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:

In Vitro Metabolism and Non-Clinical ADME Studies

Posted: September 14, 2020

Background

The Division of Therapeutics and Medical Consequences (DTMC) supports the development of medications for the treatment of substance use disorders (SUDs). These efforts include compound syntheses, bioanalytical chemistry, pharmacology, toxicology, pharmacokinetics/metabolism, and clinical evaluations of potential treatment medications. 

In vitro metabolism studies allow for the investigation of interspecies variations in metabolism that will help inform the selection of relevant animal models for preclinical evaluations of efficacy and toxicity; aid in the determination of metabolic pathways; identify major metabolites; and assess whether drug metabolism may be affected by genetic polymorphisms. In vitro permeability studies allow for the evaluation of a drug candidate’s ability to pass through biological membranes and to identify any transporters involved in its absorption across or efflux from the interior of these barriers. Compounds exhibiting favorable in vitro properties are advanced to non-clinical in vivo animal models to determine absorption, distribution, metabolism, and elimination (ADME) properties, as well as to evaluate potential toxicity. These models are necessary to assess the compound’s bioavailability, the concentration of compound and/or metabolites versus time in the systemic circulation, the distribution of compound and/or metabolites into tissues, and its mode of elimination. These parameters are critical data on the pathway to approval for first-in-human clinical trials. 

Goal

The objective of this initiative is to carry out in vitro metabolism and permeability and in vivo ADME studies to support the medications development program of the National Institute on Drug Abuse (NIDA). NIDA and NIDA sponsored investigators will use the data obtained for submissions to the Food and Drug Administration (FDA) in support of Investigational New Drugs (INDs) and New Drug Applications (NDAs). 

Jason Sousa, Ph.D., Division of Therapeutics and medical Consequences


NIDA Translational Avant-Garde Award for Development of Medication to Treat Substance Use Disorders

Posted: September 14, 2020

Background

The purpose of this initiative is to support outstanding basic and/or clinical researchers with the vision and expertise to translate research discoveries into medications for the treatment of Substance Use Disorders (SUDs) stemming from tobacco, cannabis, cocaine, methamphetamine, heroin, or prescription opiate use disorders.

Through this initiative, NIDA seeks to attract exceptionally talented investigators to the mission of expanding the number and breadth of lead molecules in the pipeline for drug addiction treatment, optimizing these leads, and/or advancing them to clinical testing.

Eligible applicants must demonstrate the ability to develop molecules with the potential to treat SUDs and advance them in the drug development continuum. The ultimate goal of this initiative is to bring molecules closer to FDA approval.

Goal

To support outstanding investigators who can lead the development of medications through the FDA pathway of approvals with the ultimate goal of expanding the armamentarium of safe, effective and marketed medications to treat SUDs.

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


Exploratory Studies to Understand Mechanisms of HIV Infection, Replication, Latency, and/or Pathogenesis (Including HAND) in the Context of Substance Use and Substance Use Disorders (SUD)

Posted: September 14, 2020

Background

Over the years, NIDA FOAs in the area of basic HIV, and SUD research have been published to move the field of HIV and SUDs forward. For example,

  • RFA-DA-10-014, HIV/AIDS, Substance Abuse, and Systems Biology (R01) 
  • RFA-DA-16-012, Exploring Epigenomic or Non-Coding RNA Regulation in HIV/AIDS and Substance Abuse (R01) 
  • RFA-DA-16-013, Systems Biology Approaches in HIV/AIDS and Substance Use (R01) 
  • RFA-DA-18-016 Exploiting Genomic or Nucleomic Information to Understand HIV Latency in Individuals with Substance Use Disorders (R61/R33) 
  • RFA-DA-18-008 Exploring Novel RNA Modifications in HIV/AIDS and Substance Abuse (R01/R21) 
  • RFA-DA-19-003 Exploiting Omics Assays to Investigate Molecular Regulation of Persistent HIV in Individuals with Substance Use Disorder (R61/R33) 
  • RFA-DA-21-004 Exploring the Roles of Biomolecular Condensates (BMCs) in HIV replication, latency, or pathogenesis in the context of substance use disorders (R21/R33) 

These RFAs have been quite successful. To date the 31 funded projects from these RFAs generated 166 publications and moved the scientific needle in myriad directions. To select just one topic area for illustration, projects supported by RFA-DA-18-008 further characterized the role of the m6A RNA modification in HIV replication and function and have identified at least two new RNA modifications with roles in HIV replication and function. 

Goal

This initiative will support exploratory studies addressing basic mechanistic questions in HIV infection, replication, latency, and/or pathogenesis (including HAND) in the context of SUDs. Some themes to be encouraged include HIV/ART and SUD interactions with respect to SARS-CoV2, sex differences, sleep, HIV replication in CNS, blood brain barrier, molecular studies, and the intersection between HAND and dementias. This initiative would enable research on biospecimens collected by NIDA-supported HIV cohorts. Junior investigators in new and emerging research areas will be encouraged to apply their talents and technologies to basic research questions in the area of HIV and SUDs.

Potential Research Questions: What are the genes, molecular pathways, cell types, or circuits involved in different aspects of HIV infection, replication, latency, and/or pathogenesis in the context of SUDs? How do they function mechanistically?

Significance: Can these genes, molecular pathways, cell types, and/or circuits shed light on HIV/SUD mechanisms or provide foundational knowledge for future development of potential biomarkers or therapeutic targets?

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


High-throughput Discovery and Validation of Novel Signal Transducers or Small Molecules that Modulate Opioid and other Substance Use Disorder-Relevant Pathways

Posted: September 14, 2020

Background

Many years of research have identified key receptors and signal transduction pathways relevant to addictive substances including nicotinic, opioid, cannabinoid, and dopaminergic pathways. However, there is much we do not know about the modulation of these signal transduction pathways. For example, researchers have used a genetically encoded biosensor to show that opioid receptors respond differently to peptides or non-peptide opioids depending on the subcellular location of the opioid receptor (Neuron 2018). High-throughput small molecule screening of cells expressing similar biosensors might be used to identify compounds with different analgesic efficacy or altered addiction liability. 

Other researchers identified the atypical chemokine receptor ACKR3/CXCR7 as a broad-spectrum scavenger for opioid peptides (Meyrath et al. Nat Comm 2020), making one wonder how many other undiscovered receptors or other signal transduction molecules might interact with opioid or other substance use disorder (SUD)-relevant pathways. 

Similarly, researchers used a nematode genetic screen to identify a conserved orphan receptor GPR139 with “anti-opioid activity.” These found that GPR139 is “co-expressed with MOR in opioid-sensitive brain circuits, binds to MOR, and inhibits signaling to heterotrimeric guanine nucleotide-binding proteins (G proteins). Deletion of GPR139 in mice enhanced opioid-induced inhibition of neuronal firing to modulate morphine-induced analgesia, reward, and withdrawal.” (Science 2019). 

A variety of high-throughput screening approaches have been recently been developed that facilitate the identification of novel targets or small molecules including CRISPR inactivation (CRISPRi) or CRISPR activation (CRISPRa) screens. In these screens, CRISPR is used to turn individual genes off or on in mammalian cells or other simple systems to identify genes with specific phenotypes. For example, CRISPR interference (CRISPRi) has been shown to efficiently silence genes in neurons (Zheng et al., Nat Neuro 2018) and has been used to screen 3200 genes to identify genetic modulators of tau entry into neurons (Rauch et al. Sci Rep 2018) 

Goal

This concept would encourage high-throughput screening or similar transformative approaches to identify receptors, signal transducers, or small molecules that modulate SUD-relevant pathways (opioid, dopamine, cannabinoid, nicotinic, or other appropriately justified pathway). In addition, researchers may perform validation, mechanistic, and/or behavioral studies on a subset of the highest priority hits identified. Some potential high throughput screens that could be exploited include:

  • Cell-based screens using tagged receptors or other reporters to identify novel targets or small molecules that modulate SUD-relevant pathways
  • CRISPRi, CRISPRa, or other functional screens to identify novel SUD-relevant targets in cell culture
  • In silico screens to identify critical signaling hubs or molecules that can be validated by wet lab experiments
  • Barcoding approaches in which libraries of potential genes or other molecules are functionally tested in living animal brains
  • Forward genetic screens in organisms where the mutant genes can be rapidly identified (e.g. C. elegans, Drosophila, and zebrafish)

Significance: Successful studies would likely identify novel modulatory small molecules, receptors, or signal transduction molecules in critical SUD signal transduction pathways. These novel molecules, transducers or pathways could be functionally characterized to determine the mechanistic and behavioral role they play in addictive processes. In addition, these modulatory small molecules, transducers, or pathways could serve as the foundation for the development of new therapeutics for treating SUDs.

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


Tools and Technologies to Explore Brain Biomolecular Condensates (BMCs) Entity: NIH Neuroscience Blueprint Institutes Led by NIDA Staff

Posted: September 14, 2020

Background

Biomolecular condensates (BMCs) are membrane-less subcellular domains that exhibit liquid-like features. BMCs form droplets that coalesce through liquid-liquid phase separation and dynamically exchange molecules with the surrounding environment. Examples of BMCs include the nucleolus, heterochromatin, post-synaptic densities, and plasma membrane signaling clusters. BMCs compartmentalize and concentrate molecules and are now known to have important roles in a variety of processes including regulation of gene expression, organization of subcellular structures, and regulation of receptor kinase signaling at membranes. In the neuroscience realm, BMCs are involved in inhibition of axon regeneration, neurodegeneration, synaptic transmission, and the clustering of calcium channels and neurotransmitter-containing synaptic vesicles.

Gap: Despite the emerging importance of BMCs in neuroscience, the tools we have to monitor and manipulate BMCs in vivo in the nervous system are in their infancy.

Goal

There has been some limited in vivo analysis using optogenetic and chemical methods, much of our current understanding of BMC physics and biology come from in vitro studies. Establishment of new tools that exploit advances in optogenetic, chemogenetic, biophysical, single molecule, or other strategies would 1. enable in vivo BMC monitoring and manipulation and 2. provide much needed insight into BMC nervous system functions. This initiative would also support the development of high-throughput screening technologies to identify candidate molecules and regulators required for BMC formation and maintenance in the CNS. Significance: This initiative will support the development of valuable new tools to monitor or manipulate BMCs in vivo and enable neuroscientists to exploit these tools to answer outstanding questions in basic neuroscience. This research will transform our understanding of the mechanistic role of BMCs in human CNS health and disease and may serve as the foundation for the development of novel BMC-based therapeutics.

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


Mechanistic Studies on the Impact of Social Inequality on the Substance Use Trajectory

Posted: September 14, 2020

Background

A well-established and still growing body of literature points to socioeconomic inequality being a major factor in health outcomes, especially so for mental health and substance use disorder (SUD). This point has been reinforced recently because of two ongoing public crises. First, health disparities have been observed in the impact of COVID-19 – black/African American (AA) and American Indian/Native Alaskan (AI/AN) people are overrepresented among hospitalized patients and death rates are higher among these groups. Further, psychological distress related to COVID-19, resulting from factors such as loneliness, economic anxiety, and uncertainty about the future, is highest among adults with household income of less than $35,000 per year. 

COVID-19 is just one recent public health threat that reveals the social inequality-related health disparities in the US. These health disparities are, in fact, pervasive, particularly impacting racial minority groups. For example, racial minority groups are exposed more frequently to race-related stressors, such as discrimination, shown to impact neural circuitry relevant to SUD. Together, now more than ever, it is evident that a deeper understanding is needed of how socioeconomic inequality impacts various points in the substance use trajectory, especially on the transition from recreational/medical use to SUD and on relapse/recovery.

An important process through which social inequality at the population level works through individuals is by affecting subjective social status or how individuals perceive their social status in relation to others. Subjective social status impacts mental health and substance use in a different, and sometimes more potent manner, than objective markers of socioeconomic status. Importantly, the mechanisms underlying subjective social stress are poorly understood.

Goal

Here, we propose to encourage investigations into neurocognitive mechanisms by which socioeconomic inequality impacts various points in the substance use trajectory. Through mechanistic studies in human and animal models, we expect to arrive at a deeper understanding of the impact of objective and subjective markers of socioeconomic status on the brain and on substance use outcomes. In the long-term, such investigations are expected to inform preventative efforts and therapeutic interventions related to SUD.

Vani Pariyadath, Ph.D., Division of Neuroscience and Behavior


Sleep Disruption and the Impact on Substance Use Trajectory

Posted: September 14, 2020

Background

It is well established that drugs of abuse have a profound impact on sleep as indicated by drug nomenclature, e.g., stimulants reduce sleep, while narcotics (opioids), sedatives (benzodiazepines), and cannabis promote sleep. Apart from simple increases and decreases in sleep duration, drugs also affect sleep architecture such as time spent in different stages of sleep, awakenings, latency to fall asleep, and ability to be aroused and maintain wakefulness.

The interaction between sleep and drug use occurs at all stages, from drug initiation through drug withdrawal, abstinence and relapse. This interaction is not surprising given that many drugs were developed with the intention of altering sleep, and the associated receptors and neurons are both the primary targets of drug action and have critical roles in regulating sleep.

What is surprising is how little is known of the precise mechanisms by which drug abuse and addiction causes specific alterations in sleep patterns, and how these mechanisms contribute to the cycle of abuse / addiction. Even less is known as to the brain mechanisms by which pre-existing sleep dysregulation contributes to the risk for addiction, impairs abstinence and leads to relapse. Furthermore, advances in sleep research have revealed new aspects of sleep whose relation to drug use and addiction has not been established, including contributions from glia, “flushing” of toxins from the extracellular compartments and enhancement of reinforcement learning in artificial neuronal networks by “slow-wave like” oscillatory rhythms.

Goal

This initiative seeks to go beyond the phenomenology of drug / sleep interactions to advance knowledge of the mechanisms that mediate such interactions. Because the goal is to test a priori or novel exploratory mechanistic hypotheses, the initiative will be restricted to pre-clinical research using state of the art experimental brain manipulation and measures. Projects could focus on one or more levels of experimental brain interventions or measures, from molecular to behavioral, and across any phase of the addiction cycle, with a particular emphasis on the interactions related to drug initiation and abstinence/relapse.

Steven Grant, Ph.D. and Rita Valentino, Ph.D., Division of Neuroscience and Behavior


Growing Great Ideas: Research Education Course in Product Development and Entrepreneurship for Life Science Researchers

Posted: September 14, 2020

Background

The prosperity of the Unites States has been largely based on the ability to capitalize economically on ground-breaking discoveries from science and engineering research. While knowledge gained from the NIH-supported basic research frequently advances the fields of science, some results also show immediate potential for broader applicability and impact in the commercial and public health realms. Innovation is properly defined as a realized (commercialized) invention. It is not only about novelty (discovery, invention) but also is about executing, realizing, and fulfilling the said invention or discovery. In the market economies, the realization of research discovery is possible through the commercialization, e.g. bringing the discovery or invention to the markets. Thus, the competence to bring a scientific breakthrough to market is necessary for true biomedical innovation. Unfortunately, an overwhelming majority of the life science workforce does not receive any formal training to empower the biomedical product development and commercialization, or/and entrepreneurship.

Goal

The goal of this program is to develop and deliver a highly specialized curriculum/training course in biomedical innovation and entrepreneurship that prepares NIDA researchers to extend their focus beyond the laboratory and broaden the impact of their basic research projects.

Specific goals include:

  • Create the entrepreneurship program, specially tailored for the many facets of biomedical research, that addresses the challenges inherent in the early stages of the innovation process in life sciences, such as protecting intellectual property and developing regulatory and reimbursement strategies, among others.
  • Provide pioneering, state-of-the-art, evidence-based biomedical product development and entrepreneurship education to undergraduate and predoctoral students, postdoctoral fellows, and/or early-stage investigators who pursue the substance use and addiction research.
  • Cultivate awareness among the academic life scientists about how to gain a clearer understanding of the value of their research inventions in the marketplace, to foster the development of early-stage biomedical technologies and ultimately how to advance their technologies from the research lab into the commercial world.
  • Provide academic researchers who are interested in the formation of a startup company with assistance and offer access to mentorship and opportunities for collaboration.

Elena Koustova, Ph.D., M.B.A., Office of Translational Initiatives and Program Innovations


Managing Comorbid Chronic Pain and OUD

Posted: September 14, 2020

Background

Health care services to effectively treat both non-cancer chronic pain (CP) and opioid use disorder (OUD) are fragmented. Pain clinics and primary care physicians may provide recommended careful assessment and monitoring of patient responses to opioid analgesics and compliance with treatment agreements to assure safe and effective opioid prescribing while managing their pain. However, if a patient exhibits opioid misuse, the patient may be discharged and referred to OUD treatment. OUD treatment programs, while skilled at treating OUD, often lack the expertise and resources to effectively manage pain. To compound a well-intentioned but fragmented system, there is a lack of evidence on medication combinations and/or dosages to address both CP and OUD simultaneously, on non-pharmacological behavioral treatment and complementary interventions that may assist in treating one or both disorders, and on integrated care strategies to efficiently merge these areas of expertise and provide effective interventions in a sustainable and reimbursable manner.

Among this complex population, a significant number of individuals also have Alcohol Use Disorder (AUD) or self-medicate pain with alcohol. For those who use alcohol heavily or have comorbid alcohol use disorder (AUD), pain outcomes are worse and even more difficult to treat without addressing alcohol consumption. Further, the prevalence of General Anxiety Disorder (GAD) and Major Depressive Disorder (MDD) is high among people with co-occurring OUD and CP and these common comorbidities may complicate effective management of comorbid CP and OUD. When the health care system does not adequately address CP and OUD, and attendant psychiatric comorbidities, patients may attempt suicide and/or self-medicate with street drugs, alcohol, and/or anxiety medications, which all increases the risk of overdose.

Goal

As part of the National Institutes of Health’s (NIH) Helping to End Addiction Long-term (HEAL)SM Initiative, NIH intends to establish a national network of researchers to facilitate multidisciplinary team science collaborations that can create actionable, translatable, and sustainable treatments to improve the capacity of the health care system to effectively respond to the opioid epidemic. This network will consist of:

1. Centers on Co-managing CP and OUD (C3POs): These programs will conduct clinical research and adaptive clinical trials, including pragmatic clinical effectiveness, implementation and hybrid implementation-effectiveness studies.

2. Research on Related DSM-5 Diagnoses (R2D2) Coordination and Dissemination Center: This center will manage logistics, harmonize common data elements, disseminate findings and products generated from the C3PO network, coordinate across the network, and identify areas of synergy and opportunities both within and external to the broader NIH HEAL Initiative.

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


Advancing Exceptional Research on HIV/AIDS and Substance Use

Posted: September 14, 2020

Background

This initiative aims to support highly innovative applications on HIV/AIDS and substance use research. It complements the NIDA Avant-Garde and Avenir Award programs for research at the intersection of HIV/AIDS and Substance Use Disorders (SUD).

Despite the many scientific advances, HIV continues to be a major health problem across the globe. Current therapies and prevention strategies are not reaching key populations that are at high risk for HIV including People who use drugs (PWUD). Research at the intersection of substance use, SUDs, and HIV/AIDs must consider new realities in the domestic and international drug epidemics, shifting policies about the legalization of substances like marijuana, new tools to address HIV and SUDs including long-acting treatments and Pre-Exposure Prophylaxis (PrEP), the availability of big data, and the evolution of tools and platforms to support innovative bio-medical research. Also of interest is a successful cure strategy that eliminates hidden HIV reservoirs, including those persisting in the central nervous system. Therefore, this initiative is designed to support innovative research projects that have the potential to open new areas of HIV/AIDS research and/or lead to new avenues for prevention and treatment of HIV/AIDS among substance users. The ‘Advancing Exceptional Research on HIV/AIDS and Substance Use’ concept is open to both individual researchers and research teams and is not limited to any one area of research.

Goal

This concept focuses on innovative research projects that have the potential to open new areas of HIV/AIDS research and/or lead to new avenues for prevention and treatment of HIV/AIDS among people with substance use disorders. The nexus with SUD should be clearly described. This concept is not limited to any one area of research on HIV and substance use. Applications submitted in response to this initiative must address one or more of the NIH HIV/AIDS Research Priorities: https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-137.html.

Redonna Chandler, Ph.D., AIDS Research Program


HIV/AIDS High Priority Substance Use Research

Posted: September 14, 2020

Background

The National Institutes of Health (NIH) reconfigured the HIV research priorities in 2015 as specified in the NOT-OD-15-137: NIH HIV/AIDS Research Priorities and Guidelines for Determining AIDS Funding. The ‘HIV/AIDS High Priority Drug Abuse Research’ initiative was introduced immediately following the release of these new NIH HIV priorities to stimulate research in those high priority areas. This initiative aims to continue addressing the high priority HIV research areas in the context of substance use disorder (SUD).

Goal

The purpose of this initiative is to stimulate high priority research relevant to substance use disorder and HIV/AIDS. NIH high priority research areas of relevance include engaging people who use drugs (PWUD) who are at high risk for HIV into screening and preventive services, linking and retaining PWUD living with HIV into HIV and OUD care cascades to achieve durable viral suppression, and addressing HIV comorbidities e.g. HCV, HIV-associated neurocognitive disorder (NCD), to improve health outcomes. Also of interest are basic and clinical research studies that lead to novel therapies, cure strategies, and vaccines to treat and prevent HIV and SUDs in high-risk marginalized populations.

Vasundhara Varthakavi, D.V.M., Ph.D., AIDS Research Program (ARP)


Coordinating Center for the HIV/AIDS and Substance Use Cohorts Program

Posted: September 14, 2020

Background

The National Institute on Drug Abuse (NIDA) supports a program of longitudinal cohorts to address emerging and high priority research on HIV/AIDS in the context of injection and non-injection substance abuse. These cohorts provide a strong resource platform for current and future collaborative efforts with other investigators to address emerging questions related to HIV pathogenesis, prevention, and treatment in the context of substance abuse, as well as to foster the creativity and efficiency of investigator–initiated research projects. The diverse research activities among these cohorts include basic immunologic, and virologic studies, as well as studies on HIV prevention and treatment, and the co-morbidities and co-infections associated with HIV and substance abuse. NIDA has determined that a coordinating center (CC) is needed in order to take advantage of these rich sources of data and bio-specimens and optimize collaborations among both the cohort investigators and other researchers not funded under the cohort program. In addition, the CC is expected to establish a virtual repository, and facilitate the leadership of the cohorts steering committee (SC), consisting of representatives from the NIDA-funded cohorts and NIDA staff.

Goal

The purpose of this concept is to support a single Coordinating Center (CC), which will provide scientific leadership, overall management and primary oversight of the research activities funded through the NIDA HIV/DA cohort studies. Importantly, the CC is required to: 1) ensure reliability and consistency of data collected across the cohorts, 2) support development, tracking, and reporting of performance metrics, 3) establish a virtual repository, and 4) facilitate the leadership of the cohorts steering committee (SC) consisting of representatives from the NIDA-funded cohorts and NIDA staff.

Raul Mandler, M.D., Division of Therapeutics and Medical Consequences


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 


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 


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 


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 


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 


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