Retain Approaches in Rural Opioid Drug Use Epidemics.” This concept would research projects that incorporate rapid epidemiologic and policy assessment, implementation of new or modified services in response to these assessments and evaluation of the initial efficacy of these new or modified services. The rapid assessments of local epidemiology would address drug use and its infectious disease consequences, as well as assessment of local infrastructure and policy that may facilitate or inhibit program and service improvements. These assessments would engage stakeholders and provide foundations for community based programs to prevent new opioid use and facilitate screening and entry into treatment for opioid use and its consequences such as HCV and HIV, as well as interventions to reduce infectious disease transmission such as syringe services. The initial efficacy of these services will be evaluated, along with factors related to successful implementation, and factors related to sustainability such as cost. We plan to engage HRSA, CDC, SAMHSA, and the Appalachian Regional Commission as partners for these projects, and these agencies already have expressed interest. Individual projects will be expected to leverage resources related to existing funding from these federal agencies. 

    Dr. Jag Khalsa presented “Coordination Center for the HIV/AIDS and Substance Use Cohorts Program.” NIDA has funded nine cohorts of diverse substance using populations (MSMs, IDUs, Cocaine) with HIV/AIDS and co-infections that could serve as platforms for supporting innovative research in collaboration with researchers from many disciplines. A wide range of research data on HIV/AIDS and drug abuse associated behavioral, clinical, immunologic, virologic, medical/health consequences (co-morbidities involving cardiovascular, renal, hepatic, neurologic and others) and well characterized specimens have been collected that reside in individual databases. NIDA-funded Avant-Garde awardees and cohort directors/researchers identified the need for better integration and support access to biospecimens and this massive multidisciplinary data to facilitate and support collaborations among and between extramural researchers. Thus, a coordinating center (CC) is needed to optimize research on basic HIV/AIDS and clinical research in substance abusing individuals, e.g., co-morbidities, co-infections. The CC will manage and coordinate all data collections across NIDA-funded U01 sites, facilitate the collaboration between and among the NIDA-funded U01 cohorts, establish a virtual repository for the local bio-specimen repositories, and enable a system to make these data available to the extramural research community. 

    Dr. Vishnudutt Purohit presented “Mechanisms of Immune Activation and Inflammation in Drug-Abusing HIV-Infected Patients on ART.” Despite long-term antiretroviral therapy (ART), low level of viral replication persists in HIV reservoirs contributing to sustained systemic immune activation and inflammation in HIV-infected patients. Chronic inflammation has potential to attenuate the efficacy of ART and promote pathological conditions in HIV patients. Indeed in HIV patients on long-term ART, inflammation has been linked to thrombosis, muscle wasting, neurocognitive impairment, cardiovascular diseases, and obesity. Drugs of abuse have potential to further increase the severity of inflammation in HIV patients on ART. For example, cigarette and marijuana smoking are linked to pulmonary inflammation. Opioid-induced disruption of gut homeostasis and subsequent microbial translocation trigger systemic immune activation and inflammation. Cocaine and methamphetamine abuse are associated with systemic increases in levels of inflammatory markers. NIDA seeks to encourage and support research investigating the underlying mechanisms by which drugs of abuse exacerbate HIV-associated immune activation and inflammation. Results from these studies may help discover therapeutic interventions for improving ART efficacy as well as attenuating chronic inflammation-associated comorbidities in HIV-infected drug-abusing populations. 

  8. There were no Public Comments

  9. Adjourn

    The 122nd meeting of the National Advisory Council on Drug Abuse was adjourned at 3:55 p.m. 


I hereby certify that the foregoing minutes are accurate and complete.

Nora D. Volkow, M.D.
Director, NIDA
National Advisory Council on Drug Abuse
Susan Weiss, Ph.D.
Executive Secretary
National Advisory Council on Drug Abuse

Note: Informational materials provided to the public at the open session of the meeting may be obtained from the Executive Secretary.