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American Recovery and Reinvestment Act of 2009 (Recovery Act)

Recovery Act Limited Competition for NIH Grants: Research and Research Infrastructure "Grand Opportunities" (RC2)
National Institute on Drug Abuse

The purpose of the Research and Research Infrastructure Grand Opportunities program is to support high impact ideas that lend themselves to short-term, non-renewable funding, and may lay the foundation for new fields of investigation. The program will support large-scale research projects that accelerate critical breakthroughs, early and applied research on cutting-edge technologies, and new approaches to improve the synergy and interactions among multi and interdisciplinary research teams.

This initiative is one of several being offered by IC to help fulfill the goals of the American Recovery and Reinvestment Act (ARRA) to help stimulate the economy through support of biomedical and behavioral research. Additional information the Recovery Act and related NIH opportunities is available through the Office of Extramural Research

Overall, NIDA expects to devote $40,000,000 over 2 years to the Grand Opportunity program.

Areas of Scientific Priority:

While NIDA is interested in research on all drugs of abuse, for this initiative we are particularly interested in nicotine and tobacco research. Areas of scientific interest include:

Send Letters of Intent to cite RFA-OD-09-004 in the subject line. In the letter, please state the NIDA priority area (see above list) to which the application would be responding.

General Information

Vaccines/Immunotherapies for Substance Related Disorders

Immunotherapies in the form of vaccines or antibodies are offering a window of opportunity to discover safe and effective treatments for substance-related disorders (SDR). Unlike conventional small molecule therapy, which targets the neural pathways/receptors involved in drug addiction, immunotherapy targets the drug itself through pharmacokinetic antagonism. Drug-specific antibodies bind the drug in the blood and prevent its access and distribution into the brain. The result is preventing the toxic effects of the drug to the brain or the access and stimulation of the brain reward systems by the drug. Through this RFA, NIDA is soliciting applications to expand the knowledge about the safety and efficacy of immunotherapies for SRDs. The goal is to encourage, complement, and accelerate the process of developing new, innovative, safe and effective immunotherapies for SRDs. Research topics may include 1) preclinical studies required for the IND-targeted development of immunotherapies such as design, synthesis, formulation, toxicology, and pharmacokinetics of proposed immunotherapy candidates, 2) human laboratory (Phase I) studies of the safety and preliminary efficacy of immunotherapies as well as interaction studies to evaluate the effects of immunotherapies and the concurrent use of drugs of abuse, 3) Phase II and Phase III randomized clinical trials to evaluate the safety and/or efficacy of immunotherapies for the treatment of substance use or substance-induced disorders or any of their specific symptoms. When considering the appropriateness of research projects for this RFA, it should be kept in mind that completion of all work within two years must be feasible. Interactions and relationships between academia and industry are encouraged.

Contact: Nora Chiang 301-443-5280 or 301-443-8099 or Jamie Biswas, 301-443-8096

Small Molecule Development for Substance Related Disorders

There is a great public health need to develop safe and effective medications for the treatment of drug addictions. Scientific advances in understanding the neurobiology of addictions coupled with the development of new medications and the identification of new targets offers a unique opportunity for the development of safe and effective medications to treat these disorders. Through this RFA, NIDA will support preclinical and clinical studies to evaluate the safety and efficacy of potential medications for the treatment of drug addictions. Applications may focus on the pharmacotherapy of one or various addictions with or without other comorbid medical or psychiatric conditions. Applications may also focus on pharmacotherapies for specific clinical manifestations of addictions (e.g, drug withdrawal or craving) or their complications (e.g., cognitive impairments, sleep disorders). Under this RFA, the applicants may submit FDA-defined Phase I, Phase II or Phase III clinical trials of new compounds or marketed medications that have theoretical or empirical evidence of efficacy to treat drug addictions. The rationale for choosing the medication(s) or compounds to be investigated can be based on a top-down approach, a bottom-up approach, or both approaches combined. The top-down approach would be the testing of marketed medications that are available for other indications and which may be promising candidates for the treatment of drug addiction. The bottom-up approach involves the preclinical evaluation of promising new chemical entities with a strong rationale for clinical efficacy. Preclinical projects must include the evaluation of compounds with novel mechanisms of action in addiction-related animal models and/or the completion of IND-enabling studies. When considering the appropriateness of research projects for this RFA, it should be kept in mind that completion of all work within two years must be feasible. Results from studies funded with this RFA are expected to advance the development of medications to treat drug addiction. Interactions and relationships between academia and industry are encouraged.

Contact: Nora Chiang 301-443-5280 or 301-443-8099 or Jamie Biswas, 301-443-8096

Brain Development, morphology and genetics

To generate critical information about normal brain development and the biological precursors and correlates of complex brain disorders, such as ADHD, autism, schizophrenia, and drug addiction, NIDA is interested in studies that integrate clinical, behavioral, imaging, and/or genetic assessments of brain development in humans or animal models. Specifically, NIDA will support studies that:

Conduct whole genome sequencing or genotyping and brain imaging/morphology scans on children or mouse models to provide normative data for understanding factors related to brain development, as well as to provide a reference for further addiction-specific analyses.

  • Examine genetic contributions of brain imaging and structural morphology across inbred strains of mice across developmental stages and/or exposed to drugs of abuse
  • Develop and analyze a brain atlas of gene expression in nicotine exposed mice
  • Establish a brain bank for substance use disorders (e.g. nicotine addiction) and integrate with existing brain banks around the world
  • Molecular profiling of cell types in brain regions associated with addiction and their response to addictive substances.
  • Establish and validate knockouts, knock-ins, and conditional knockouts in mice for addiction studies. Priority will be given to requests using the NIH knockout project resource ( if the requested knockout alleles are available in the resource.

Contact: Jonathan Pollock 301-435-1309 or Cheryl Boyce,, 301-443-4877


The need for accurate, reliable screens for drug exposure and vulnerability to addiction is of critical importance to substance abuse prevention and treatment. Although tests of bodily fluids or hair, and surveys using self-report questionnaires are common options, their value is compromised by their less-than-perfect reliability, low sensitivity, and limited scope. On the other hand, "peripheral" biomolecules promise to provide the type of comprehensive biological information needed to advance drug abuse research in the following areas:

  • Prevention - One challenge for prevention researchers is to develop and test emerging technologies to explicate under-explored mechanisms of neurobiological risk and to facilitate understanding of the biological and neurobiological effects of social, emotional, and behavioral preventive interventions. For example, researchers have successfully integrated measures of hypothalamic-pituitary-adrenal (HPA) axis functioning into clinical prevention research to help elucidate changes in stress hormone systems that may accompany changes in clinical studies. This FOA seeks to increase the availability of technologies that can be used in prevention trials to provide insight into biological and neurobiological mediators of drug abuse prevention interventions.
  • Treatment/Early Intervention - The ability to identify acute or chronic drug exposure will facilitate early intervention, assessment of treatment adherence, prediction of treatment response, monitoring of the recovery process, and may potentially serve as surrogates for changes taking place in the brain resulting from drug exposure, withdrawal, or relapse. For example, identification of biomarkers for nicotine addiction that are suitable for subsequent validation efforts for personalized therapies and predicting treatment response and relapse risk are of high interest.

Through this FOA, NIDA solicits applications for animal or human research to search for "peripheral" biomarkers (not the drug itself or its metabolites). The biomaterials selected must be clinically accessible (e.g., blood, lymphocytes, bladder epithelial cells, stem cells, etc.) or indirect measures such as EEG, and the proposed research should be directed at identifying the best class or classes of molecules (proteins, peptides, RNA, miRNA, etc.) suitable for assay development. The overall goal in this priority area is to address technical issues such as sensitivity and signal-to-noise ratio, in addition to predictive validity of the putative biomarkers selected and studied.

Contact: Elena Koustova 301-496-8768 or Elizabeth Ginexi (301) 402-1755 or Cecelia McNamara Spitznas,, 301-402-1488


Individual genetic variation may confer vulnerability or resistance to drug abuse and addiction. Recently developed genetic methodologies (e.g., genome wide association studies, deep sequencing) make it possible to better understand the genetic factors underlying drug abuse and addiction and their relationship to various drug abuse phenotypes. To capitalize on these advances, this FOA is requesting applications to:

  • Understand genes and biological systems involved in addiction and co-morbid disorders by:
    • Producing a unique supplementary addiction genotype array for characterizing a variety of neuropsychiatric disorders, such as addictions, depression, and schizophrenia that would compliment a standard genotype array (e.g 300K - 1M SNP arrays). This resource would allow a single standardized SNP platform to be screened for genetic variants related to substance abuse and related psychiatric disorders in existing DNA samples.
    • Conducting GWAS using existing samples collected from research grants
    • In depth data mining or meta analyses of genotypes and genomic sequencing to leverage the investment in GWAS and maximize scientific output from the analyzed datasets leveraging large-scale NIH programs to drug abuse research (e.g. applying 1000 Genomes project data to addiction genetics)
    • Deep sequencing of high priority regions associated with addiction across the genome is needed to fully understand the genomic structure, the common and rare alleles contributing to disease, and possibly establish insights to function and phenotype.
    • Long-range phasing and haplotype imputation of phenotypes associated with nicotine addiction in specific populations
    • Conducting whole genome sequencing in a well-characterized set of non-smokers and dependent smokers with and without lung cancer and chronic obstructive pulmonary disease (COPD) to develop a full functional understanding of the genomes sequenced in individuals with a highly common disease (nicotine dependence) and its mortal consequences (lung cancer and COPD). Analyses of these data will help to inform potential tailored treatments, to predict those at high risk of these diseases, and to provide important insights into understanding pathogenesis of different disease endpoints from a common exposure.
  • Conducting functional genomics studies of nicotine addiction, including:
    • Studies of bioactive molecules (e.g. non-coding RNAs, enzymes, ligands, or compounds) that interact with gene variants associated with addiction; such as genetic variants within nicotinic receptor subunit genes, genes that metabolize drugs of abuse (e.g. CYP2A6 and nicotine), and/or genes involved in the addiction process (e.g. COMT, DRDs, MAO, etc)
    • Studies to understand how specific drug exposures differentially alter gene networks in addiction
    • Studies examining in vivo gene variant effects using imaging strategies
    • Studies that use protein structure/function relationships to predict functional effects of gene variants associated with addiction phenotypes
    • Development of computational approaches that facilitate medication development of compounds targeting gene variants associated with addiction, and include infrastructure for in vitro and/or in vivo validation
    • Maping addiction associated phenotypes/traits using collaborative cross or advanced intercross strains of mice
    • Translational studies for functional genomics (animal to human)
    • High throughput assay development for functional studies of genetic and epigenetic variants that contribute to drug abuse
    • Computational methods for integrating sequence, genotype, and epigenetic data
    • Bayesian modeling for gene x gene (SNP x SNP) interactive effects, including gene x gene x environment

Contact: Joni Rutter 301-435-0298, or Jonathan Pollock 301-435-1309 or Harold Gordon,, 301-443-4877

Harmonizing Phenotypes and Envirotypes across Studies for Genomic Research on Drug Abuse

Over many years, NIDA and other NIH Institutes have funded numerous high-quality studies that contain a wealth of data (genetic, phenotypic, envirotypic) from individuals who are at risk for, or are in the course of development, progression, and desistance of, substance abuse and related phenotypes. This FOA seeks to increase the potential for comparability, replication, and pooling of data across research studies by harmonizing phenotypic and exposure measures for large-scale genome-wide association studies (GWAS) and other genomic research efforts. Applications qualifying for submission under this FOA must rely exclusively on existing studies of human subjects; funding is permitted only for the purpose of supporting the requisite labor-intensive work of harmonizing the phenotypic and envirotypic variables for genetic analyses. Contacts: Kevin P. Conway, 301-443-6504, or Joni Rutter 301-435-0298,


There is emerging evidence that epigenetic processes play a pivotal role at the fulcrum between the environment and the genome. No where is this more apparent than in the nervous system. The National Institute on Drug Abuse is very interested in the intersection of drug abuse and epigenetic research. Studies investigating one or more of the following areas are of interest:

  • The role of epigenetic changes and/or non-coding RNAs in addictive processes, co-occuring psychiatric conditions, or neuroplasticity
  • Identification and/or development of therapeutic molecules that function via modulation of epigenetic regulatory proteins
  • Identification of epigenetic or non-coding RNA signatures associated with drugs of abuse. Studies that seek to correlate brain signatures with those from readily accessible tissues such as blood.
  • Technologies that will facilitate the epigenetic analysis and profiling of heterogenous neuronal tissues
  • Technologies enabling in vivo imaging of epigenetic marks, modifying enzymes, or effector molecules in the brain
  • Studies investigating parental imprinting and contributions to allele-specific gene expression in tissues or processes relevant to addiction
  • Studies investigating transgenerational epigenetic effects of drugs of abuse
  • Integration of epigenetic measures with ongoing genetic and/or epidemiological studies, especially studies on nicotine dependence
  • Studies examining gene silencing and/or over-expression due to first-hand, second-hand, and third-hand exposure to tobacco smoke induced epigenetic modifications

Contact: John Satterlee 301-435-1020 or Steven Grant, sgrant@nida,, 301-443-8869


Pharmacogenetics research has made great strides in recent years, however, our knowledge of all genetic predictors of drug responses is far from complete and further research is needed to clearly establish genotype-phenotype relationships. NIDA is interested in applications to conduct research into understanding the genetic/genomic basis of variable drug responses, both to optimize efficacy and prevent adverse effects. The proposed research studies should include efforts not only to identify the genes, pathways, and systems that produce inter-individual differences in drug responses, but also to establish the mechanistic basis of these differences. Specifically, NIDA seeks applications:

  • To identify the variability in addiction-related genes and evaluate the functional consequences of that variability leading to clinical application of the knowledge.
  • For high-throughput studies of approved treatments for drugs of abuse in human populations that will incorporate replication studies as well as analysis of function/mechanism.
  • Using translational approaches that apply genetic knowledge with other knowledge (such as well-characterized enzymatic assays) to define, test, and validate a sensitive and specific test for success regardless of cessation method or treatment.
  • To explore drug-drug interactions (for example, drugs of abuse combined with medications, or medications for drugs of abuse combined with other medications), pharmacogenetics of safety and efficacy in phase II and III trials,
  • To develop methods for prediction of treatment success for addiction.
  • That associate responses to pharmaceutical treatments of patients with addictive disorders (or at high risk for these disorders) with genomic variation. Novel approaches, including the use of biomarkers and other component- or intermediate-based phenotypes correlated with the clinical disorder, are also encouraged.
  • Detecting low levels of metabolic changes in binge drug taking (e.g. do cotinine and 3-hydroxycotinine metabolic profiles fluctuate following episodes of acute or "power" smoking)
  • To explore HIV treatment x drug of abuse interactions (e.g. efficacy of HAART therapy in nicotine addicts)
  • Using pharmacogenetic approaches to differentiate smoking cessation genetics from smoking dependence genetics to establish gene variants associated with relapse risk and/or quit success.

Contact: Joni Rutter 301-435-0298, or Steven Grant, sgrant@nida,, 301-443-8869

Increasing the Impact of Trial Results from the NIDA Drug Abuse Treatment Clinical Trials Network

The CTN provides an enterprise in which NIDA, treatment researchers, and community-based service providers cooperatively develop, validate, refine, and deliver new treatment options to patients in community-level clinical practice. To achieve this mission, the CTN conducts studies of behavioral, pharmacological, and integrated behavioral and pharmacological treatments multi-site clinical trials to determine effectiveness across a broad range of community-based settings and diversified patient populations. These special populations include adolescents, young adults and persons at high risk for HIV and other sexually transmitted diseases. Recent trial results have indicated that behavioral and pharmacological interventions can affect drug use and other risky behaviors in adolescents or young adults, but the longer term effects of these treatments is unknown. Another area where vulnerable populations intersect, and which is under investigation at CTN, concerns the risk of HIV infection relating to drug use and subsequent behavior. The use of HIV rapid testing, counseling, and provision of test results may affect the spread of HIV; however, the usefulness and flexibility of these procedures remains to be tested in clinics that treat drug abuse clients. A current trial ongoing at CTN is proving feasible in drug abuse clinics, and expansion of this trial to include additional sites, specifically those which concentrate on STD/STI would add considerable information to NIDA's effort to treat HIV infection and drug abuse. These opportunities to augment research are time-limited.

Contact: Ron Dobbins 301-451-9575 or Mary Ellen Michel 301-435-0883

Technology to Deliver Evidence Based Practices to Criminal Justice Populations

Criminal justice settings are key domains for the implementation of effective drug abuse and drug-related HIV prevention and treatment interventions. In juvenile justice settings virtually all clients could benefit from some level of intervention - for example, primary drug and HIV prevention for those who have not started abusing drugs, and drug abuse treatment (combined with HIV prevention) for those with a drug use disorder. In adult settings, a large portion of offenders have significant histories of drug abuse or addiction; yet, treatment is often unavailable. Part of the problem is that treatment is often complicated to deliver and is provided inconsistently. One solution is to use novel technologies to address this problem. Technologies include DVD and web-based approaches to intervention delivery, use of automated systems for monitoring and tracking offenders, and new systems for tracking and implementing treatment.

This FOA will support the development and testing of novel uses of electronic and media-based technologies for delivery of the full range of drug abuse and drug-related HIV prevention interventions to juvenile and adult criminal justice populations. Topics of interest include:

  • Development of feasible and tested screening tools for juvenile and adult criminal justice settings that would efficiently and effectively identify the full range of substance abuse problems: at risk, use/abuse, and addiction, as well as HIV risk behaviors. The end products could be used in assignment to appropriate levels of intervention, whether prevention, early intervention or treatment.
  • Development and testing of technology-based interventions. These might include DVD, web-based, PDA-based or other approaches to efficiently and effectively deliver high-quality, consistent care.
  • Development and testing of technologies to assist in the management of treatment services. Key to this goal is the development of technologies which allow more efficient and effective management of information and coordination of care among multiple systems (e.g. probation/parole, courts, specialty substance treatment, employment agencies, etc.).
  • Development and testing of training materials for criminal justice personnel to encourage more widespread implementation of evidence-based practices.

Contact person: Akiva Liberman, Ph.D. 301-443-6504 or Will Aklin, Ph.D., 301-443-3207

Building Prevention Infrastructures

Even though effective substance use prevention programs have been developed and their long-term positive impact established, a small proportion of prevention service settings implement evidence-based programs, significantly limiting the public health impact of those research and development efforts. Type 2 translation research (e.g., research on factors associated with the adoption and utilization of scientifically validated interventions by service systems under controlled, uncontrolled or uncontrollable conditions) is needed to move effective drug abuse and HIV/AIDS prevention interventions into service settings. The 2009 National Research Council and Institute of Medicine report "Preventing Mental, Emotional, and Behavioral Disorders Among Young People: Progress and Possibilities" report highlights the need for "research questions related to the adoption of a prevention program into a service system, which routinely involves the formation of partnerships and the development of an infrastructure to support the technical, financial, administrative, monitoring, evaluative, and logistical needs related to the program (p.323)." Here are examples of work that needs to be completed in order to build prevention infrastructures for moving efficacious interventions into effectiveness trials and can be completed within a two-year period:

  • Developing and testing systems and models for training, assessing, and monitoring implementation.
    • Some of this work can be done online (e.g., measuring implementation and monitoring online).
  • Adapting interventions and getting feedback on them so that they can be most easily delivered within a specific system.
    • Cross-cultural adaptations (cross-cultural specific versus broad).
  • Putting interventions into modalities that are easily accessible (e.g., online, DVD).
  • Studying the needs of the deliverers and recipients of the interventions for uptakes of the interventions.
    • Social marketing, focus groups.
    • Workforce interventions
    • Providing military provider access through web-based prevention platforms
  • Economic analyses that compare highly vulnerable multi-problem youth to low and moderated risk groups embedded within universal prevention interventions to demonstrate the cost benefits for untargeted and targeted prevention interventions.

Contact: Belinda E. Sims, Ph.D. 301-402-1533

General Information

Funding Priorities

Overall, NIDA expects to devote $40,000,000 over 2 years to the Grand Opportunity program.

Key Dates

Release/Posted Date: March 20, 2009
Opening Date: April 27, 2009 (Earliest date an application may be submitted to
Letters of Intent Receipt Date(s): April 27, 2009
NOTE: On-time submission requires that applications be successfully submitted to no later than 5:00 p.m. local time (of the applicant institution/organization).
Application Due Date(s): Changed to May 29, 2009 (see NOT-OD-09-0900)
AIDS Application Due Date(s): Not applicable
Peer Review Date(s): June/July 2009
Council Review Date(s): August 2009
Earliest Anticipated Start Date(s): September 30, 2009
Additional Information To Be Available Date (Activation Date): Not Applicable
Expiration Date: May 28, 2009

Send Letters of Intent to cite RFA-OD-09-004 in the subject line. In the letter, please state the NIDA priority area (see above list) to which the application would be responding.

Contact Information

Christine Colvis, Ph.D.

SRO contact:
Teresa Levitin, Ph.D.
(301) 443-2755

Grants Management Contact(s):
Pamela G. Fleming
Phone (301) 253-8729

Additional Resources

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