Full Text DA-94-003 HUMAN BASIC AND CLINICAL NEUROSCIENCE OF DRUG ADDICTION NIH GUIDE, Volume 23, Number 3, January 21, 1994 RFA: DA-94-003 P.T. 34 Keywords: Addiction Neuroscience Neurophysiology Etiology Brain National Institute on Drug Abuse Letter of Intent Receipt Date: March 12, 1994 Application Receipt Date: April 12, 1994 PURPOSE A generation of neuroscientific research utilizing animal models has provided the identification of receptors for every major abused drug and many of their endogenous ligands. A variety of models has been developed to explain the fundamental behavioral and biological mechanisms of addiction, e.g., brain reward, tolerance, and dependence. These discoveries and models, coupled with the rapid advances in noninvasive brain imaging methodology, now make it feasible to study drug addiction and the human brain to determine the etiology and the biomedical and biobehavioral consequences of drug abuse, as well as the effects of treatment of this disorder. The National Institute on Drug Abuse (NIDA) proposes to initiate a major program using noninvasive technologies or autopsy materials to study the human brain and the etiology and consequences of drug abuse and to translate this information into novel prevention, diagnostic, and treatment strategies. Research grant applications to use current, or to develop new, noninvasive techniques to assess neuroanatomical, neurochemical, or other functional differences or changes in human brain that contribute to vulnerability to drug abuse, are a consequence of drug use, or result from pharmacological or non-pharmacological treatment are therefore invited. These applications may establish integrated, multidisciplinary imaging programs in which basic and clinical studies are conducted in humans, or the applications may request support for smaller studies. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), Human Basic and Clinical Neuroscience of Drug Addiction, is related to the priority areas of tobacco, alcohol and other drugs, and maternal and infant health. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0, or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by foreign and domestic, for-profit and non-profit, public and private organizations, e.g., colleges, universities, hospitals, laboratories, units of State and local government, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. Foreign institutions are not eligible for the program project (P01) or center grant (P50) awards. MECHANISMS OF SUPPORT Support mechanisms include research project grants (R01), program projects (P01), center grants (P50), and small grants (R03). Investigators may also respond to this RFA under the Interactive Research Project Grant Program (IRPG), which utilizes the R01 mechanism. If an investigator wishes to respond under an IRPG, additional requirements must be met as described in PA-93-078. However, if the IRPG mechanism is used under this RFA, this RFA deadline receipt date takes precedent over the IRPG special receipt date. Most investigator-initiated research is supported by research project grants (R01). Research grants are awarded to institutions on behalf of Principal Investigators who have designed and will direct a specific project or set of projects. Research project grants can be renewed at intervals or supplemented through the formal submission and review process described below. Investigator(s) may apply for a renewal (competing continuation) of R01 grants by submitting an application for further support, including a report of progress and including specific plans for future work. Applications for competing supplements to expand the scope of already-awarded grants that utilize the R01, P01, or P50 mechanism to include human neuroscience may be submitted. FUNDS AVAILABLE It is anticipated that approximately $10 million will be available to support the first year of the human neuroscience research program. Because the nature and scope of the research proposed in response to this RFA may vary, the size of an award will vary also. However, it is anticipated that approximately 20 new awards will be made under this announcement. RESEARCH OBJECTIVES This research program is intended to support (1) individual research project grants on basic and clinical human neuroscience and (2) the establishment of human neuroscience research centers (HNRCs) to conduct interdisciplinary research on the human neuroscience of drug addiction. Research using animals is not excluded, but their use in projects submitted under this RFA must be specifically justified. Effort is to be made to use state-of-the-science approaches. Human neuroscience research within an HNRC should involve the systematic development and integration of knowledge derived from a variety of sources, and should utilize a number of designs. The proposed research must be organized around a central theme. The theme of the HNRC should clearly relate to investigating the human neuroscience of drug addiction. Both individual research project grants and HNRCs funded under this RFA may conduct research that uses various imaging or other innovative technologies, living neural tissue, or postmortem tissue to: (1) elucidate in humans the basic mechanisms of action of drugs of abuse, including interaction with other drugs and mental conditions; (2) examine the neurobiological factors that contribute to vulnerability to drug abuse; (3) examine the CNS status of patients during diagnosis and treatment for drug dependency disorders. 1. Basic Human Neuroscience Investigators are invited to study the effects of substance abuse on the structure and function of the human brain using various imaging and other technologies (e.g., ligand PET scanning, functional magnetic resonance imaging, magnetic source imaging, electroencephalography, magnetic resonance spectroscopy), autopsy material, or other methods (e.g., neural tissue transplantation, neuron cultures, analytical neurochemistry). The main goals of the basic research supported through this initiative are to: (1) identify in humans the neuronal systems involved in mediating the pleasurable or reinforcing experiences associated with substance abuse (the human brain reward system), and (2) characterize in humans the neurochemical, neuroanatomical, and neurophysiological changes that underlie states of drug tolerance and dependence, as well as characterize the reversible and irreversible brain changes that result from drug abuse. Investigators are further encouraged to verify in man observations made in animal studies that drug abuse produces long-lasting changes in neurochemical markers and morphological features of specific sets of neurons. The effects of different types of drugs of abuse on neurochemical markers could be assayed in postmortem human brain tissue samples. Such studies should measure fundamental neuronal and glial structure and function including morphology, activity of enzymes involved in neurotransmitter synthesis and degradation, receptor densities and distribution, second messenger systems, and measurements of gene expression. Of particular interest are studies that will take advantage of the opportunity to correlate directly the changes in the patterns of biologic activity in the human brain with the subjective experiences of the individual exposed to drugs of abuse. This research should help elucidate the precise neural mechanisms affected by drugs of abuse as well as reveal how drug-induced alterations might lead to and maintain drug-seeking behavior and addiction. Also important are studies assessing brain function during various stages of withdrawal and abstinence, which should provide important information about the neural substrates involved in drug craving. Studies are also encouraged that would refine current imaging techniques or develop new ones, elucidating the basic mechanisms and correlations that relate images to neuronal activity, for example, establishing the mathematical relationships between blood flow, metabolism, and cellular activity, or providing greater levels of refinement for viewing anatomical structures; e.g., applications of magnetic resonance microscopy that attempt to provide resolution at the cellular level. Research in the chemistry necessary to human brain imaging is also encouraged, for example, the synthesis of novel imaging reagents for use in humans. Another area of interest is the application of imaging technologies to pharmacokinetics. 2. Vulnerability and Etiological Investigations In humans, neurobiological factors that relate to high vulnerability to abuse drugs or to high vulnerability to suffer the adverse health consequences of drug abuse are not currently defined. NIDA is also interested in research on neurobiological aspects of drug abuse that might be unique to special groups, such as women, youths, and minority populations. Applications for support under this RFA will use original approaches to apply the latest in imaging and other innovative techniques to the examination of neurobiological factors underlying the etiology of and vulnerability to drug abuse in humans. Such projects might use noninvasive techniques to: (l) examine factors contributing to the biomedical etiology of drug abuse; for example, studies evaluating genetic, developmental, and environmental factors in drug addiction, including nutritional and environmental toxic elements or examining the neurobiological relationship between early use of tobacco and alcohol and later development of cocaine and heroin addictions; (2) identify the type and distribution of the biomedical consequences of abusing drugs because of as-yet-unidentified neurobiological predispositions; (3) assess the prevalence, distribution, and epidemiology of biobehavioral risk factors underlying the vulnerability to abuse drugs. This might include investigations of the role of stress in vulnerability to drug addiction (e.g., links between post traumatic stress disorders and drug seeking behaviors); and (4) modify and further develop existing technologies and methodologies for studying the neurobiological risk factors of drug abuse. Projects should develop new information about how individual differences in genetics, neurobiological profiles, or psychological behaviors predict drug abuse or, alternatively, protect from drug abuse. 3. Clinical and Treatment Neuroscience Clinical and treatment-oriented neurobiological researchers are encouraged to submit proposals that utilize state-of-the-art brain imaging, analytical neurochemistry, electrophysiology, neuropsychological assessment, genetic analysis, and other technology to elucidate the CNS status of patients during various stages of diagnosis and treatment of drug dependency disorders. For example, studies might examine neurotransmitter metabolites appearing in blood and cerebrospinal fluid as neurochemical markers for diagnosis, as correlates of mood and behavior, and as predictors of clinical outcome. This example also encompasses metabolic changes in response to various treatment interventions, pharmacological, behavioral, and psychosocial. It is important to describe the changes that occur in the endogenous opioid system, neuroendocrine system, and other neuronal systems in patients throughout all stages of the addictive process, including protracted abstinence, response to treatment, recovery, and long-term cognitive, perceptual, motor, or other deficits resulting from drug abuse. Studies evaluating the relationship between drug seeking behavior and preexisting neurological deficits, particularly hypofrontality and attention deficit hyperactivity disorders, or the comorbidity of drug use and of other mental disorders, especially depression, schizophrenia, and anti-social personality, are also encouraged. Research investigating the relationship between drug abuse and development of various neurological disorders such as Parkinson disease, Alzheimer's disease, etc., is also of interest. Since many drug addicts are polydrug abusers, studies to investigate the neurological, neurochemical, pharmacological, pathological, and psychological consequences of interactions among abused drugs, such as cocaine, heroin, alcohol, nicotine, marijuana, anabolic steroids, inhalants, etc., are also encouraged. SPECIAL REQUIREMENTS There are special requirements for the center grant (P50), program project (P01), and small grant (R03) applications. If an applicant intends to apply under this RFA utilizing either of those support mechanisms, they may contact the program person listed under INQUIRIES for further information. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and both genders in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder, or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale for exclusion or inadequate representation should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objective of the study. This information should be included in the form PHS 398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of the United States racial/ethnic minority populations (i.e., American Indian or Alaskan Natives, Asians or Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by March 12, 1994, a letter of intent that includes a descriptive title of the proposed research, the proposed mechanism of support, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of this RFA. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that is contains allows NIDA staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to: Director, Office of Extramural Program Review National Institute on Drug Abuse 5600 Fishers Lane, Room 10-42 Rockville, MD 20857 Telephone: (301) 443-2755 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 240, Bethesda, MD 20892, telephone 301-710-0267. The RFA label in the application form PHS 398 must be affixed to the bottom of the original face page. Failure to use the RFA label and to follow instructions could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed in Item 2a on the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application and three signed photocopies in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies of the application must also be sent to: Director, Office of Extramural Program Review National Institute on Drug Abuse 5600 Fishers Lane, Room 10-42 Rockville, MD 20857 Applications must be received by April 12, 1994, and will be reviewed according to the following review schedule: Application Receipt Date: April 12, 1994 Initial Review: July 1994 Advisory Council Review: September 1994 Earliest Award Date: September 1994 R01, P01, R03, or IRPG applications received after the receipt date will be held for the next regular receipt date and reviewed under standard circumstances. However, they will not be considered as a response to this RFA. P50 applications received after the above receipt date will be returned to the applicant without review. REVIEW CONSIDERATIONS The Division of Research Grants, NIH, serves as a central point for receipt of applications for most discretionary DHHS grant programs. Applications received under this RFA will be assigned to a special review group convened by NIDA. The review group, consisting of experts in basic and clinical human neuroscience research, as warranted by the applications, will review the applications for scientific and technical merit in accordance with the standard NIH peer review procedures. Pre-review site visits will not be made, and applications will not be deferred for site visit; therefore, applications must be complete when submitted. Notification of the review recommendations will be sent to the applicant after the initial review. Those applications that are complete and responsive will be evaluated in accordance with the appropriate criteria for scientific/technical merit by a peer review group convened by NIDA. Applications may be triaged by an NIDA-convened peer review group according to scientific merit relative to other applications received in response to this RFA. Those applications judged to be competitive will be evaluated further for scientific/technical merit by the usual peer review procedures. Following this review, the applications will be given a secondary review by the National Institute on Drug Abuse Advisory Council unless not recommended for further consideration by the initial review group. AWARD CRITERIA The anticipated date of award is September 30, 1994. Applications recommended for further consideration by the NIDA Advisory Council will be considered for funding on the basis of overall scientific and technical merit of the application as determined by peer review, appropriateness of budget estimates, program needs and balance, policy considerations, adequacy of provisions for the protection of human subjects, and availability of funds. Where appropriate, funding for the HNRC applications will also be considered on the basis of demonstrated capacity to recruit evaluable patients and submit acceptable data in appropriate time frames to permit optimal analysis of results. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Christine R. Hartel, Ph.D. National Institute on Drug Abuse 5600 Fishers Lane, Room 10A-31 Rockville, MD 20857 Telephone: (301) 443-1887 Direct inquiries regarding fiscal or grants management issues to: Gary Fleming, J.D., M.A. Grants Management Branch National Institute on Drug Abuse 5600 Fishers Lane, Room 8A-54 Rockville, MD 20857 Telephone: (301) 443-6710 AUTHORITY AND REGULATIONS This program is described in the Catalogue of Federal Domestic Assistance No. 93.279. Awards are made under authorization of the Public Health Service Act, Section 301, and administered under PHS grants policies and Federal Regulations at Title 42 CFR 52 "Grants for Research Projects," Title 45 CFR Part 74 & 92, "Administration of Grants" and 45 CFR Part 46, "Protection of Human Subjects." Title 42 CFR Part 2, "Confidentiality of Alcohol and Drug Abuse Patient Records" may also be applicable to these awards. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. .
Return to NIH Guide Main Index
Office of Extramural Research (OER) |
National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 |
Department of Health and Human Services (HHS) |
||||||||
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files. |