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National Institute on Drug Abuse

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

May, 2000

Program Activities

New PAs/RFAs


On January 19, 2000, NIDA issued a Program Announcement entitled Neurobiological and Behavioral Research on Nicotine and Tobacco Components (PA-00-45). The purpose of this PA is to expand the basic science knowledge base on the neurobiological and behavioral effects of nicotine and associated tobacco chemicals, as part of continuing efforts to explain and prevent their use and to develop effective treatments for nicotine addiction. This PA encourages research on any aspect of the effects of nicotine and other tobacco components, using neurobiological, behavioral, or other methods in humans, animals, or in vitro systems, that seeks to explain nicotine use, addiction, or other effects in humans.

On February 10, 2000, NIDA issued a Supplement Announcement entitled Supplements for the Study of Drug Abuse and HIV/AIDS (PAS-00-058). With this Supplement Announcement, NIDA plans to continue to develop a strong multidisciplinary research program in response to the complex challenges of drug abuse and HIV/AIDS. The Supplement Program is designed to encourage and enhance interactive, multidisciplinary collaborative projects involving researchers with primary foci both within and outside the area of drug abuse.

On February 10, 2000, NIDA issued a Program Announcement entitled NIDA Small Grants Program (PAR-00-059). This PA updates and replaces PAR-97-038, published in the NIH Guide for Contracts and Grants Vol. 26, No. 6, February 21, 1997. The small grants program accepts applications that fall within any of the scientific program interests of NIDA. This includes a wide variety of biomedical, behavioral, clinical, health services, epidemiological, behavioral and prevention research areas relevant to the study of drug abuse or addiction processes.

PAs With Other NIH Components

On January 19, 2000, NIDA, in conjunction with a number of other NIH Institutes, issued a Program Announcement entitled Biobehavioral Research for Effective Sleep (PA-00-046). The goal of this PA is to stimulate clinical and applied research on behavioral, psychosocial, and physiological consequences of acute and chronic partial sleep deprivation in either chronically ill or healthy individuals and to develop environmental, clinical management, and other interventions with the potential to reduce sleep disturbances and significantly improve the health of large numbers of people.

On February 22, 2000, NIDA, in conjunction with a number of other NIH Institutes, issued a Program Announcement entitled Mechanisms in HIV Dementia and Other CNS Diseases (PAS-00-065). This PA invites investigator-initiated grant proposals to study potential common immunological and inflammatory mechanisms involved in the etiology of HIV-1 associated dementia (HAD) and neurodegenerative and/or autoimmune diseases of the nervous system such as Alzheimer's, Parkinson's disease and multiple sclerosis. One intent of this PA is to encourage basic and clinical scientists who have been working in the previously disparate areas of infectious, autoimmune and neurodegenerative disease to develop multidisciplinary collaborations to search for common factors in the causation of these and other related diseases.

On March 13, 2000, NIDA, in conjunction with the National Institute of Mental Health (NIMH) issued a Program Announcement entitled Interventions for Suicidal Youth (PA-00-077). The purpose of this PA is to support efforts to develop and test interventions that build on risk and protective factors for suicidal behaviors in youth. This PA identifies the need to test the effectiveness of interventions for reducing suicidal behavior from a number of approaches, ranging from broad-based community or school-based prevention efforts, to more targeted approaches that reduce suicidal behavior in youth with identified mental or substance abuse disorders.

On April 6, 2000, NIDA, in conjunction with numerous other NIH Institutes, issued a Program Announcement entitled Earth-Based Research Relevant to the Space Environment (PA-00-088). The purpose of this PA is to stimulate ground-based research on basic, applied and clinical biomedical and behavioral problems that are relevant to human space flight or that could use the space environment as a laboratory. Although none of the research supported under this initiative would be conducted is space, it is anticipated that it would form a basis for future competitively reviewed studies which could be conducted on the International Space Station, or other space flight opportunities, by skilled on-board specialists.

RFAs With Other NIH Components

On February 14, 2000, NIDA, in conjunction with several other NIH Institutes, issued an RFA entitled Adolescent Medicine Trials Network for HIV/AIDS Interventions (HD-00-002). The purpose of this RFA is to support a research network infrastructure with the capacity for behavioral, microbicidal, prophylactic, therapeutic, and vaccine trials to take full advantage of the results of the detailed observational and laboratory-intensive studies of the Adolescent Medicine HIV/AIDS Research Network.

On February 16, 2000, NIDA, in conjunction with numerous other NIH Institutes, issued an RFA entitled Mutagenesis Screens/Phenotyping Tools for Zebrafish (HD-00-004). The purpose of this RFA is to encourage research designed to exploit the power of mutagenesis screening in zebrafish in order to detect and characterize genes, pathways and phenotypes of interest in development, behavior, organ formation, and disease processes. Applications that propose to advance the technologies associated with such phenotyping are also welcome.

Other Program Activities

National Drug Abuse Treatment Clinical Trials Network

Nineteen applications were received for NIDA's re-issuance of the "National Drug Abuse Treatment Clinical Trials Network" RFA on March 16, 2000. This RFA is the second issue with the intention to develop a geographically diverse and encompassing network. Five to six new awards will be made in September 2000 and will double the size of the Clinical Trials Network. In February 2000, a sixth node, New York, was awarded. The PI is Dr. John Rotrosen who is affiliated with New York University.

MATTT Meeting

The Methamphetamine Addiction Treatment Think Tank (MATTT) meeting was held on January 12, 2000 to review the existing science and to brainstorm on treatment strategies. This is the first step following the NIDA Director's initiative to establish a methamphetamine dependence pharmacotherapy program.

Clinical Research Efficacy Screening Trial (CREST-I) Study Completion

Each NIDA/VA Medications Development Research Unit has completed recruiting 60 subjects each in their CREST studies (three medications each and an unmatched placebo). The data are being analyzed and were presented for consultant's review on April 26, 2000.

GBR 12909

The study report from the Phase I (healthy volunteer) study is complete and will be reviewed in May 2000 in planning for the next cocaine interaction study. The study showed 30-40% dopamine transporter occupancy at the 100mg dose level. Based on primate data this may be clinically meaningful in cocaine treatment.

Methylphenidate in Cocaine Dependant Individuals with ADD

This open label feasibility study showed promising effect of methylphenidate in decreasing cocaine use in this co-morbid subgroup. NIDA has awarded a grant for Dr. Frances Levin to further study methylphenidate in this subgroup in a large double blind study.

New Clinical Trials Operations (CTO) Contract Protocol Reviews

Tolcapone, Ondansteron, Modafinil, and Metyrapone were all peer reviewed for studies through the CTO mechanism. All drugs were approved for studies at different phases, and protocols are being submitted to IRBs for review.

Update on Selegiline

In the immediate release study the last few subjects are finishing the study. The protocol for the Selegiline Transdermal System study is in review at the level of the VA Cooperative Studies Program review committee.

Strategic Planning for Medications Development

On April 5, 2000 the Medications Development Program of the Division of Treatment Research and Development presented a comprehensive description of its current mission and focus, capabilities, portfolio development, asset deployment, and future directions and plans to members of the National Advisory Council on Drug Abuse and other invited consultants. Presentations by all branches and programs involved in medications discovery and development occurred throughout the day, with active question and answer sessions. An executive session of the reviewers occurred on April 6, 2000 with the goal of presenting recommendations to NIDA Director, Dr. Alan Leshner.

Desipramine in Cocaine Dependence

Several past studies have suggested that desipramine might potentially be effective in the treatment of cocaine dependence, but the results were equivocal and inconsistent. Therefore, NIDA supported additional studies with desipramine under better- controlled trial conditions and in selected populations of cocaine addicts. These studies have been recently completed. On March 10, 2000, DTR&D/NIDA held a symposium to evaluate the results of these trials. The opinions of independent NIDA consultants were solicited as to whether the data warranted initiation of phase III trials with desipramine as potential therapy for cocaine dependence.

Dr. Thomas Kosten presented results of a trial with desipramine in treating methadone or buprenorphine maintained cocaine addicts. Dr. Edward Nunes presented a trial that tested the efficacy of desipramine in treating depressed cocaine addicts. Dr. Jane Campbell compared the efficacy of desipramine in cocaine- addicted men versus cocaine- addicted women. Dr. Ivan Montoya presented the results of a trial conducted at the Addiction Recent Center. Drs. Frank Gawin and Elena Stark presented the results of their study comparing the effects of desipramine with flupenthixol (a neuroleptic) and a study evaluating the concept of a specific therapeutic window that may be critically determinative for demonstrating efficacy of desipramine. Globally, the results of these studies showed either no effect or marginal effect only in selected populations of patients. However, Dr. Gawin's data suggested that there might be a therapeutic window for desipramine effects (plasma concentrations of 30 - 80 ng/ml), and that concentrations below or above this window are ineffective. Such window could have a theoretical merit. Because desipramine is a pro-dopaminergic and pro-noradrenergic drug, optimal concentrations in blood could potentially compensate for an apparent dopaminergic and noradrenergic deficiency in addicts, while doses above this optimum could mimic cocaine euphorigenic effects and induce craving.

The collective opinion of consultants was that these data do not warrant NIDA's engagement in a phase III trial with desipramine, but that NIDA should further evaluate the concept of a desipramine therapeutic window in a phase II studies, using independent contract investigators. The Clinical Trials Branch, DTR&D is preparing to undertake such a trial with desipramine.

Review of Progress, Potential Anti-Cocaine Vaccine

On March 24, DTR&D/NIDA attended a meeting with Drs. Thomas Kosten, Dr. Marian Fishman and representatives of the British company Cantab (which holds the rights to this particular vaccine), discussing future clinical studies with anti-cocaine antibodies. Dr. Kosten is the Principal Investigator of a Strategic Program for Innovative Research on Cocaine (and other Psychomotor Stimulants) Addiction Pharmacotherapy (SPIRCAP) grant which was awarded to further research and development of an anti-cocaine vaccine. Dr. Kosten has already completed a Phase I safety study of the vaccine, and he and Dr. Fischman are planning additional studies.

Summer Internship Program/Summer Research Fellowship Program

The NIH Summer Internship Program (for students in high school through graduate school) and the Summer Research Fellowship Program (for medical and dental students) accepted electronic applications from Nov. 15, 1999 to March 1, 2000. NIDA IRP received over 200 applications from students interested in a summer internship experience in one of the intramural labs. Students are currently being selected. It is anticipated that about 15 students will be accepted into the program. Dr. Stephen Heishman coordinates the program and can be contacted at

Minority Recruitment & Training Program

The Minority Recruitment & Training Program has been accepting applications for its Summer 2000 Program. The NIDA, IRP Minority Recruitment & Training Program (MRTP) is an intramural program that provides training opportunities for students from under-represented groups who are interested in the scientific basis of drug abuse. In this program, students gain basic science and/or clinical laboratory experience, attend student seminars and participate in a summer poster presentation. The goal of this program is to expose students to the realities of research, from experimental design to data analysis, interpretation and presentation. To request an application or to receive additional information, contact: Christie Brannock at

NIDA's New and Competing Awards Since January 2000

Abrams, David B. --- Miriam Hospital
Nicotine Dependence: Risk & Recovery Over Generations

Adler, Martin W. --- Temple University School of Medicine
College on Problems of Drug Dependence Annual Meeting

Balster, Robert --- Virginia Commonwealth University
The Behavioral Pharmacology of Phencyclidine

Bardo, Michael T. --- University of Kentucky
Novelty, Dopamine and Response to Amphetamine

Bickel, Warren K. --- University of Vermont
Improving Combined Buprenorphine- Behavioral Treatment

Booth, Robert E. --- University of Colorado
Intervention to Reduce Injection Drug Use

Budney, Alan J. --- University of Vermont State Agricultural College
Clinical Significance of Marijuana Withdrawal

Butelman, Eduardo R. --- Rockefeller University
Effects of Systemically Administered Dynorphins

Butler, Stephen F. --- Innovative Training Systems
A Spanish Adaption of the ASI -- Multimedia Version

Caggiula, Anthony R. --- University of Pittsburgh
Effects of Self-Administered vs Noncontingent Nicotine

Caron, Marc G. --- Duke University Medical Center
Genetic Analysis of Dopaminergic Reward Mechanism

Caudle, Robert M. --- University of Florida
Nociception and NMDA Receptor Phosphorylation

Chen, Hao --- Oceanix Biosciences Corporation
Profiling Data Base for Cocaine Medication

Corrigall, William A. --- ARF Division
Cholinergic and Opiate Mechanisms in Drug Reinforcement

Coscia, Carmine J. --- St Louis University School of Medicine
Opioid Modulation of Astrocyte Proliferation

Coussons-Read, Mary E. --- University Of Colorado
Effects of Morphine on Pulmonary Influenza Infection

Crowley, Thomas J. --- University of Colorado Health Science Center
Substance-Use and Conduct Disorder: Motility, Neuropsychology

Cunningham, Susanna L. --- University of Washington
Addiction: Hijacking the Brain

Dansereau, Donald F. --- Texas Christian University
Cognitive Enhancements for Treatment of Probationers

Deadwyler, Samuel A. --- Wake Forest University School Of Medicine
Long-Term Brain-Behavior Effects of Delta-9-THC

Deren, Sherry --- National Development and Research Institute
Drug Users in New York and Puerto Rico: HIV Risk Behavior

Devi, Lakshmi A. --- New York University School of Medicine
Post-Translational Regulation of Opioid Receptors

Donovan, Stephen J. --- Research Foundation of Mental/Hygiene Inc.
Temper, Mood Swings and Marijuana-A Treatable Syndrome

Drucker, Ernest --- Montefiore Medical Center
Office-Based Methadone Prescribing II

Dubner, Ronald --- University of Maryland, Baltimore
CNS Modulation of Persistent Pain and Spinal Plasticity

Edlin, Brian R. --- University of California, San Francisco
Syringe Exchange Peer Mobilization Intervention

Edlin, Brian R. --- University of California -Department of Family-Community Medicine
Hepatitis C Virus Transmission in Crack Cocaine Smokers

Evans, Suzette M. --- Research Foundation for Mental Hygiene
Vulnerability to Anxiolytic Abuse in Women

Fendrich, Michael --- University of Illinois, Chicago
Feasibility of Biological Measurement in Drug Surveys

Galizio, J. Mark --- University of North Carolina Wilmington
Drugs of Abuse and Complex Behavior

Garvey, Arthur J. --- Harvard School of Dental Medicine
Individualizing Treatment for Addicted Smokers

Gold, Michael S. --- University of Maryland at Baltimore
Inflammation-Induced Plasticity Trigeminal Sensory Neurons

Gudelsky, Gary A. --- University Of Cincinnati
Determinants and Consequences of MDMA Neurotoxicity

Guo, Jie --- University of Washington
Developmental Relations of Substance Use and Risky Sex

Harlan, Richard E. --- Tulane School of Medical
Thalamo-Striatal Mechanisms of Morphine Action

Houghten, Richard A. --- Torrey Pines Institute for Molecular Studies
Identification of Receptor Specific Opioid Ligands

Howell, Leonard L. --- Emory University
Cocaine Use and Monoamine Function in Nonhuman Primates

Johannes, Catherine B. --- New England Research Institute, Inc.
Pharmacology for Chronic Pain: An Interactive CD Rom

Kalivas, Peter W. --- Medical University of South Carolina
Glutamate and Craving for Cocaine

Kandel, Denise B. --- Columbia University
Nicotine Dependence Among U.S. Youths

Kosten, Thomas R. --- Yale University
Comorbidity in Cocaine and Opioid Pharmacotherapy

Kramer, Hal K. --- New York University Medical Center
Mechanisms Involved in Opioid Receptor Down-Regulation

Leonard, Sherry S. --- University of Colorado Health Science Center
Human Brain Nicotinic Receptors and Nicotine Addiction

Liu-Chen, Lee-Yuan --- Temple University School of Medicine
Molecular Characterization of Opioid Receptors

Loeber, Rolf --- Western Psychological Institute/Clinic UPMC
Development of Substance Use in Girls

Lysle, Donald T. --- University of North Carolina at Chapel Hill
Determinants of Opioid/Immune Interactions

Macdonald, J. Christie --- University of Sydney
Opioid Withdrawal Mechanisms in Midbrain Neurons

Magura, Stephen --- National Development and Research Institute Inc.
Service Outreach to Homeless Drug Users

Marcus, Marsha D. --- Western Psychology Institute and Clinic
Bupropion and Weight Control for Smoking Cessation

Mayes, Linda C. --- Yale University School Of Medicine
Arousal Regulatory Functions in Cocaine-Exposed Children

McLellan, A. Thomas --- University Of Pennsylvania
Drug Abuse Treatment Evaluation Center

Metherate, Raju S. --- University of California Irvine
Functions of Nicotine Receptors in Sensory Neocortex

Miller, Maureen --- National Development & Research
Networks, Resources and Risk Among Women Drug Users

Miller, Richard J. --- University of Chicago
Chemokine Receptor Function in the Nervous System

Moeller, Frederick G. --- University of Texas at Houston
Serotonin, Impulsivity and Cocaine Dependence Treatment

Morrissey, Joseph P. --- University of North Carolina at Chapel Hill
Impacts of Managed Care on Substance Abuse Service Linkages

Nader, Michael A. --- Wake Forest University School of Medicine
Social Stress: Vulnerability to Cocaine Abuse

Pacula, Rosalie L. --- Rand
Are There Economic Costs of Marijuana Use?

Pasternak, Gavril W. --- Sloan-Kettering Institute/Cancer Research
Pharmacology of Opioid Receptor Subtypes

Pentel, Paul R. --- Hennepin County Medical Center
Immunization to Block the Effects of Nicotine

Pentz, Mary A. --- University of Southern California
The Multi-State Prevention Teleconference Trial

Peoples, Laura L. --- University Of Pennsylvania
Cue-Controlled Drug Taking: Accumbal Neurophysiology

Perkins, Kenneth A. --- Western Psychology Institute and Clinic
Individual Variation in Nicotine Sensitivity in Humans

Pope, Harrison G, Jr. --- McLean Hospital
Cognitive Consequences of Long-Term Marijuana Use

Porco, Travis C. --- San Francisco Department/Public Health
Forecasting HIV Evolution in IDUs and Other Populations

Richter, Kimber --- University of Kansas Medical Center
Addressing Nicotine Addiction in Drug Abuse Patients

Roberts, Laura W. --- University New Mexico, Health Science Center
Stigma and Rurality: Drug Abuse, HIV/STD and Mental Illness

Roerig, Sandra C. --- LSU Medical Center
Spinal Nitric Oxide in Chronic Inflammatory Pain

Rotrosen, John P. --- NYU/NY VA Medical Center
NIDA Clinical Trials Network - NYR East Side Node

Sanders-Bush, Elaine --- Vanderbilt University Medical Center
Hallucinogens and Serotonin Signal Transduction

Schottenfeld, Richard S. --- Connecticut Mental Health Center
Improving Efficacy of Drug Abuse Treatment

Schottenfeld, Richard S. --- Connecticut Mental Health Center
Disulfiram for Cocaine Abuse in Buprenorphine Treatment

Sherman, Steven J. --- Indiana University
The Social Psychology of Group Perception and Smoking

Shi, Wei-Xing --- Yale University
DA-NE Interaction in Drug Abuse

Simone, Donald A. --- University of Minnesota
Cannabinoid Modulation of Hyperalgesia

Smith, James E. --- Wake Forest University School of Medicine
Neurobiology of Speedball Self-Administration

Smith, Sheryl S. --- Research Foundation of SUNY
Steroids and GABA: Physiology of Receptor Subunit Changes

Sopori, Mohan L. --- Lovelace Biomedical and Environmental Research Institute
Mechanism of Cigarette Smoke-Induced Immunosuppression

Stark, Michael J. --- Oregon Health Division
Reducing HIV and Domestic Violence Risk in Women Offenders

Stein, Elliot A. --- Medical College of Wisconsin
Functional MFRI of Human Drug Abuse

Stitzer, Maxine L. --- Society for Research on Nicotine
Society for Research on Nicotine and Tobacco Annual Meeting

Strauss, Shiela M. --- National Development and Research Institute Inc.
Drug Users' Self-Reported HIV Status: Validity/Methods

Tarter, Ralph E. --- Western Psychological Institute and Clinic
Drug Abuse Vulnerability: Mechanisms and Manifestations

Tietz, Elizabeth I. --- Medical College of Ohio
Hippocampal Benzodiazepine Tolerance

Tiffany, Stephen T. --- Purdue University
Laboratory Investigations of Craving for Cigarettes

Trzcinska, Monika M. --- Zebra Pharmaceuticals, Inc.
Behavioral Evaluation of Novel DAT Antagonist

Tsuang, Ming T. --- Massachusetts Mental Health Research Corporation
Molecular Genetics of Heroin Dependence

Vanyukov, Michael M. --- Western Psychological Institute and Clinic
Substance Abuse and the Dopamine System Genes

Vathy, Ilona --- Albert Einstein College of Medicine
Opiates and CNS Development

Vlahov, David --- New York Academy of Medicine
Hepatitis C in New IDUs: Implications for HIV Prevention

Vogel, Zvi --- Weizmann Institute of Science
Mechanism of Adenylyl Cyclase Superactivation by Opiates

Vorhees, Charles V. --- Children's Hospital Research Foundation
Developmental Effects of Methlenedioxymethamphetamine

Walker, J. Michael --- Brown University
Pain Modulation by Endogenous Cannabinoids

Weinstein, Harel --- Mount Sinai School of Medicine
Hallucinogens and 5-Ht2a Receptors: Mechanisms and Effects

White, Francis J. --- FUHS/Chicago Medical School
Cocaine Addiction and Neuronal Excitability

Wilens, Timothy E. --- Massachusetts General Hospital
Substance Abuse in Juvenile Bipolar Disorder

Wines, James D. Jr. --- Alcohol and Drug Abuse Research Center
Drug-Related Suicidal and/or Homicidal Behavior

Winsauer, Peter J. --- LSU Medical Center
Cocaine Self-Adminstration: Effects on Learning

Winters, Ken C. --- University of Minnesota
Youth Drug Abuse, ADHD, and Related Disruptive Behaviors

Wolf, Marina E. --- FUHS/Chicago Medical School
Glutamate and Psychostimulant-Induced Neuroadaptations

Woods, James H. --- University of Michigan
Narcotic Drug and Opioid Peptide Basic Research Project

Woolverton, William L. --- University of Mississippi Medical Center
Determinants of Drug Choice in Monkeys

Worley, Paul F. --- Johns Hopkins University School of Medicine
Analysis of a Novel Cocaine-Induced IEG

Zacny, James P. --- University of Chicago
Characterizing Psychoactive Effects of Inhalants

Zemlan, Frank P. --- Mind Probes Inc.
Neurotoxin Discovery Platform - Drugs of Abuse

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