Minutes of the 98th Meeting of the National Advisory Council on Drug Abuse

February 5-6, 2008

The National Advisory Council on Drug Abuse convened its 98th meeting at 2:00 p.m. on February 5, 2008 in Conference Room C, 6001 Executive Boulevard, Bethesda, Maryland. Dr. Nora D. Volkow, Director of NIDA, chaired the overall meeting and Dr. Timothy P. Condon, Deputy Director of NIDA, chaired the review of applications. The closed portion of the meeting on February 5, 2008, from 2:00 p.m. until 4:00 p.m., was for the purpose of reviewing applications for Federal grant assistance and was open only to Council members and Federal employees. The open session, which was open to the public, was February 6, 2008, from 8:30 a.m. until 1:00 p.m. The Council adjourned on February 6, 2008 at 1:00 p.m.

Council Members Present:

Louis E. Baxter, M.D.
Warren K. Bickel, Ph.D.
Steve Brasington, M.D. (Ex officio) 
Debra K. DePrato, M.D.
Mark T. Greenberg, Ph.D.
Barry M. Lester, Ph.D.
Daniele Piomelli, Ph.D.
John P. Rice, Ph.D.
Mary Jane Rotheram-Borus, Ph.D.
Ellie Schoenbaum, M.D.
Marina E. Wolf, Ph.D.
Xiaoyan Zhang, Ph.D.

Council Members Absent:

Igor Grant, M.D.
Janet Wood, MBA

Council Chairs Present:

Nora D. Volkow, M.D.
Timothy Condon, Ph.D.

Executive Secretary:

Teresa Levitin, Ph.D.

Federal Employees Present:

Members of the Public Present:

Virginia Anthony - American Academy of Child and Adolescent Psychiatry
Andrea Browning - Society for Research in Child Development
Sue Camaione - MasiMax Resources, Inc.
Tracy Connor, J.D., M.S.W. - Institute for the Advancement of Social Work Research (IASWR)
William Corrigall, Ph.D.
Jessica Cotto, M.P.H.
Susan David
Amy DeYoung - American Academy of Child and Adolescent Psychiatry
Diane Galloway, Ph.D. - Community Anti-Drug Coalition of America
Stacia Hall - American Academy of Child and Adolescent Psychiatry
Marian Kratage - MasiMax Resources, Inc.
Meghan McGowan
Eileen McGrath, J.D. - American Society of Addiction Medicine
Alan Moghul, Ph.D. - National Association of State Alcohol/Drug Abuse Directors (NASADAD)
Geoff Mumford, Ph.D. - American Psychological Association
Amy Pollick, Ph.D. - Association for Psychological Science
Pamela Pressley - Consortium of Social Science Associations
Beth Ray, M.S.
Diedre Watkins - MasiMax Resources, Inc.
Sis Wenger - National Association for Children of Alcoholics

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. Timothy Condon, Deputy Director, NIDA, called the meeting to order and welcomed the Council and staff. Dr. Condon provided an overview of the agenda for the meeting and 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. Teresa Levitin, 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 Office of Science Policy and Communications; the Division of Basic Neuroscience and Behavioral Research; the Division of Clinical Neuroscience and Behavioral Research; the Division of Epidemiology, Services and Prevention Research; and the Division of Pharmacotherapies and Medical Consequences of Drug Abuse presented their applications for consideration by the Council. For each, Council provided concurrence with the initial scientific reviews en bloc.

   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.

   For this Council, 784 applications, requesting $810,321,528 in Total Years Direct Costs, went to review. Of these, 339 were scored by the Scientific Review Groups (SRGs) representing $78,368,190 in First Year Direct Costs and $342,695,527 Total Years Direct Costs. Council concurred with the SRGs in time and amount.

1. Call to Order

   Dr. Nora Volkow, Director, NIDA, called the open portion of the meeting to order and welcomed the Council members. She 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. Dr. Volkow called attention to future Council meetings: May 13-14, 2008, September 9-10, 2008; February 3-4, 2009, May 12-13, 2009, September 15-16, 2009; February 2-3, 2010, May 4-5, 2010, September 14-15, 2010.

2. Consideration of the Minutes of Council

   The Minutes of the September 2007 meeting were approved as written.

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

   Dr. Volkow began her report with a budget update, noting that the actual 2006 budget represented a 0.8% decrease over the prior year and that both the 2008 estimated and 2009 President's budget would yield an increase of 0.1%.

   In describing what is new at NIH, Dr. Volkow presented several research initiatives in the epigenetics of human health and disease. She then identified four NIDA-proposed new Roadmap initiatives and noted the activities for which NIDA has primary responsibility. She also described the process by which Roadmap initiatives are established.

   Dr. Volkow noted that NIDA mourns the passing of Dr. William Pollin, NIDA's Director from 1975 to 1985. Dr. Pollin was a noted psychiatrist who passed away at the age of 85. She then welcomed Mary Affeldt as the new Associate Director for Management and Executive Officer of NIDA.

   One recent NIDA activity has been the development of a Draft Strategic Plan, which outlines four major goal areas of prevention, treatment, HIV/AIDS and cross cutting priorities. NIDA has invited comments on this plan and has identified strategic objectives for each goal area to guide NIDA's research agenda for the future. Also, NIDA will be moving its fellowship applications to CSR for review as of the April 2008 receipt date. Dr. Volkow noted that fellowship applications from most Institutes are currently reviewed at CSR and that additional information about this change will be posted on the NIDA web, along with a Q&A section.

   Dr. Volkow then turned to activities within NIDA, noting the publication of the 2008 Avant-Garde Award Program for HIV/AIDS research, which will be a 5-year $2.5M award designed to support individual scientists of exceptional creativity who propose cutting-edge and transformative approaches to major challenges in biomedical and behavioral research on drug abuse and HIV/AIDS.

   Under work associated with the Division of Basic Neurosciences and Behavioral Research, Dr. Volkow introduced the Neuroscience Information Framework, a resource registry and concept based query system to enhance neuroscience research by enabling discovery and access to research data and tools worldwide. Dr. Volkow noted the major investigators involved in this project. She described the services that NIFv1.0 provides, including a means to register and query web resources across biological scales and an interface for searching across multiple types of resources with a single query. The many advantages of this registry were identified.

   The Division of Epidemiology, Services and Prevention Research continues to support the Monitoring the Future Study from the University of Michigan, and this study has shown a 24% decline from 2001 to 2007 in the percent of students reporting past month use of any illicit drug. President Bush held a press conference highlighting the importance of these results. Data demonstrating that adolescents who exercise regularly had lower prevalence rates of legal and illegal drug use were also presented, as were findings about nicotine use and prescription medication, and Dr. Volkow described the importance of NIDA working with other Institutes to create clinical trials studying substance abuse and diabetes or obesity in children and adolescents as well as the importance of identifying the effects of brief interventions in primary care settings.

   The Center for the Clinical Trials Network is proposing to study exercise as a treatment for substance use disorders to see if physical activity alone has an effect on factors such as relapse. The Division of Clinical Neurosciences and Behavioral Research has released an RFA on facilitating self-control of substance abuse related brain activity through real-time monitoring of fMRI signals. The Division of Pharmacotherapies and Medical Consequences of Drug Abuse held a medications development scientific workgroup meeting last November to elicit views on a number of clinical trials contracts under consideration, and NIDA will pursue development of a cocaine vaccine and conduct a clinical trial to help prevent relapse during treatment of cocaine abusers.

   Dr. Volkow then presented information on other recent NIDA activities including the very successful Drug Facts Chat Day that gave students throughout the country the opportunity to ask questions. More than 36,000 questions from students were submitted, far more than anticipated. A Congressional briefing sponsored by the Friends of NIDA was held in November; the topic was treating nicotine and tobacco dependence: the science of quitting. In January the Institute of Medicine held a forum on neuroscience and nervous system disorders and Dr. Volkow spoke on "The Ultimate Challenge; Integrating Function Across Levels of Analysis". NIDA staff organized a short, intensive course on the genetics and epigenetics of addiction that was very successful. Staff also organized a mini-convention on frontiers in addiction research at the Society for Neuroscience's annual meeting, where outstanding scientists presented recent findings and discussed future directions in the neurobiology of drug abuse and addiction. NIDA will convene a Blending Addiction Science and Treatment Conference in June to assess the impact of evidence-based practices on individuals, families and communities. This is an opportunity for scientists and people providing treatment in community treatment programs to learn from each other. Also, at the XVII International AIDS Conference in Mexico City in August, NIDA will sponsor a skills-building workshop and a satellite symposium in order to build networks and opportunities for new research. Dr. Volkow concluded by noting the importance of ensuring that innovative research be identified and supported.

   Council thanked Dr. Volkow for her report, and there was then discussion about ways to use technology to bring more of the science of substance abuse to the public, e.g., information for iPods and various web sites; about the importance of Council feedback on the Strategic Plan; about the possible role of exercise, sensory experience, and team sport participation on drug abuse; about the quality of predictive animal models; about the role of volitional control; about the need for more human laboratory models; about partnering with NIDDK to study eating behaviors, particularly in obese and diabetic children and adolescents, to see if there are common elements in the use of drugs and food; about the possible relationship between gastric surgery for obese children and subsequent substance abuse; about the need for more developmental models; about the importance of the environment and structural factors in prevention; about the need to understand both genetics and environment; about the response to Chat Day and the importance of identifying networks and ways to reach children and adults on a regular basis; about possibly developing links with MTV and BET, given the ties of children and adolescents to these media; about the role of physical activity and treatment as well as prevention; about the epidemiology and growth of prescription drug misuse and about the complexity of information access and maintenance of the quality of information.

4. Strategies to Identify and Increase Innovative Research - Alan Krensky, M.D., Deputy Director, NIH and Director, Office of Portfolio Analysis and Strategic Initiatives (OPASI), OD, NIH On Peer Revi

   Dr. Alan M. Krensky, Director of the Office of Portfolio Analysis and Strategic Initiatives (OPASI) and Deputy Director, NIH, began his presentation by noting that the NIH Office of the Director sponsors several new programs designed to foster innovation, including the Pioneer Award, the New Innovators Award and Roadmap grand challenges, which include interdisciplinary research teams attacking important questions and the CTSAs, which present a new approach to translational research by transforming the way academic institutions do translational and clinical research.

   He pointed our that there is also a High-Risk/High-Reward Demonstration Oversight Group mandated by the 2006 NIH Reform Act that is charged with defining the NIH portfolio, recommending strategic initiatives, and evaluating high-risk/high-reward science at NIH. A report will be prepared for Congress in 2009.

   Dr. Krensky then summarized the ideas of the "Fostering Innovation" workshop sponsored by OPASI in December of 2007 that addressed approaches to identify and increase innovative research. This conference, chaired by Dr. Krensky and Dr. Keith Yamamoto of UCSF, brought in over a dozen senior scientists to discuss how to enhance innovation at NIH. Dr. Krensky noted the distinction between innovation and transformation, with innovative research being original, inventive, paradigm-shifting research, while transformative research is revolutionary, disruptive, paradigm-generating research. There are, however, he noted, many factors that discourage innovation, including the NIH grants process and the expansion of soft money positions during the doubling of the NIH budget, with the current flattening of the budget encouraging conservatism in both applicants and reviewers.

   There are also environments in which innovation thrives, and Dr. Krensky pointed to the importance of research institutions in fostering innovation through supporting investigator's salaries with "hard" money and focusing on intellectual endeavors of faculty rather than on grant acquisition.

   Dr. Krensky then presented the top ten recommendations of the workshop participants and elaborated on each. These recommendations are, in the order of importance determined by the group, as follows: 1) separate grant mechanism based upon track record so that more weight is given to the track record of the individual; 2) increase career awards and free up the investigator to do more risky work; 3) create a separate mechanism for "transformative" research, perhaps using a very small portion of the NIH budget for such work; 4) foster new ideas outside the mainstream, perhaps with another review mechanism; 5) recruit generalists to review applications; 6) separate salaries from research grants; 7) provide awards for career years three through nine, an important period of transition; 8) reform intramural NIH to focus more on high risk research; 9) promote local environments that encourage risk taking; 10) fill the gap between basic discovery and commercialization.

   Dr. Krensky concluded by noting that a healthy ecosystem requires better alignment and cooperation among government, academia, philanthropy and industry and pointed out that this could include severing direct ties between research grants and salary, encouraging excellent scientists to take leadership roles, and encouraging risk-taking by providing more pilot grants and bridge grants for years three to nine of a scientist's research career. He noted that philanthropy has the opportunity to fill in the space between government, academia and industry.

   Council members thanked Dr. Krensky for his presentation, and there was then discussion about the iron triangle of academia, government and industry, including the role of SBIR/STTR research, culture change in academia, public-private partnerships, ways to go from basic science to cures, the role of the CTSA, leveraging examples, the growing importance of working with philanthropists, ways of thinking about salaries for faculty, how research is supported in Europe, and the use of overhead funds. Dr. Krensky concluded by noting again how complex these issues are, how the entire ecosystem of research needs to be considered, and how it is important to be flexible in approaching these complex issues, since there will not be "one-size fits all" solutions.

5. Mentored Career Development (K) Award Outcomes - Cindy Miner, Ph.D., Deputy Director, Office of Science Policy & Communications, NIDA

   Dr. Lucinda (Cindy) Miner began her presentation by noting that she would be responding to a number of questions that had been raised by Council and were part of the new NIDA Dashboard. She briefly described the characteristics of a Mentored Career Award and noted the types of Mentored Career Awards that NIDA supports. She then pointed to the significant growth of these awards from FY 1992-2006, particularly noting the leadership of Dr. Timothy Condon, who recognized the potential of these types of awards. NIDA has gone from a handful of awards in the early 1990s to over 140 current Mentored K awards in the current portfolio.

   Dr. Miner showed the breakdown of mentored K awardees by degree, their current research involvement, their subsequent funding activity, further divided by clinical or preclinical research. The data indicate substantial success in terms of funding and publications, with, for example, 100% of the M.D./Ph.D. and 90% of the Ph.D. recipients of the Mentored K actively publishing. Further, of those with basic research interests, 80% reported submitting applications and 49% were funded, while for the patient oriented researchers, there was a 100% rate of submitting applications and 44% have been funded. And most of those who have been funded have been funded by NIDA, another indicator of the success of the Mentored K program.

   Dr. Miner also described the career trajectories of several of the M.D., Ph.D., and M.D./Ph.D. recipients of Mentored K awards, noting the individual patterns of accomplishment and explaining the different paths that had been taken.

   She then turned to the K12 program, noting that the purposes of the K12 award to the American Academy of Child and Adolescent Psychiatry (AACAP) for the Physician Scientist Program in Substance Abuse were to increase the number of child psychiatrists carrying out drug abuse research and to increase the visibility and presence of drug abuse research in child psychiatry. Prior to the establishment of this program, there was only one child psychiatrist grantee. The program was established in January of 1998, with seven scholars participating in the first cohort (1998-2003) and five in the second (2005-2009). Dr. Miner showed the grant funding histories for both groups, noting that, thus far, the first cohort had obtained 20 grants on which the K12 scholar was a principal investigator and 27 on which the scholars were co-investigators, while the second cohort had already received two grants. She pointed to the 200 publications of the first cohort and 16 publications of the second cohort and noted other indicators of the success of this program, such as the substantial increase in the number of substance abuse related research presentations at the AACAP annual meeting and the participation of K12 scholars in the AACAP annual meeting. Dr. Miner noted that the data clearly demonstrate that this has been -- and continues to be -- a very successful program.

   Dr. Miner than presented additional analyses of the Mentored K program, noting how clinical and preclinical investigators compare in terms of success and identifying success rates by degree, i.e., M.D., Ph.D./O.D. or M.D./Ph.D.

   To respond to previous Council questions about success rates for new and competing continuation applications as well as success rates for original and amended applications, Dr. Miner prepared slides with comparisons between NIDA and NIH as well as success rates over time for new investigators and others for original and amended applications.

   Council thanked Dr. Miner for her presentation. Subsequent discussion included comments about the resources needed for M.D.s and clinical researchers to be competitive, the outcomes of clinicians participating in a K program at a Council member's institution, and the role of universities in supporting research.

6. Relapse to Food Seeking: Role of CRF, Peptide YY3-36, and Orexin - Yavin Shaham, Ph.D., Behavioral Neuroscience Branch, Intramural Research Program, NIDA

   Dr. Yavin Shaham of the NIDA Intramural Research Program provided an overview of ongoing research projects in his laboratory in the Neurobiology of Relapse Section of the Behavioral Neuroscience Branch. These projects include context-induced reinstatement of heroin seeking, incubation of cocaine craving, incubation of conditioned fear, and, the project that was the focus of his presentation, relapse to food seeking.

   Dr. Shaham presented a brief description of a reinstatement model, an animal model of relapse to drug-taking behavior, and noted the adaptation of the reinstatement model to study 1) the role of CRF in reinstatement of food seeking induced by both a pharmacological stressor (yohimbine) and acute re-exposure to food pellets (pellet priming) and 2) the effect of PYY3-36 and the hypocretin 1 receptor antagonist SB334867 on reinstatement induced by yohimbine, pellet priming and cue (a tone-light cue previously paired with pellet delivery).

   After describing further the reinstatement model of drug relapse and noting the increase in interest in reinstatement work, Dr. Shaham presented the results of several studies and projects. Study 1 focused on the role of CRF in reinstatement of food seeking induced by the pharmacological stressor of yohimbine. Dr. Shaham noted that stress can provoke relapse to unhealthy eating habits and that humans are particularly vulnerable to this effect when dieting. However, this issue has not been explored in preclinical laboratory studies. Dr. Shaham explained why what is currently known about yohimbine and CRF might provide a way to explore this issue. Dr. Shaham found that the CRF1 receptor antagonist antalarmin decreases yohimbine-induced reinstatement of food seeking, that antalarmin decreases yohimbine-induced reinstatement of alcohol seeking and that the CRF1 antagonist antalarmin reverses yohimbine's effects on social and "antisocial" behaviors in the experimental rats. Thus, Dr. Shaham concluded that, as in the case of drug relapse, the reinstatement model can be used to study mechanisms underlying relapse to maladaptive eating habits and that the effect of antalarmin on yohimbine-induced reinstatement of food and alcohol seeking is likely mediated by extrahypothalamic CRF1 receptors.

   Dr. Shaham then presented two projects: the effect of PYY3-36 on yohimbine-, pellet-priming and cue induced reinstatement of high fat food seeking and the effect of the hypocretin 1 receptor antagonist SB 334867 on high-fat food self-administration and relapse to food seeking in rats. He summarized conclusions from both projects and then noted the implications of the findings. His data suggest 1) dissociation between the neuronal mechanisms mediating stress-induced relapse to food seeking versus food priming- or cue-induced relapse and 2) potential dissociation between the neuronal mechanisms mediating food self-administration versus food priming- or cue-induced relapse. He then noted the clinical implications of this work: 1) CRF1 receptor antagonists should be considered as pharmacological adjuncts in dietary treatments of maladaptive or excessive eating habits; 2) PYY3-36 may be a more effective treatment for relapse prevention than for decreasing ongoing high-fat food intake; and 3) Hypocretin 1 receptor antagonists may be a more effective treatment for decreasing ongoing high-fat food intake than for relapse prevention.

   Council members thanked Dr. Shaham for his presentation and asked if he had had the opportunity to look at strain differences or genetic influences. Dr. Shaham answered that he has not yet had time to do so.

   Council Operating Procedures And Statement of Understanding - Teresa Levitin, Ph.D., Director, Office of Extramural Affairs, NIDA

   Dr. Levitin reminded the Council members that, on a yearly basis, they need to review and approve of the Council Operating Procedures and Statement of Understanding. Dr. Levitin noted that the current statement had already been sent to them and that, thus far, she had received no requests for changes in the delegation of authority or any other matter. As no questions or comments were raised, Dr. Levitin asked for approval, and the Council unanimously voted to approve the document as written.

7. Public Comments

   Prior to opening the session for public comments, Dr. Volkow reported that there had been an attack on Dr. Edith London's home in California. It is believed that this is the work of terrorists protesting the use of animals in research. Dr. Volkow noted that no one was hurt but that the impact of such an attack must be devastating. She further noted that the NIH will prepare a statement about this and she welcomed any suggestions Council might have to help protect investigators.

   Dr. Virginia Anthony, Executive Director of the American Academy of Child and Adolescent Psychiatry was then invited to present her remarks. She thanked Dr. Volkow for her commitment to children and adolescents and to research about substance abuse in children and adolescents. She also noted the success and importance of the K-12 mechanism.

   Sis Wenger, President of the National Association for Children of Alcoholics, noted that her organization sees itself as the family recovery support advocacy organization and that it will be celebrating its 25th anniversary. She described this organization and some of its activities and called for more work on asking questions that have not already been asked. She also thanked the Council and the NIDA staff for all their work.

8. Adjournment

   The 98th meeting of the National Advisory Council on Drug Abuse was adjourned at l:00 p.m.

Certification

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

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