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Director's Report to the National Advisory Council on Drug Abuse - May, 2003

Program Activities

New NIDA PAs and RFAs

On February 6, 2003, NIDA issued a Request for Applications (RFA) entitled Neuroimaging the Effects of Drugs of Abuse on the Development of the Human Nervous System (RFA-04-002). This RFA is designed to encourage research that takes advantage of the rapidly evolving methodology of neuroimaging to further our understanding of the consequences of drug exposure, abuse and addiction on the developing human brain. Neuroimaging is progressing rapidly and new techniques are continually being developed and refined providing a window into the structural, neurochemical and functional neurobiology of the nervous system. Research that addresses the effects of drug exposure during development, spanning the continuum of development from in utero exposure through the transition to adulthood, is greatly needed. This announcement seeks to encourage investigators experienced in the field of drug abuse, as well as researchers from the spectrum of disciplines that investigate neurobiological and neurobehavioral aspects of typical and atypical development, to apply their knowledge and expertise to the complexities of the effects of drugs of abuse on the developing human brain.

On April 28, 2003, NIDA issued an RFA entitled NIDA Neuroproteomics Research Centers (NIDA NPRCs) (DA-04-004). These Centers should be built around scientific themes that address questions relevant to the mission of NIDA. The Centers will support already existing neuroscience research, provide training in proteomics technologies and develop new proteomics technologies. The objective of this program is to provide technical and administrative support for proteomics Centers in order to increase the accessibility of the Centers to neuroscience researchers at institutions with a demonstrated need for such a resource, to develop new or improve existing proteomics technologies that would be applied to the analysis of tissues of the nervous system and promote sharing of information with the scientific community. Letter of Intent Receipt Date for this RFA is September 24, 2003; Application Receipt Date is October 24, 2003.

PAs and RFAs Issued With Other NIH Components/Agencies

On February 20, 2003, NIDA, in collaboration with a number of other NIH Institutes, the Centers for Disease Control and Prevention (CDC) and the United States Agency for International Development (USAID), issued a Program Announcement (PA) entitled Planning Grants to Organize Programs for International Clinical, Operational, and Health Services Research Training for AIDS and Tuberculosis (PAR-03-073). This PA, which replaces PA-02-022, published in the NIH Guide on November 28, 2001, provides extended support for training to foster collaborative, multidisciplinary research in developing country sites where HIV/AIDS, TB or both are significant problems. This program is an integral and critical component of a comprehensive global strategy of the NIH and Department of Health and Human Services (DHHS) to address the needs of the millions suffering from HIV/AIDS, tuberculosis, and related conditions in resource-limited nations.

On March 27, 2003, NIDA, in collaboration with a number of other NIH components, issued a Program Announcement entitled Centers for AIDS Research: D-CFAR, CFAR (PAR-03-089). This PA, which replaces PAR-00-054, published in the NIH Guide on February 9, 2000, invites applications for center core grants (P30) to support Centers for AIDS Research: standard CFARs (CFAR) and Developmental CFARs (D-CFAR). CFAR cores provide infrastructure and promote basic, clinical, behavioral and translational AIDS research activities at institutions that receive significant AIDS funding from multiple NIH Institutes or Centers. CFARs foster synergy and improve coordination of research, support emerging research opportunities, and promote economy of scale through resources shared by multiple independent laboratories.

On March 31, 2003, NIDA, in collaboration with the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Aging (NIA), and the National Institute of Environmental Health Sciences (NIEHS), issued a Program Announcement entitled Gene Discovery for Complex Neurological and Neurobehavioral Disorders (PAS-03-092). The goal of this PA is to promote the identification of susceptibility genes for complex neurological and neurobehavioral disorders. For this PA, complex disorders are defined as those caused by the interaction of multiple genes, or by a combination of genetic and environmental risk factors. Many of these disorders are relatively common and clinically heterogeneous. Projects focusing on any phase of the gene discovery process, from initial patient ascertainment to positional cloning, are appropriate. Novel approaches, including the use of intermediate phenotypes that potentially underlie complex disorders, are also encouraged.

On April 7, 2003, NIDA, in collaboration with numerous other NIH and DHHS components, issued a Program Announcement entitled Research on Children Exposed to Violence (PAR-03-096). This PA invites grant applications that will enhance our understanding of children exposed to domestic violence, community violence, and war/terrorism. This PA is designed to develop new knowledge in these areas and in the definition, identification, epidemiology, prevention, etiology, effects, early intervention, and mechanisms of violence exposure.

On April 17, 2003, NIDA, in collaboration with numerous other NIH components, issued a Program Announcement entitled Innovations in Biomedical Computational Science and Technology (PAR-03-106). Through this PA, participating Institutes and Centers of NIH invite applications for innovative research in biomedical computational science and technology to promote the progress of biomedical research. As defined here, biomedical computing or biomedical information science and technology includes database design, graphical interfaces, querying approaches, data retrieval, data visualization and manipulation, data integration through the development of integrated analytical tools, and tools for electronic collaboration, as well as computational and mathematical research including the development of structural, functional, integrative, and analytical models and simulations.

On April 18, 2003, NIDA, in collaboration with numerous other NIH components, issued a Program Announcement entitled NIH Small Research Grant Program (R03) (PA-03-108). This announcement redefines the NIH Small Grant (R03) mechanism, and extends its use to investigator-initiated applications at the participating Institutes and Centers. The R03 award supports small research projects that can be carried out in a short period of time with limited resources.

On April 18, 2003, NIDA, in collaboration with numerous other NIH components, issued a Program Announcement entitled NIH Exploratory/Developmental Research Grant Award (R21) (PA-03-107). This announcement redefines the NIH Exploratory/Developmental Research Grant Award (R21) mechanism, and extends its use by participating NIH components as an investigator-initiated mechanism. The R21 is intended to encourage exploratory and developmental research projects by providing support for the early and conceptual stages of these projects.

On February 12, 2003, NIDA, along with a number of other NIH Institutes, issued an RFA entitled Clinical Research Education and Career Development (CRECD) in Minority Institutions (RR-03-007). CRECD awards are intended to support the development and implementation in minority institutions of curriculum-dependent programs to train selected doctoral and postdoctoral candidates in clinical research leading to a Master of Science in Clinical Research or Master of Public Health in a clinically relevant area. A successful program will result in an accredited master's degree program and will produce well-trained clinical researchers who can lead clinical research projects. The Letter of Intent receipt date for this RFA was March 31, 2003; Application Receipt Date was April 29, 2003.

Other Program Activities

Increased Focus on "Relapse Models" within DTR&D's Contract Infrastructure for Medications Discovery
A competitive renewal of NIDA's contract to support behavioral pharmacology studies for the Opiate Treatment Discovery Program was awarded to Virginia Commonwealth University in February of 2003, with increased support for the evaluation of potential medications in heroin self-administration relapse models and decreased support for work in opiate-dependent monkeys. This change reflects a continuing shift of resources toward addressing the relapse prevention aspect of opiate addiction treatment. Within the Cocaine Treatment Discovery Program, a separate contract (also with VCU) supports the evaluation of potential medications in cocaine self-administration relapse models. On April 10, 2003, in San Diego (prior to the Experimental Biology meeting), Drs. David McCann and Jane Acri, both of DTR&D, co-chaired a consultants meeting to review related contract progress and to discuss future directions of these efforts. A highlight of the meeting was the presentation of data - obtained during protocol development efforts - showing a striking interaction between stress and conditioned cues, two triggers to the reinstatement of drug seeking behavior that are usually considered in isolation. The unpublished findings have impacted protocols used for compound evaluations under NIDA's contracts and, when reported to the field, will likely stimulate increased research on the interactions between stress and conditioned cues. VCU contract scientists include Drs. Patrick Beardsley, Keith Shelton, Charlie Cook, and Louis Harris.

Preclinical Methods for Evaluating Compounds with Potential for Treating Methamphetamine-Induced Cognitive Impairment
On April 29, 2003, in Rockville, Dr. Nathan Appel, DTR&D, chaired a consultants meeting entitled, "Preclinical Methods for Evaluating Compounds with Potential for Treating Methamphetamine-Induced Cognitive Impairment." The purpose of the meeting was to review preclinical models of methamphetamine-induced cognitive impairment that NIDA might employ in contract-supported efforts to evaluate potential medications. Dr. Sara Simon discussed how cognitive impairment as a consequence of methamphetamine abuse is manifested in patients and how it has been studied in clinical experiments. NIDA grantees Drs. Victoria Luine, John Marshall, and Charles Voorhees presented their work on the effects of methamphetamine on cognitive impairment in rats. A group of listening consultants, primarily experts on preclinical models of cognitive impairment and drug screening from major pharmaceutical companies and academe provided feedback to NIDA that will help plan and develop a preclinical program to evaluate potential drug candidates for treating methamphetamine-induced cognitive impairment. The meeting organizers were Dr. Appel, Mr. Hirsh Davis, DTR&D, and Dr. Jerry Frankenheim, DNBR.

National Drug Abuse Treatment Clinical Trials Network (CTN) Protocol Update

  • Protocols CTN 0006 and CTN 0007 have closed enrollment. Over 800 patients were randomized across 20 community treatment programs in 9 states.
  • Protocol CTN 0004 (Motivational Enhancement Treatment to Improve Treatment Engagement and Outcome in Subjects Seeking Treatment for Substance Abuse) is actively enrolling at 6 sites across 3 states. A total of 358 participants have enrolled in this study so far.
  • Protocol CTN 0011 (A Feasibility Study of a Telephone Enhancement Procedure - TELE - to Improve Participation in Continuing Care Activities) began enrollment in January 2003. Over 150 patients in two sites have been enrolled in the last three months.
  • Protocol CTN 0008 (Baseline Survey) has been actively collecting survey information in all 17 Nodes since January 2002.
  • Protocol CTN 0009 (Smoking Cessation Treatment With Transdermal Nicotine Replacement Therapy in Substance Abuse Rehabilitation Programs) started enrolling April 9, 2003. This study will be carried out at 12 Community Treatment Programs across 7 Nodes.
  • Protocol CTN 0010 (Buprenorphine/Naloxone Facilitated Rehabilitation for Opioid Dependent Adolescents/Young Adults) and Protocol CTN 0021(Motivational Enhancement Treatment to Improve Treatment Engagement and Outcome for Spanish-Speaking Individuals Seeking Treatment for Substance Abuse) are in the final stages of approval before being launched in the CTN. Enrollment is expected to begin in Second Quarter 2003.
  • Protocol CTN 0012 (Infections Screening in Substance Abuse Treatment Programs) is in the final stages of approval. The protocol training was held at the Albuquerque Steering Committee Meeting in March 2003. The trial is expected to begin in April or May 2003.
  • Protocols in the third wave have been submitted and are in various stages of development and review. Protocol CTN 0013, Motivational Enhancement Therapy to Improve Treatment Utilization and Outcome in Pregnant Substance Abusers, has been approved for implementation. Final IRB approvals are being obtained. Enrollment is expected to start in May or June of 2003. Three HIV protocols (CTN 0017 HIV and HCV Intervention in Drug Treatment Settings, CTN 0018 HIV/STD Safer Sex Skills Groups for Men in Methadone Maintenance or Drug Free Outpatient Programs, and CTN 0019 HIV/STD Safer Sex Skills Groups for Women in Methadone Maintenance or Drug Free Outpatient Programs) were reviewed at the April Data and Safety Monitoring Board (DSMB) Meeting. Protocol CTN 0020, Job Seekers Training for Patients with Drug Dependence, was also reviewed at the April DSMB. These studies are expected to be launched in the summer or fall of 2003.
  • Five new research concepts have been approved for further development into protocols. The protocol teams and Lead Investigators were approved at the Steering Committee Meeting on October 23, 2002. First versions of the protocols are expected July 1, 2003.
  • The CTN Design and Analysis Workgroup and the Dissemination Subcommittee are developing guidance on the implications of releasing data to clinics that participate in CTN clinical trials prior to completion of the trial and publication of the data. While acknowledging the desirability of releasing data to clinics as soon as possible in the process, the document will provide guidance on the minimum standards necessary for protecting the integrity of clinical trials and data analyses, and will address some of the issues surrounding different types of preliminary analyses that a Lead Investigator may perform, and which represent opportunities for early release of data to participating clinics.

Neuroscience Perspectives Tutorial Series
Dr. Herbert Weingartner, DNBR, designed a tutorial series (Neuroscience Perspectives) for all of NIDA staff. The series meets on the first and third Tuesday of each month from 2:00-3:00pm in the NIDA conference room.

NIDA's New and Competing Continuation Grants Awarded Since May 2003

Aharonovich, Efrat -- New York State Psychiatric Institute
Cognitive Deficits: Treatment Outcome In Cocaine Abusers

Aldrich, Jane V. -- University of Kansas Lawrence Affinity Labels for Opioid Receptors

Anagnostaras, Stephan G. -- Emory University
Memory Processes Governing Psychostimulant Sensitization

Andersen, Susan L. -- McLean Hospital
Translational Imaging of Methylphenidate Exposure

Aston-Jones, Gary S. -- University of Pennsylvania
Role of Extended Amygdala In Opiate and Cocaine Abuse

Bannon, Michael J. -- Wayne State University
Cocaine-Binding Dopamine Transporter: Molecular Biology

Bayer, Barbara M. -- Georgetown University
Lymphocyte Activity During Stress: Effects of Morphine

Bennett, Larry W. -- University of Illinois at Chicago
Jane Addams Substance Abuse Research Collaboration

Bergman, Jack -- McLean Hospital, Belmont, MA
Behavioral Effects and Abuse of Dopaminergic Drugs

Borchardt, Ronald T. -- University of Kansas Lawrence
Cyclic Prodrugs of Opioid Peptides

Bracken, Michael B. -- Yale University
Paraxanthine and Reproductive Effects of Caffeine

Broman, Clifford L. -- Michigan State University
Race and Family Factors In Adolescent Drug Use

Brook, Judith S. -- Mount Sinai School of Medicine
Drug Use and Problem Behaviors In Minority Youth

Carr, Kenneth D. -- New York University School of Medicine
CNS Mechanisms That Modulate Reward

Caudle, Robert M. -- University of Florida
Targeted Cholera Toxin for Treatment of Hyperalgesia

Dey, Sudhansu K. -- Vanderbilt University
Endocannabinoid Signaling During Early Pregnancy

Dorn, Lorah D. -- University of Pittsburgh at Pittsburgh
Smoking and Metabolic Complications In Adolescent Girls

Dym, Martin -- Georgetown University
A New Approach To Generate Transgenic Animals

Ettenberg, Aaron -- University of California Santa Barbara
Mechanisms of Opiate and Stimulant Drug Reinforcement

Fleckenstein, Annette E. -- University of Utah
Psychostimulants and Monoamine Transporters

Flynn, Patrick M. -- Texas Christian University
Organizational and Resource Assessments for Treatment Providers

Gabuzda, Dana H. -- Dana-Farber Cancer Institute
Monocyte Viral Reservoirs In HIV-1 Dementia

Gahring, Lorise C. -- University of Utah
Cholinergic Modulation of Inflammatory CNS Cytokines

Gilchrist, Lewayne D. -- University of Washington
Tandem Risk: Outcomes for Children of Teen Mothers

Glennon, Richard A. -- Virginia Commonwealth University
Chemical/Behavioral Studies On Hallucinogenic Agents

Goeders, Nicholas E. -- Louisiana State University Health Sciences Center, Shreveport
Environmental Influences On Cocaine Self-Administration

Goldsamt, Lloyd A. -- National Development & Research Institutes
Behavioral Aspects of HIV/HBV/HCV Risks In New Injectors

Grabowski, John -- University of Texas Health Sciences Center, Houston
Pharmacotherapy For Cocaine Dependence

Grace, Anthony A. -- University of Pittsburgh at Pittsburgh
Stress-Induced Alterations In Amygdala-LC Interactions

Grimm, Jeffrey W. -- Western Washington University
Incubation of Craving: Neural Substrates

Heimer, Robert -- Yale University
Syringe Exchange Based Hepatitis B Vaccination of IDU's

Herzog, Thaddeus A. -- H. Lee Moffitt Cancer Center & Research Institute
Stage Versus Continuum Models For Smoking Cessation

Hjelmstad, Gregory O. -- Ernest Gallo Clinic and Research Center
Plasticity of Kappa Opioid Function In Reward Circuitry

Howells, Richard D. -- University of Medicine and Dentistry of New Jersey, Newark
Purification and Mass Spectrometry of Opioid Receptors

Hruby, Victor J. -- University of Arizona
New Modalities for Treatment of Pain and Drug Abuse

Hser, Yih-Ing -- University of California, Los Angeles
Readiness for Implementation of Research To Practice

Hussey, Jon M. -- University of North Carolina, Chapel Hill
Child Maltreatment and Later Drug Use

Javitch, Jonathan A. -- Columbia University Health Sciences
Dopamine Transporter: Substrate & Cocaine Binding Sites

Kaplan, Howard B. -- Texas A&M University System
Drug Abuse and Other Deviant Adaptations: Two Generations

Kelley, Ann E. -- University of Wisconsin, Madison
Plasticity and Learning In A Corticostriatal Network

Knapp, Pamela E. -- University of Kentucky
Opioids Modulate Oligodendrocyte Development & Function

Koek, Wouter -- University of Texas Health Sciences Center, San Antonio
Neuropharmacology of GHB Discrimination

Largaespada, David A. -- University of Minnesota, Twin Cities
Transposon Mediated Insertional Mutagenesis In Mice

Laudet, Alexandre -- National Development & Research Institutes
12-Step As Aftercare: Predictors and Effectiveness

Lester, Henry A. -- California Institute of Technology
Biogenic Amine Transporters-Structure/Function

Liguori, Anthony -- Wake Forest University Health Sciences
Motivation and Attention In Marijuana Use and Withdrawal

Luthar, Suniya S. -- Columbia University Teachers College
Substance Abuse Among Suburban Youth: Prospective Study

Lysle, Donald T. -- University of North Carolina, Chapel Hill
Opioid-Induced Immune Alterations: Sex Differences

Mackler, Scott A. -- University of Pennsylvania
NAC-1 A Cocaine Regulated mRNA In the Rat Brain

Margolin, Arthur -- Yale University
Spiritual Self-Reevaluation Therapy for HIV+ Drug Users

Markman, Arthur B. -- University of Texas, Austin
Effects of Goal Activation on Competing Goals

Matta, Shannon G. -- University of Tennessee Health Sciences Center
Gestational Drugs and Nicotine Self-Administration

McCaffrey, Daniel F. -- Rand Corporation
Causal Effects of Community-Based Treatments for Youths

McGehee, Daniel S. -- University of Chicago
Nicotinic Modulation of the Mesoaccumbens DA System

McLaughlin, Jay P. -- University of Washington
Endogenous Opioid Mediation of Stress and Drug Reward

Melloni, Richard H. -- Northeastern University
Adolescent Anabolic Steroids, Vasopressin and Aggression

Menard, Scott W. -- University of Colorado at Boulder
Inhalant Abuse Across Generations In A National Sample

Mendelson, Jack H. -- McLean Hospital, Belmont, MA
Neurobiology of Nicotine: Hormones and Behavior

Miller, Bonnie C. -- University of Texas SW Medical Center, Dallas
Opioid Receptors On T Cell Subsets

Moeller, Frederick G. -- University of Texas Health Sciences Center, Houston
Serotonin, Drug Use and MDMA Induced Deficits

Morgan, Michael M. -- Washington State University
Cellular Mechanisms of Opioid Tolerance

Morrell, Joan I. - Rutgers, The State University of New Jersey, Newark
Maternal Rat Preferences for Pups Versus Cocaine

Nagarkatti, Prakash S. -- Virginia Commonwealth University
Cannabinoid-Induced Apoptosis In T Cell Regulation

Neaigus, Alan -- National Development & Research Institutes
Hiv Risk and Neighborhood Networks of New IDUs

Nichols, David E. -- Purdue University West Lafayette
Stereochemical Aspects of Hallucinogenesis

Olsen, George D. -- Oregon Health & Science University
Mu Opioid Receptor Regulation In Neonatal Brainstem

Pappas, George D. -- University of Illinois at Chicago
Analgesic Effects of Adrenal Chromaffin Cell Transplants

Peterson, Phillip K. -- Minneapolis Medical Research Foundation, Inc.
Modulation of Cell-Mediated Immune Function by Opiates

Piasecki, Thomas M. -- University of Missouri, Columbia
Ecology Momentary Assessment of College Smoking

Picciotto, Marina R. -- Yale University
Galanin-Opiate Interactions

Pickel, Virginia M. -- Weill Medical College of Cornell University
Em-Transmitter Interactions of Striatal Opioid Neurons

Pierce, R.C. -- Boston University Medical Campus
mPFC, N. Accumbens and Reinstatement of Cocaine Seeking

Ramaswami, Mani -- University of Arizona
Fos, Jun and Control of Synaptic Plasticity

Reggio, Patricia H. -- Kennesaw State University
Molecular Determinants for Cannabinoid Activity

Schafer, William R. -- University of California, San Diego
Analysis of Touch Response and Habituation In C. Elegans

Strathdee, Steffanie A. -- Johns Hopkins University
Incidence of HIV Infection In A Cohort of IV Drug Users

Takahashi, Traci A. -- University of Washington
Hospital Care IDUs With Soft Tissue Infections

Tapert, Susan F. -- Veterans Medical Research Foundation, San Diego
fMRI and Cognition In Adolescent MDMA and Cannabis Users

Tashkin, Donald P. -- University of California, Los Angeles
Cocaine Smoking Effects On Lung Immunity and Host Defense

Terman, Gregory W. -- University of Washington
Modulation of Spinal Cord LTP by Kappa Opioids

Toll, Lawrence -- SRI International
Computational Approach To Neuropeptides and Drug Abuse

Van Bockstaele, Elisabeth J. -- Thomas Jefferson University
Very Low Naltrexone Treatment of Opiate Withdrawal

Vaughan, Roxanne A. -- University of North Dakota
Affinity Labeling the Dopamine Transporter Active Site

Vaughan, Roxanne A. -- University of North Dakota
Phosphorylation and Regulation of Dopamine Transporters

Wagner, John J. - North Dakota State University
Cocaine-Induced Metaplasticity In the Hippocampus

Wakschlag, Lauren S. -- University of Chicago
Prenatal Smoking and Patterns of Youth Problem Behavior

Wang, Qiang -- University of Missouri, Kansas City
Metabotropic Glutamate Regulation of Amphetamine Action

Weisner, Constance M. -- University of California, San Francisco
Course of Problems In Adolescent Drug Treatment Intakes

Winger, Gail -- University of Michigan at Ann Arbor
Behavioral Economic Analysis of Polydrug Abuse

Witte, Susan S. -- Columbia University New York Morningside
Defining Fatherhood Among Drug Dependent Men

Wolf, Marina E. -- Finch University of Health Sciences, Chicago Medical School
Dopamine and Glutamate Receptor Interactions

Wu, Li-Tzy -- Research Triangle Institute
Inhalant Use/Dependence: Incidence and Comorbidity

Xie, Xiang-Qun -- University of Connecticut, Storrs
Advanced Isotope Aided NMR For Cb2 Structural Study

Yeomans, David C. -- Stanford University
In Vivo Genetic Manipulation of Neuronal Excitability

Zarkin, Gary A. -- Research Triangle Institute
Three Methods for Costing Methadone Treatment Services

Zhan, Chang-Guo -- Columbia University Health Sciences
Redesign of Butyrylcholinesterase for Cocaine Metabolism

Zhdanova, Irina V. -- Boston University Medical Campus
Cocaine-Induced Behaviors In Larval Zebrafish

Zhu, Hong -- University of Mississippi Medical Center
Neuronal Mechanisms of Opioid Action


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