National Advisory Council on Drug Abuse (NACDA) Approved Concepts

A concept describes the purpose, scope, and objectives of a potential funding opportunity. Approved concepts are usually developed into Requests for Applications (RFAs), in which funds are set aside by the Institute to stimulate a specific program of research. Concepts are being posted to give interested researchers additional time to plan for application submissions. The NACDA conducts most, but not all, NIDA concept clearances. Concepts may also be cleared through other public venues.  Concepts cleared through other public venues are marked with an asterisk (*). 

Please send questions regarding specific concepts to the program contact listed in the description. Please also note that to avoid any conflicting information, once a concept has been finalized as a published RFA (or similar funding announcement), it is deleted from this early notification, concept clearance list.

Concept Index:

Device-Based Treatments for Substance Use Disorders

Posted: May 15, 2020

Background 

There are effective pharmacological and behavioral treatments, but the long-term success rate is low and not all individuals are responsive. Moreover, approved treatments are not available for cannabis, methamphetamine and cocaine use disorders. The development of safe and effective therapeutic devices for substance use disorders (SUDs) represents an opportunity to address the significant public health need for new SUD interventions. With the approval of neuromodulatory devices for treatment of mental health disorders such as depression and obsessive-compulsive disorder, interest has rapidly grown around applying these and related technologies to SUDs. Studies examining the effects of neuromodulation on nicotine, alcohol, cocaine, and other SUDs have reported some therapeutic effects. Further work, however, is needed to strengthen and build upon these data. 

Goal 

The goal of this Funding Opportunity Announcement (FOA) is to accelerate the development of devices to treat Substance Use Disorders (SUDs). Specifically, the objective is to move devices to their next step in the FDA approval process, with the ultimate goal of generating new, FDA approved device-based treatments for SUDs. High priority areas of research include understanding the relationship between changes in brain circuitry and behavioral responses, what SUD behavioral activities are responsive, how long does the altered behavioral response last, and are subsequent treatments needed to maintain the behavioral response. The continuing advances in technologies offer unprecedented opportunities to develop neuromodulatory or neurophysiological devices that are safe and effective SUD treatments. 

Kevin Walton, Ph.D. and Will M. Aklin, Ph.D., Division of Therapeutics and Medical Consequences 


Providing Research Education Experiences to Enhance Diversity in the Next Generation of Substance Use and Addiction Scientists

Posted: May 15, 2020

Background 

Every facet of the United States scientific research enterprise—from basic research to clinical and translational research to policy formation–requires superior intellect, creativity and a wide range of skill sets and viewpoints. Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust. 

This program will provide the resources needed to assist with the preparation of individuals from diverse backgrounds to successfully transition to the subsequent professional career stage. This concept invites applications from established researchers with a record of NIH funding, who can demonstrate that they have successfully guided previous early career scientists to independent research careers and are able to direct an educational research capacity building program. This program intends to strengthen the pipeline of individuals in biomedical, behavioral, and clinical substance use and addiction research across various stages of the research pipeline to enhance the number of independently funded investigators from diverse backgrounds. It is also expected that efforts and resources from this program will foster a greater understanding of the implications of substance use and addiction nationwide and contribute to the biomedical research workforce which will help to develop solutions to reduce the burden of substance use, addiction, and their health-related consequences across all populations. 

Goal 

The overarching goal of this program is to support activities that encourage individuals underrepresented in the biomedical and behavioral sciences to pursue further studies or careers in substance use and addiction research. Specific goals include: 

  • Diversify biomedical and behavioral research scientists to ensure a cutting-edge research workforce that will advance the knowledge base needed to combat urgent substance use and addiction issues. 
  • Provide innovative, state-of-the-art, evidence-based education to undergraduate and predoctoral students, postdoctoral fellows, and/or early-stage investigators from diverse backgrounds who are equipped to pursue substance use and addiction research later in their careers. 
  • Cultivate research experiences, NIH grant application and manuscript submissions, technical training opportunities, professional development activities, formal mentoring plans, courses and seminars for skills development, and other research career fostering activities. 
  • Prepare predoctoral students, postdoctoral researchers, and/or early-stage investigators to successful transition to the subsequent career stage. 

Albert Avila, Ph.D., Office of Research Training, Diversity, and Disparities (ORTDD) 


Multi-Site Studies for System-Level Implementation of Substance Use Prevention and Treatment Services

Posted: May 15, 2020

Background 

The field of implementation science has grown substantially over the past decade. Researchers have gained fluency with implementation concepts, methods, and principles, and there has been a measurable shift from merely identifying the barriers to high quality care, to designing targeted strategies to increase the routine use of evidence-based treatment and prevention practices. However, much of the implementation research activity in the addiction field still tends to focus on strategies to deploy a specific intervention in a specific setting or population. This incremental approach to implementation research is inefficient, idiosyncratic, and slow. Meanwhile, services for alcohol, tobacco and other drugs remain inconsistent in their availability, accessibility, affordability, and quality. 

Goal 

The goal of this proposed initiative is to stimulate research focused on the development and testing of implementation strategies, models, and/or frameworks that could promote system-level uptake of evidence-based treatment and prevention interventions, guidelines, and business practices. That is to say, the initiative would call for multi-site studies designed to provide insights into how to accomplish large-scale implementation of evidence-based practices across systems of care. The goal is to address implementation on a larger, system-level scale that is more analogous to the way that policy changes can lead to state- or system-wide changes in service delivery. In so doing, research funded under this initiative would yield conceptual and practical insights that are generalizable beyond individual clinics or organizations, and inform a generalized theory of implementation of evidence-based practices for the prevention and treatment of alcohol, tobacco, and other drug problems. In practical terms, these studies should generate replicable strategies that can be used to effectively deploy guidelines, practices, and policies across entire systems of care. In conceptual terms, these studies should also leverage the multi-site platform to test implementation science hypotheses, explore novel methodological approaches, or test new measures or models that can inform future implementation research in this or other health domains. 

While the language of this concept focuses on the implementation of evidence-based practices, research on strategies to achieve system-level de-implementation of ineffective, outdated, or harmful practices would also fit within this initiative. 

Lori Ducharme, Ph.D., Division of Epidemiology, Services and Prevention Research, NIDA 


AIDS-Science Track Award for Research Transition

Posted: May 15, 2020

Background 

There is a continuing need to attract investigators into HIV-related substance use research. Common mechanisms do not easily address themselves to this goal and many investigators do not need the long-term intensive training of mentored awards or do not qualify for them because of their career stage. 

Goal 

This concept will support a wide range of early-stage HIV/drug use research. It will provide a flexible approach to support early career investigators, as well as established HIV investigators who wish to enter substance use research and established drug use investigators wishing to enter HIV research. This concept will support research in basic, clinical, treatment development, epidemiology, prevention, and services areas. Its scope will be broad including analysis of existing, small self-contained research projects, development of new methodologies and development of new research technology. The expectation is that these projects would enable investigators to begin a program of HIV/drug use research and be able to use their findings in support of full scale research projects.

Richard A. Jenkins Ph.D., Division of Epidemiology, Services and Prevention Research 


Development & Testing of Novel Interventions to improve HIV Prevention, Treatment, and Program Implementation

Posted: May 15, 2020

Background 

There is a continuing need to support research that promotes novel interventions to prevent or treat HIV among drug using populations, as well as implementation research that disseminates evidence-based practices among settings that serve this population. This work requires a mechanism that can support formative work for new interventions along with pilot trials that can answer questions such as intervention or implementation acceptability and feasibility. 

Goal 

This concept will support development and pilot testing of novel interventions to prevent or treat HIV among drug using populations, as well as related areas of implementation research. The scope of this concept will include formative research to inform development of specific intervention or implementation activities and pilot testing to examine feasibility and acceptability of these novel approaches. Successful interventions would be expected to provide evidence that the intervention or implementation strategies are ready to enter efficacy trials. 

Richard A. Jenkins Ph.D., Division of Epidemiology, Services and Prevention Research 


Population Assessment of Tobacco and Health (PATH) Study Biospecimen Access

Posted: May 15, 2020

Background 

The Family Smoking Prevention and Tobacco Control Act (FSPTCA), signed by the President in June 2009, created the FDA Center for Tobacco Products (CTP) and granted it authority to regulate the manufacture, marketing, and distribution of cigarettes, cigarette tobacco, roll-your-own tobacco, and smokeless tobacco in order to protect public health. The law also gave FDA the ability to regulate additional tobacco products, commonly referred to as “deeming” them through rulemaking. In 2016, FDA finalized a rule that extends FDA's regulatory authority to all tobacco products including electronic cigarettes or electronic nicotine delivery systems (ENDS), cigars, pipe tobacco, hookah tobacco, and other tobacco products such as nicotine gels. A full description of the FSPTCA can be found on FDA’s website. 

The PATH Study is a national cohort study designed to generate longitudinal epidemiologic data on tobacco use behaviors including patterns of use, attitudes, beliefs, exposures, and related health outcomes. The cohort is a household-based, nationally representative sample of approximately 46,000 participants. These include both youth (12 to 17 years) and adult (18 years and older) current users of a wide array of tobacco products, former tobacco product users, and nonusers. The participants were recruited from 156 geographical primary sampling units (PSUs) across the U.S. in which a PSU is a county or group of counties. The data generated by the PATH Study will contribute to the evidence base used to inform FDA’s regulatory mission under the FSPTCA. 

The PATH Study consists of four annual (Waves 1 through 4) and three biennial (Waves 5 through 7) waves of data and biospecimen collection. The first annual wave began in September 2013 and was completed in December 2014. Waves 2 through 4 began in October of 2014, October of 2015, and December of 2016, respectively, and were completed approximately one year after being started. Wave 5, the first biennial wave, began in December 2018 and concluded approximately one year later in December 2019. Wave 6 is planned to start in December 2020. The multi-wave design allows for the longitudinal assessment of the participants’ patterns of use of tobacco products, tobacco exposures, health, and risks for disease. 

Goal 

This Funding Opportunity Announcement (FOA) allows investigators to apply for access to the Population Assessment of Tobacco and Health (PATH) Study biospecimens for use in conducting tobacco-related research studies. Stored biospecimens available to researchers include urine, serum, plasma, and genomic DNA. Information about the numbers and types of biospecimens, questionnaire and biomarker data that are available to applicants is located on the PATH Study page at the NAHDAP website. Investigators proposing meritorious and feasible studies consistent with PATH Study objectives and/or research priorities for tobacco regulatory science will be given highest priority for access to PATH biospecimens. Studies that address other objectives that expand the knowledge of tobacco use and/or tobacco related health outcomes will also be considered but will be a lower priority.

Heather L. Kimmel, Ph.D., Division of Epidemiology, Services and Prevention Research 


Cutting-Edge Basic Research Awards (CEBRA)

Posted: May 15, 2020

Background 

The Cutting-Edge Basic Research Awards (CEBRA) fosters highly innovative or conceptually creative research that advances our understanding of the etiology, pathophysiology, prevention, or treatment of substance use disorders (SUDs). The CEBRA program was designed by NIDA to foster novel research approaches and represents the high priority placed by NIDA on identifying such research. NIDA’s CEBRA program supports high-risk, potentially high-impact research that is underrepresented or not included in our current portfolio. The CEBRA program seeks applications from investigators with experience in SUD-relevant research that push boundaries and/or advance knowledge through exploring new research avenues and technological advances. The CEBRA program encourages applications that explore and develop new methods, techniques or conceptual frameworks to study basic questions in this SUD research. It also encourages applications from investigators with expertise in fields other than SUDs who wish to establish innovative research programs in this area or to develop new approaches, techniques or technologies that have the potential for high-impact applications in SUD and related research. 

This concept supports projects with a strong rationale and conceptual framework, but are in the early, first stages of development where there are little or no preliminary data. The CEBRA program is not intended for large-scale undertakings or to support or supplement ongoing research. Applications submitted under this mechanism should be exploratory and novel and describe projects distinct from those supported through the traditional R01 mechanism. The research proposed in a CEBRA application should break new ground or extend previous discoveries toward new directions or applications. For the CEBRA program, "basic research" is broadly inclusive. CEBRA applications will be considered for all NIDA Divisions. 

Special features of the CEBRA include: 

  • Focus on high-risk/high impact technical or conceptual innovation
  • Review convened by NIDA 
  • Expedited funding decision 

Goal 

The National Institute on Drug Abuse (NIDA) Cutting-Edge Basic Research Award (CEBRA) is designed to foster highly innovative or conceptually creative research related to the etiology, pathophysiology, prevention, or treatment of substance use disorders (SUDs). It supports high-risk and potentially high-impact research that is underrepresented or not included in NIDA's current portfolio. The proposed research should: (1) test an innovative and significant hypothesis for which there are scant precedent or preliminary data and which, if confirmed, would transform current thinking; and/or (2) develop, and/or adapt, revolutionary techniques or methods for addiction research or that show promising future applicability to SUD research. 

Amy C. Lossie, Ph.D., Division of Neuroscience and Behavior 


Advancing Technologies to Improve Delivery of Pharmacological, Gene Editing, and Other Cargoes for HIV and SUD Mechanistic or Therapeutic Research

Posted: May 15, 2020

Background 

The development of combination Anti-retroviral therapy for HIV has transformed HIV/AIDS into a chronic disease by suppressing viral replication to undetectable levels. However, even after combination anti-retroviral therapy, HIV reservoirs remain in the gut, the immune system, and the nervous system where HIV infected CD4+ T cells, macrophages, dendritic cells and microglia may reside. Thus, no cure has been found for HIV infection and no effective vaccine for HIV exists. Current anti-retroviral therapies also have problems with drug toxicity, bioavailability, and have not been formulated for sustained release. Long term sustained delivery is needed among people with substance use disorders where compliance with an anti-retroviral therapy regiment may be problematic. To address these issues the development of improved reagents or technologies to enable targeted delivery of reagents (e.g. small molecules, biologics, gene editing reagents, etc.) to particular CNS regions or cell types is of great interest. Such delivery systems would improve our ability to monitor or manipulate HIV and SUD processes and could serve as the foundation for improved future therapeutics for HIV and/or SUD. Targeted delivery of CRISPr/CAS9 constructs, a gene editing technology, to HIV reservoirs has the potential to eradicate and cure HIV. The effectiveness of gene editing technology may be enhanced through combination with nano-formulations of anti-retroviral therapeutic agents. Such nano-formulations could potentially reduce drug toxicity, improve bioavailability, and provide vehicles for sustained delivery to the periphery and the central nervous system. Sustained delivery formulations that suppress viral expression in the blood stream may eradicate HIV transmission as effectively as a vaccine among drug abusing populations who have problems with treatment compliance. 

Goal 

This initiative focuses on the development of reagents or technologies that optimize delivery of pharmacological, gene editing, or other cargoes for treatment of HIV and SUD mechanistic or therapeutic research. 

Jonathan Pollock, Ph.D., Division of Neuroscience and Behavior 


Elucidating the Effects of ART on Neural Function in the Context of SUD

Posted: May 15, 2020 

Background 

Anti-retroviral therapy (ART) changed the course of HIV from a fatal disease to a chronic manageable illness. However, even in the presence of a dramatically suppressed viral load, symptoms of altered neuronal function remain, including neuropathic pain and milder cognitive dysfunction. Although these effects have been largely attributed to remaining virus in the brain, there is evidence that independent neurological effects caused by chronic ART treatment itself may play a role, including findings showing improvement in neurocognitive symptoms in certain stable individuals that stop ART (Robertson et al., 2007). In spite of the evidence for ART-related neurological consequences, the effects of these drugs on neural function and their underlying neurobiological mechanisms are unclear. Importantly, neuronal effects of ART are likely to be unique in individuals with substance use disorders (SUD). Because drugs of abuse target neurons, they create an altered landscape for the actions of ART. Most existing studies of the neuronal effects of ART have focused on neurotoxicity and used cell culture (e.g., Robertson et al., 2012). However, the effects on neuronal function that would underlie neurocognitive effects, pain, and neuropsychiatric symptoms (e.g., affective disorders) would be expected to be more subtle than morphological changes. Additionally, these effects need to be examined not only at the cellular level, but at circuit and network levels, using cell, brain slices and awake behaving animals. Recent advances have made available tools and technology to probe brain activity at multiple scales and can accelerate our ability to address this question. 

Goal 

The goal of this initiative is to determine the degree to which ART, as used in the treatment of HIV-1 infection, alone or in the presence of SUD, contributes to the cognitive and behavioral deficits observed under suppressed viral load. This initiative encourages research to identify the effects of ART on the structure and function of brain cells (neurons and glial), particularly when occurring in a background of chronic exposure to an abused drug (e.g., opioid, cocaine, stimulant). 

Roger Sorensen, Ph.D., Division of Neuroscience and Behavior 


Combining the best technologies and latest science to decrease stigma of substance use disorders

Posted: February 4, 2020

Background 

Substance use Disorders (SUDs) are highly stigmatized worldwide, and, as a result, many people are reluctant to disclose, or even talk about it. This stigma results in patients not having access to treatment or the ability to receive adequate care. In the United States, it wasn’t until the adoption of the Patient Protection and Affordable Care Act in 2014 that health care providers were able to offer and be reimbursed for treatment services for SUD. However, despite the gains, only 11% of patients that meet the criteria for diagnosis of SUD receive treatment. A recent study, for example, reported how out of 709 participants, the majority had strong stigma against people with SUD. The results also included 78% of respondents indicating that they would not be willing to work closely with a person suffering from SUD and 64% stating that employees should be able to deny employment to people with SUD. Roughly three in 10 believed that recovery from SUD was impossible. 

Goal 

The goal of this proposed RFA is to leverage breakthrough technologies and the latest science to develop and commercialize products and services aimed at reducing stigma around SUD. 

It is expected that applications will propose the (1) latest technology; (2) evidence-based science; and (3) methods to demonstrate that the stigma to SUD will be reduced. 

Area of Specific Interest: 

  • Applications targeting stigma of SUD in adolescent population 
  • Applications providing anti-stigma training for medical professionals 
  • Applications proposing solutions to be used by non-medical providers (social workers, criminal justice, family members, and educators) 

Technologies or approaches may include, but not limited to: 

  • Neuromarketing tools (e.g., electroencephalography) and services to help develop and disseminate the most effective anti-stigma campaigns 
  • Digital compassion (anti-stigma) coaching for medical professionals delivering treatment to patients with SUD 
  • Certification program for nonprofessional care givers who provide support services for patients with SUD 

Leonardo Angelone, Ph.D., Office of Translational Initiatives and Program innovations 


Technologies for high throughput detection of opioids illegally circulating through mail 

Posted: February 4, 2020

Background

More than 70,000 Americans died from drug overdoses in 2017, some 28,000 of which were caused by fentanyl or other synthetic opioids. Hundreds of millions of dollars worth of synthetic opioids is pouring into the United States. Customs and Border Protection continue to seize large volumes of opioids (e.g. nearly 1,500 pounds of fentanyl during fiscal year 2017). However, as reported, large seizures in volume smuggled across the border typically contain low, around 7%, purity opioids. Conversely, much smaller packages but containing closer to 100% pure fentanyl come through international and domestic mail and package deliveries. Indeed, drug seizures by USPS’ Postal Inspection Service (USPIS) have been on the rise since 2014. The Service’s narcotics program seized more than 18 metric tons of illicit drugs during 2017, according to a September 2018 Inspector General report (SAT-AR-18-002) on the use of USPS for drug distribution. Between 2017 and 2018, USPS saw a 10-fold increase in international parcel seizures and an 8-fold increase in domestic parcel seizures related to opioids, including fentanyl. Currently, agencies have high demand for new opioid detection technologies that may provide efficient high throughput screening for opioids and cut the opioid supply chain. 

Goal 

The goal of this FOA is to provide opportunities for small business companies to: 

  1. develop novel approaches for rapid, nonintrusive detection tools and data analysis that will help find illicit opioids being trafficked through mail;
  2. Test feasibility of the high throughput screening of opioids in the mail;
  3. Validate usability, efficiency and of cost-effectiveness of novel developed systems. 

Because of the targeted nature of this emerging field applicants should consider working closely with the potential purchasers. 

Irina Sazonova, Ph.D., Office of Translational Initiatives and Program Innovations 


Tools for Germline Gene Editing in Marmosets

Posted: February 4, 2020

Background

The common marmoset (Callithrix jacchus) is a powerful emerging non-human primate model organism that exhibits strong potential to be used to dissect the genetic bases of key behaviors and phenotypes associated with neurological and psychiatric diseases. Marmosets are small new world monkeys that exhibit similar behaviors to humans. Females typically give birth to two litters a year and twins are common. The short gestation period and ability to produce multiple litters per year provides a distinct genetic advantage over other common non-human primate species for development of strong gene editing and transgenic technologies. In addition, proof of concept studies have demonstrated that gene editing and/or transgenic technologies are able to modify the marmoset germline. However, these gene editing technologies are in their infancy and need significant optimization to support the breadth of studies needed to uncover the biological bases of these key neurological and psychiatric behaviors in non-human primates. 

Although brain-specific gene editing and transgenic studies in rodents have been widely successful, there are distinct differences in anatomy, physiology and cognition between rodents and primates that cannot be captured in these model systems. The common marmoset is a unique non-human primate that is strongly positioned for genetic studies examining the brain. However, gene editing tools need to be developed, refined and optimized in order for the marmoset to reach its full potential as a model system to uncover the functions of circuits and cell types underlying neurological diseases and aberrant behaviors. 

Goal 

The focus of this concept is to develop tools and technologies to establish the marmoset as a non-human primate genetic model system for studying all aspects of neuroscience, including neurological diseases and conditions; aging; mental health diseases; and behaviors associated with substance use disorders. Specific goals include: 

  • Developing efficient and cost-effective strategies to routinely conduct transgenic studies and germ line editing in the common marmoset 
  • Optimizing strategies for all aspects of technologies to support production of transgenic animals 
  • Establishing and improving ovarian stimulation protocols and culture conditions 
  • Determining optimal conditions for fertilization and development of pre-implantation embryos 
  • Standardizing and optimizing semen collection, freezing, and quality assessment 
  • Developing gene editing tools for marmosets, including guide RNAs based on emerging genome drafts and annotation, tools and constructs for cell-specific analyses, and infrastructure to support the collection and distribution of these resources 

Amy C. Lossie, Ph.D., Division of Neuroscience and Behavior 


NIDA Core "Center of Excellence" Grant Program

Posted: February 4, 2020

Background

NIDA is interested in continuing our grant program seeking Research Centers of Excellence. These centers are intended to provide resources that allow researchers who currently research substance use disorders and addiction to establish core resources that create synergy to advance research. Centers are highly collaborative, provide efficiencies both in cost and scientific value by having cores that can serve many investigator, and often provide small pilot grants to support junior investigators. 

Goal 

NIDA Core Center of Excellence Grant Program is intended to bring together investigators currently funded by NIH or other Federal or non-Federal sources, to enhance the effectiveness of existing research and also to extend the focus of research to drug abuse and addiction. It is expected that a Center will transform knowledge in the sciences it is studying. Incremental work should not be the focus of Center activities; rather, new and creative directions are encouraged. Centers of Excellence are expected to integrate and promote research in existing funded projects, to achieve new and creative directions. It is expected that individual core activities reflect a relationship to the integrating theme of the Center and the Center is expected to provide research opportunities and experiences to new investigators, and share findings, data and their resources, consistent with achieving the goals of the program. 

Roger Little, Ph.D., Division of Neuroscience and Behavior 


Elucidation of mechanisms underlying complex morbidities of SUD and other mental illnesses in people living with HIV

Posted: February 4, 2020

Background

There is substantial evidence that having a SUD increases the risk for acquiring and transmitting HIV, and in PLWHIV reduces compliance and efficacy of ART. With the brain, substances such as methamphetamine can disinhibit HIV expression in previously latent reservoirs. Parallel research has shown similar effects associated with co-occurrence of other psychiatric disorders. The clinical reality, however, is that occurrence of substance use disorders (SUD) and non-SUD psychiatric illnesses is common in PLWHIV and, in fact, most people living with both HIV and SUD (PLWHIV-SUD) have an additional co-occurring psychiatric disorder. Yet there is a paucity of research on the mechanisms underlying complex psychiatric morbidity affecting this large population of PLWHIV-SUD. There is a great need to characterize neurobehavioral mechanisms underlying the psychopathology of SUD with co-occurring psychiatric illnesses in PLWHIV and determine how key neurobehavioral processes interact with HIV and ART, and ultimately impact HIV expression and AIDS-related morbidities, HIV-associated neurocognitive disorders, and/or efficacy and adverse effects of ART. 

Goal 

The goal of this program would be to support research on neurobehavioral (including neurocognitive and neuroaffective) mechanisms underlying the psychopathology involved in SUD and co-occurring psychiatric disorders in people living with HIV (PLWHIV). Major objectives would include the characterization of neuro-cognitive and -affective processes that 1) impact the risk for HIV transmission or the acquisition or maintenance of ART and psychiatric treatment, 2) interact with HIV and/or ART to impact neurocognitive function and overall psychiatric morbidity in PLWHIV. 

Given how little is known about the interactive effects of HIV, SUD and additional psychiatric morbidities on neurocognitive and neuroaffective function, there is a need to support projects incorporating conceptually-strong exploratory studies. Multidisciplinary research employing complementary approaches in elucidating neural circuit – behavior patterns in PLWHIV-SUD would be particularly impactful. Indeed the most compelling projects supported by this program would be expected to involve interdisciplinary teams with the expertise in clinical phenomenology and treatment of PLWHIV-SUD and psychiatric morbidity associated with HIV; behavioral, cognitive, and affective neuroscience; and imaging and manipulation of neural circuits where appropriate. 

Examples of questions that would be addressed by the research supported by this program include. 1) How do neurocognitive processes differ across groups varying in HIV status, SUD history and relevant domains of psychopathology? 2) How do HIV or ART interact with SUD-relevant neurobehavioral abnormalities and/or drug exposure in impact neurocognitive function in PLWHIV? 3) What are potential neurobehavioral factors that may inform about the efficacy of ART or inform treatment strategies for SUD with comorbid psychiatric conditions in PLWHIV? 4) Are their neural circuits or specific neurocognitive/neuroaffective processes that are differentially vulnerable to the effects of HIV infection or ART? How is that affected by drug taking? 

Holly Moore, Ph.D., Division of Neuroscience and Behavior 


Extracellular RNA carrier subclasses in processes relevant to substance use disorders (SUDs) or HIV infection

Posted: February 4, 2020

Background

Circulating extracellular RNAs (exRNAs) can function both systematically and locally in intercellular communication. ExRNAs may be transported in body fluids via carrier vehicles such as extracellular vesicles (EVs), ribonucleoproteins (RNPs), and lipoproteins (LPPs). These distinct carriers protect exRNAs from degradation and are thought to contribute to the biodistribution, uptake, and functional impact of exRNAs in target cells. EVs and other exRNA carriers may interact with specific cell types to deliver nucleic acid, protein, lipid, or other cargoes to alter cellular phenotypes. ExRNA carriers from body fluids such as blood, cerebrospinal fluid, urine, saliva, semen, breast milk, and amniotic fluid may provide useful biomarkers for a variety of human diseases including CNS disorders. Also, exRNA carriers may be useful for in vivo targeting of cargoes such as nucleic acids or small molecules of therapeutic value to specific organs or cell types. 

In the nervous system, EVs can function in neuronal-glial communication, synaptic plasticity, immune surveillance, or as endocannabinoid carriers. However, the role of EVs and other exRNA carriers in CNS disorders and SUDs have not been well characterized mechanistically. Understanding exRNA carrier dynamics and cargoes across the trajectory of addiction may help to identify useful biomarkers for diagnosing: 1) drug use history (the type, quantity, and/or frequency of drug use), 2) the stage/trajectory of addiction (e.g. escalation, withdrawal, incubation, craving, relapse), or 3) both. 

Some viruses are known to exploit the endogenous EV machinery during budding and infection. However, the extent to which EVs, other exRNA carriers, or host cellular machinery involved in exRNA carrier biogenesis and function may contribute to HIV infection, latency, or pathogenesis in the CNS is not fully understood. 

Goal

The goal is to encourage research investigating the roles of exRNA carrier subclasses in biological processes relevant to SUDs or HIV infection, latency, or pathogenesis in the CNS. Applicants could propose to investigate biological mechanisms involving exRNA carrier subclasses, or propose to develop improved technologies to understand extracellular vesicles or other exRNA carriers. 

John Satterlee, Ph.D., Division of Neuroscience and Behavior 


Intervention Research to Improve Native American Health

Posted: February 4, 2020

Background

Existing data indicate that significant disease inequities exist for Native American (NA) populations. Concurrently, NA populations experience unique sociopolitical, historical, and environmental stressors and risks that may exacerbate health conditions and/or impact the effectiveness of existing solutions to address the conditions. They also possess unique strengths and resiliencies that can mitigate stressors or inform intervention strategies. In addition, according to the National Congress of American Indians, Native communities prioritize research that benefits native people by informing strategies to attain health equity, such as intervention research. 

In response to listening sessions with Native communities, in 2011 the National Cancer Institute launched a trans-NIH program, titled Intervention Research to Improve Native American Health (IRINAH). Forty-one grants have been funded through IRINAH, including 8 funded by NIDA, the most funded by a single institute. For its reissuance, NCI has asked NIDA to lead this trans-NIH FOA, given the high priority placed on substance abuse research by tribal leaders and NIDA’s active participation in this funding program. While previous funding from IRINAH is doing much to advance knowledge, Native American intervention research remains a major scientific gap area across the NIH. For the purposes of this FOA, NAs include: Alaska Natives, American Indians (whose ancestral lands fall at least partially within the U.S. mainland border), and Native Hawaiians. 

Goal 

The broad purpose of this funding opportunity announcement (FOA) is to support research to improve health in Native American (NA) populations through interventions. This includes 1) etiologic research, where there is a significant gap in knowledge, that will directly inform intervention development or adaptations, 2) research that develops, adapts, and tests the efficacy or effectiveness of health promotion and disease prevention interventions, 3) research that tests culturally informed treatment interventions and 4) where a sufficient body of knowledge on intervention efficacy exists, research on the dissemination and implementation of interventions. Through this initiative, intervention and related research is sought to build upon community knowledge, resources, and resilience to test science-based, culturally appropriate solutions to reduce morbidity and mortality through identification and remediation of precursors to diseases and disorders and through culturally informed treatment. 

Specific to NIDA, language in the FOA will indicate a focus on culturally appropriate research on substance use among Native American adolescents and adults. Applications may include piloting or testing novel prevention, screening, and treatment interventions, focus on a range of topics such as etiological factors; intervention; examining patterns of health service utilization; examining treatment work force factors; and studying adaptation, implementation, and dissemination of existing evidence-based prevention or treatment interventions to increase uptake. 

Kathy Etz, Ph.D., Division of Epidemiology, Prevention and Services Research 


Evaluation and Implementation of Clinical Care Guidelines for Pain Management and Opioid-Associated Consequences

Posted: February 4, 2020

Background

In the current opioid epidemic, 50 million Americans suffer from chronic daily pain, defined as persistent or recurring pain lasting longer than 3 months. At the same time, over 2 million individuals meet DSM-5 criteria for an opioid use disorder (OUD), many who started on prescription opioid drugs before transitioning to illicit opioids. Adequate clinical care for pain management and opioid misuse/dependence faces many challenges, with a prominent gap in the education and training of the current healthcare workforce on complex comorbidities. While the estimates of training vary across disciplines, the average time devoted to pain education is 35 hours and even less time is devoted to OUD education. Pain presents itself in every health care setting, but the absence of this specialized knowledge leads to fragmented care and/or patient loss as they navigate the healthcare system to balance pain management against opioid related health consequences. 

To address the current opioid epidemic, better education and training of clinicians on pain management is crucial. As a way to achieve this goal, various federal agencies and organizations have issued prescribing and other clinical guidelines for management of acute and chronic pain, while minimizing opioid-associated adverse events, such as respiratory depression and fatal overdoses. These guidelines have helped decrease opioid prescribing rates and improve prescribing behaviors in many cases. However, in some cases, health care professionals have stopped prescribing opioids when continued opioid use may have been appropriate, resulting in other unintended consequences, such as improper pain management, suicide, and cessation of health care utilization for other associated illnesses. Balanced assessments of the associated harms and benefits of opioid analgesics for proper pain management is needed, and can be conveyed to health care providers through training and education provided within their health care system. Furthermore, in order to observe significant and sustainable changes in opioid misuse/dependence and pain management from a public health perspective, prescribing behavior must change on a systems level. However, the impact of these training approaches on the timely adherence to clinical guidelines, patient outcomes, and systems-level change have not been well studied. 

Goal 

The goal of this initiative is to evaluate how training based on prescribing and/or clinical guidelines can improve balanced assessment of pain management against opioid related health risks and benefits, and determine how best to scale up clinical behavioral change on a health systems level. Evaluation of the guideline-based training should measure changes in clinician behavior and patient outcomes. To ensure system level change in managing comorbid pain and opioid misuse/dependence, implementation success of the guideline-based educational intervention will be measured across a minimum of 5 geographically distinct sites. 

Shelley Su, Ph.D., and Lori Ducharme, Ph.D., Division of Epidemiology, Services and Prevention Research 


NIDA Dissertation Award in Substance Use and Substance Use Disorder Research

Posted: February 4, 2020

Background

NIDA is interested in continuing our grant program seeking Dissertation Award in Substance Use and Substance Use Disorder Research. This program aims to provide students with support to perform dissertation research on a topic related to NIDA’s mission, including: the study of basic and clinical, developmental, epidemiology, prevention, genetics, treatment, services, HIV, or women and sex/gender differences, and thereby increase the pool of highly talented substance use/substance use disorder scientists who conduct research in these areas. 

Goal 

This initiative seeks to help individuals obtain the necessary qualifications at the doctoral-level with an intent to subsequently establish and lead a research program in NIDA-relevant fields. This Dissertation Award provides support to complete dissertation research and includes funds that may not be readily or sufficiently available in National Research Service Awards predoctoral programs, which limit support to stipends, tuition and fees, and institutional allowance. Applications are encouraged from doctoral candidates in a variety of academic disciplines and programs. Individuals from underrepresented backgrounds are particularly encouraged to apply. This program will ultimately facilitate the entry of promising new investigators into the field of substance use/substance use disorder research and promote transdisciplinary collaborations. 

Michele L. Rankin, Ph.D., Office of Research Training, Division of Extramural Research 


NIDA Institutional Mentored Clinical Scientist Development Program Award in Substance Use and Substance Use Disorder Research

Posted: February 4, 2020

Background

NIDA is interested in continuing our grant program seeking Institutional Mentored Clinical Scientist Development Program Award in Substance Use/Substance Use Disorder Research. The purpose of this initiative is to encourage institutions to develop and/or sustain programs that support intensive, mentored research training and career development experiences for clinician scientists to support them as they advance towards research independence and develop their own independent research programs in substance use/substance use disorder research.

Goal

The goal of Mentored Clinical Scientist Development Programs is to provide clinicians with the necessary research skills and career development experiences to enable them to pursue careers in research and lead independent research programs in substance use/substance use disorder research. Clinician scientists may include (but are not limited to) physicians, clinical psychologists, epidemiologists, doctoral level social workers, pharmacists, and behavioral scientists. Programs should include both didactic training and supervised research experiences designed to accommodate research candidates with varying levels of experience and at various stages of their career. Upon completion of the program, candidates are expected to be prepared to apply for independent research funding.

Michele L. Rankin, Ph.D., Office of Research Training, Division of Extramural Research 


HEALthy Brain and Child Development Study

Posted: February 4, 2020

Background

The last twenty years has seen a tremendous increase in the number of babies born with neonatal opioid withdrawal syndrome (NOWS); recent evidence suggests that children who are born with NOWS may be at increased risk of developmental delays. However, the developmental trajectory of children exposed in utero to opioids and other harmful substances has not been systematically studied. Most studies of prenatal substance exposure only follow children for 1-2 years; therefore, very little is known about longer term outcomes, particularly as children reach school age. The HBCD Study intends to examine the influence of prenatal drug exposure and the effects of other environmental exposures on neurodevelopment. These studies will also monitor the factors that may exacerbate the negative effects of stressful environments such as food and housing insecurity, exposure to violence, and neglect. Given emerging evidence about the importance of early developmental windows on later disease, a detailed understanding of normative early brain development, as well as identifying the effects of specific insults and protective factors—classified both temporally and by type— promises to provide opportunities to identify effective interventions to improve both childhood and later adult health. The HBCD Study is designed to look at earlier exposures that could influence developmental trajectories, with an emphasis on prenatal exposure to substances and the environment in which that occurs. The large amount of expected data from the study will be available to the scientific community for analysis and should contribute significantly to our understanding of neurodevelopment. We anticipate the findings will inform and direct actions that will help educators, parents, policymakers and health professionals to improve the lives of all children.

Goal

The goal of this project is to understand how fetal drug exposure (e.g., prenatal opioid use) and adverse environmental exposures (parental neglect, physical abuse, secondary drug exposures) affect brain development and health outcomes; how these exposures impact risk for subsequent substance use and mental illness; and to inform appropriate intervention and prevention strategies. A large and growing body of evidence indicates that early exposure to substances, including pre- or perinatally, is linked to greater risk for developing substance use disorders, in addition to multiple other health and behavioral problems, including ADHD, conduct disorder, anxiety, etc. However, a causal link is difficult to establish due to confounding factors such as socioeconomic, environmental, and genetic influences. To disentangle the many factors that underlie these associations, we propose to establish a large pregnancy cohort (~ 7,500) from regions of the country significantly impacted by the opioid crisis and follow them and their children for 10 years. We propose collecting data in the following domains: fetal ultrasound; postnatal structural and functional MRI, EEG and fNIRS; anthropometrics; medical history; family history; biospecimens; and actigraphy. The cohort will include non-exposed children to establish normative brain and behavioral development trajectories for socioeconomically and environmentally matched children, to which altered trajectories can be compared. This prospective approach will allow us to investigate prodromal changes in brain and behavioral development resulting from early exposure to opioids, other substances, and associated adverse conditions that might predict emergence of, or resilience to, substance use disorders and other mental illnesses that affect health outcomes.

Michelle Freund, Ph.D., Division of Extramural Research 


The NIH Developmental Studies Biospecimen Access Program

Posted: February 4, 2020

Background

The Adolescent Brain Cognitive Development (ABCD) Study is the largest longitudinal study of brain development and child health collecting data from nearly 12,000 children across the U.S. beginning when they are 9-10 years old and continuing for a decade. In addition to behavioral assessments, youth undergo neuroimaging and provide biospecimens, including saliva for hormone analysis, urine and hair for substance use and exposure, deciduous teeth for environmental exposure, and blood for genetic analysis and metabolic and hematologic assays. 

The recently launched HEALthy Brain and Child Development (HBCD) Study will expand upon ABCD with a similar longitudinal study of brain, cognitive, and behavioral development of children from the perinatal period through 9-10 years of age. The HBCD Study, currently in the planning stage, is expected to include neuroimaging, genotyping and/or sequencing, behavioral and cognitive development assessments, and the collection of a wide range of biospecimens such as placenta, meconium, breastmilk, blood, urine, feces, and more. 

The ABCD study is in its fourth year of data collection. Currently, the ABCD study has collected approximately 1,000 whole blood samples, 2,000 serum samples, 13,000 deciduous teeth, 20,000 saliva samples and 15,000 DNA samples. As the ABCD and HBCD studies continue, the volume and variety of available biospecimens will become a significant scientific resource. 

Goal

The goal of this program is to maximize the scientific potential of the biospecimens collected in the ABCD and HBCD studies. Modeled after the Population Assessment of Tobacco and Health (PATH) Biospecimen Access Program, the NIH Developmental Studies Biospecimen Access Program will provide available biospecimens from the ABCD and HBCD studies to qualified researchers proposing meritorious and feasible studies consistent with ABCD or HBCD Study objectives or which expand the knowledge of child or adolescent health more broadly. Investigators granted access to these specimens will be required to submit their derived data to the NIMH Data Archive, making it available to the broader scientific community. This program will expand the scope of ABCD’s open science model, allowing scientists from around the world to utilize these specimens and enrich the child and adolescent health data being obtained from the ABCD and HBCD studies. 

Kimberly LeBlanc, Ph.D, Office of Trans-NIH Initiatives, Division of Extramural Research 


Avenir Award Program for Research on Substance Abuse and HIV/AIDS 

Posted: September 9, 2019

Background

This concept request is for reissue of the NIDA DP2 program in HIV/AIDS research. The Avenir Award Program for Research on Substance Abuse and HIV/AIDS supports creative individuals who wish to pursue innovative research at the nexus of substance abuse and HIV/AIDS. The Avenir award is designed to complement the NIDA Avant-Garde award by focusing on early stage investigators. Avenir applicants may propose research in any area of high priority HIV/AIDS research that has the potential to open new areas of HIV/AIDS research and/or lead to new avenues for treatment and prevention of HIV/AIDS among substance abusers. 

Goal 

The program invites applications proposing innovative approaches in basic and clinical research areas, which have the potential to benefit substance using populations with or at risk for HIV/AIDS by reducing HIV incidence, improving therapies for HIV, reducing the impact of comorbid conditions, and ultimately, eradicating HIV. Examples of studies of relevance to drug abuse include: studies using populations with significant numbers of drug users or samples from drug using populations; studies using in vitro systems and/or animal models that test the effects of drugs of abuse on HIV pathogenesis, progression, or treatment; and studies to develop interventions or treatments that are tailored to substance using populations. The award will support those in an early stage of their career who may lack the preliminary data required for an R01 grant, but who propose high priority, high impact research, and who show promise of being tomorrow's leaders in the field. 

Redonna Chandler, Ph.D., AIDS Research Program 


Ending the Epidemic: New Models of Integrated HIV/AIDS, Addiction, and Primary Care Services 

Posted: September 9, 2019

Background 

HIV/AIDS, substance use disorders, mental health conditions, and other health conditions are all highly comorbid. Currently, these services are often delivered in multiple care settings, resulting in fragmented, uncoordinated care, which contributes to suboptimal treatment outcomes. The initiative would support the development of new models of care that function as one-stop-shops capable of integrating comprehensive services, including (but not limited to) HIV/AIDS services, addiction prevention and treatment services, and primary care services. 

Goal 

The goal of this FOA is to develop and test replicable, scalable organizational and systems level interventions to determine how best to provide comprehensive, integrated interventions to improve the health outcomes related to HIV and SUD. 

Applications to this FOA will be required to utilize implementation science informed approaches, with an emphasis on scalability, replicability, quality measurement, sustainability, and cost-effectiveness. Specifically, this initiative would support: (1) care models that integrate HIV screening, prevention, and engagement in care in substance use or primary care settings; or (2) care models that integrate substance use screening, prevention, and treatment in Ryan White Clinics or other HIV Services settings, including prevention-oriented settings such as STI clinics. Applicants will be strongly encouraged to develop models that provide comprehensive care across the full prevention to treatment continuum for both HIV/AIDS and substance use supports. For HIV/AIDS, this means treatment models should include screening, PrEP, and HAART. For substance use, this means care models that include screening, prevention services, and referral to pharmacotherapies as appropriate (e.g., all three FDA-approved MOUDs). 

This effort will be aligned with the Ending the AIDS Epidemic by 2030 initiative; therefore applications to this FOA will be geographically limited to CDC’s list of vulnerable counties and jurisdictions experiencing or at-risk of outbreaks. 

Minnjuan W. Flournoy Floyd, PhD, Division of Epidemiology, Services and Prevention Research 


HIV Pathology and Latency Studies Using Live Functional Behaving Human Cell Chimera Animal Brains 

Posted: September 9, 2019

Background 

HIV can be incorporated into host cell genomes after infecting the human brain. Even with constant combined antiretroviral therapy (cART) many infected brain cells, particularly microglia, can carry latent HIV virus and become a reservoir of the virus, with consequences of persistent neuropathology. Many HIV patients are also high-risk populations of licit and illicit drug users. The commonly abused drugs such as opioids, cannabinoids, methamphetamine, and nicotine target the CNS, impact neural circuit activities and neuroimmune systems. Comorbidity of substance use disorders and HIV persistence exacerbate the brain and cognitive disorders. The cellular and molecular mechanisms of how HIV enters or reactivates from latent phase in the presence of cART and abused substances in the brain, as well as the comorbid effects, are not well understood. Since HIV does not infect non-human cells, experimenting HIV infection and latency in functional live brains has been problematic using most animal models. 

Recent technical advancements have enabled generating human-mice chimeric brains by engrafting human iPSC-derived primitive neural progenitor cells and/or cord blood-derived microglial progenitor cells into neonatal mouse. In the chimeric brain, human neural progenitor cells or microglial cells differentiate and migrate throughout the mouse brain. Such successes provide opportunities to define the structure, function, genetics and plasticity of neural networks containing human tissue. It can also serve as a rodent model to study HIV infectivity, reservoir formation, and the neuropathogenesis of HIV infection. It can also allow the study of HIV and substance abuse comorbidity in the brain of a fully functional, awake, behaving animal from the single cell to neural circuitry levels. 

Goals 

  • Foster the development of using a chimeric rodent model to advance the studies of HIV virology and latency. 
  • Study HIV neuropathology and its comorbidity with SUD, and their impacts to human neurons, glia and microglia in a fully functional, awake, behaving animal from single cell to neural circuits levels, to behavior. 
  • Provide resources for optimizing and validating the chimera models for HIV studies and its eradication. 

Da-Yu Wu, Ph.D., Division of Neuroscience and Behavior 


Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose

Posted: September 9, 2019

Background

Given the current opioid use and overdose crisis in the country, there is an urgent need to develop safer and more efficacious medications to treat opioid use disorders and overdose. This FOA was issued as RFA-DA-19-002 as part of the HEAL initiative and has been very successful in supporting the development of medications to treat those conditions.

Goal

The purpose of this FOA is to continue supporting research that accelerates the discovery and development of medications to prevent and treat opioid use disorders (OUD) and overdose. The goal is to advance medications closer to FDA approval. Applications may include preclinical or clinical research studies of small molecules or biologics that will have high impact and quickly yield the necessary results to advance closer to FDA approval medications that are safe and effective to prevent and treat OUDs and overdose.

Iván D. Montoya, M.D., M.P.H., Division of Therapeutics and Medical Consequences 


Targeting Inflammasomes in Drug Abuse and HIV

Posted: February 15, 2019

Background

Neuroinflammation triggered by brain trauma, neurodegenerative diseases or other neurotoxicant-induced central nervous system (CNS) disorders including human immunodeficiency virus type-1 (HIV-1) infection initiates CNS innate immune responses.  HIV-1 penetrates the blood brain barrier, infects macrophages and microglial cells, and promotes a cascade of inflammatory responses including the formation of inflammasomes.

Inflammasomes are a complex of high molecular weight proteins within the cytosol of stimulated cells that mediate the activation of inflammatory cascades. In response to insults, Nod-like receptors (NLRs) recruit adaptor proteins and caspase-1 to assemble inflammasomes and process the release of pro-inflammatory cytokines IL-1b, IL-18 and IL-33. The NLRP3 inflammasomes are the most well-characterized that comprises NLRP3, apoptosis-associated speck-like (ASC) adapter protein, and the downstream effector protease procasepase-1.

Recent evidence suggests that chronic drug exposure, i.e., cocaine, methamphetamine and morphine, can induce inflammasome activation primarily mediated by NLRP3 within microglia. Additionally, emerging data suggest that HIV-1 infection can also prime inflammasome activation. Drug abuse, especially in association with HIV-1 infection, induces reactive oxygen species (ROS) production, impairs blood brain barrier integrity, and promotes monocyte transmigration. These upstream events exert synergistic effects that prime oligomerization and activation of inflammasome and release of pro-inflammatory cytokine IL-1b. Persistent inflammatory signaling pathways involved inflammasome formation and activation may lead to progressive loss of the functional capacity of the immune system. This could contribute to the pathogenesis that underlies HIV-associated neurocognitive disorders (HAND).

Goal

The scientific objective of this research is to delineate the role of inflammasomes in neuropathology produced by chronic drug exposure and HIV infection. Understanding the involvement of inflammasome in the immune activation may help identify molecular markers and CNS immune cells associated with HIV-1 infection or disease progression among substance abuse populations, as well as identify novel therapies to target inflammasome activation or suppression to treat neuroinflammation and immune dysregulation aroused in these processes.

Anne Tsai, Ph.D. Division of Neuroscience and Behavior