National Advisory Council on Drug Abuse (NACDA) Approved Concepts

A concept describes the purpose, scope, and objectives of a potential funding opportunity. Concepts are posted to give interested researchers additional time to plan for application submissions. Approved concepts are usually developed into Requests For Applications (RFAs), Program Announcements that include set-aside funds (PASs), or Program Announcements with special receipt, referral and/or review considerations (PARs). The NACDA conducts most, but not all, NIDA concept clearances. Concepts may also be cleared through other public venues.

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:


Behavioral & Integrative Treatment Development Program

Posted May 2022

Background

Behavioral treatments play a critical role in most evidence-based substance abuse interventions, and often constitute the entire treatment. This FOA will support Stages I, II and III behavioral and integrative intervention research with the goal to advance science, including treatments and interventions that are intended to be more efficient, better tailored to individuals, or more readily transported to the community. These stages focus on intervention development and efficacy testing.

Over the past two decades, numerous evidence-based behavioral and integrative treatments for addiction have been created. With advances in neuroscience, pharmacology and device-development, it is evident that to improve clinical outcomes, more needs to be done to incorporate new scientific discoveries into behavioral treatment and intervention development. In addition, as more information is elucidated about how treatments work and for whom, and new technologies become available, more can be done to make treatments more easily transportable to community settings. The Behavioral and Integrative Treatment Development Program seeks to achieve these goals.

Goal

The overarching goal of this funding opportunity announcement (FOA) is to produce maximally efficacious behavioral interventions to treat substance use and dependence. It is also intended to support research to promote medication/treatment adherence, prevent HIV and take advantage of new knowledge in neuroscience, and take advantage of new technologies and pharmacotherapies that may improve tangible outcomes of behavioral interventions (e.g., improving cognitive function). This FOA underscores the importance of fostering research aimed at boosting intervention effects to produce targeted treatments for different types of substance use populations (including pregnant women, populations with comorbid psychiatric disorders, and prisoners) or populations with pain. Stages of treatment development will include Stage I, Stage II and Stage III efficacy studies (randomized clinical trials, adaptive designs, SMART designs, experimental therapeutics approach) of behavioral, combined, or integrated treatment interventions, adherence interventions, and prevention interventions for HIV risk behaviors. This includes treatment dose-response studies, and studies of the optimal sequencing of treatment, adherence, and HIV prevention interventions. Research on the treatment of substance use disorders, including illicit drugs, prescription medications, nicotine (including e-cigarette cessation), alcohol and multiple drugs. Of particular interest are studies that seek to determine basic mechanisms of behavior change, within the context of behavioral treatment research.

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


Mechanisms and Targets at the Intersection of HIV and Addictive Drugs

Posted May 2022

Background

HIV infection leads to a plethora of changes in the function of host proteins in the brain through changes in their expression or post-translational modifications. These effects of HIV on host proteins can affect viral replication, latency, and neuroinflammation. They can also affect neural or glial functions that are integral to normal sensory, affective and cognitive processes. In this context, significant gaps exist in our knowledge of the precise mechanisms by which HIV viral proteins interact with specific biological targets in the host cells and the role of these interactions in the development of the CNS complications in people living with HIV. While there is evidence that certain viral proteins and addictive substances share common targets that lead to increased vulnerability to cognitive disorders, significant gaps exist in our knowledge regarding the mechanisms that contribute to the development of neuropathogenesis and cognitive impairments by HIV infection, addictive substances, and antiretroviral therapies.

Goal

The goal of this initiative is to support research focusing on elucidating the mechanisms and targets through which addictive drugs and HIV infection converge to induce changes in brain function. This initiative is also intended to encourage the application of emerging technologies in molecular biology and computational methods toward identification of targets and tools for probing the mechanisms that contribute to the complex interplay between HIV infection and substance use disorders and for potential development of therapeutic approaches to prevent or mitigate the deleterious effects of HIV infection and addiction.

Sam Ananthan, Ph.D., Division of Neuroscience and Behavior


Novel Tools and Pipelines For High-Resolution Spatial Characterization of HIV Infection, Persistence and Pathology in CNS Tissues, in the Context of Substance Use

Posted May 2022

Background

Understanding how different cell types contribute to the progression of the neuropathology underlying HIV-Associated Neurocognitive Disorder (HAND), and how these mechanisms are affected by substance use, requires methods to track the spatial distribution of HIV infection and neuropathology in space and time, at high resolution in brain tissue with preserved 3D structure and connectivity. Although PET and MRI-based imaging approaches such as DTI and resting state fMRI have revealed consistent structural and connectomic abnormalities associated with HAND and HIV infection, the resolution of these non-invasive imaging approaches is still too limited to provide detailed information about their cellular underpinnings. In contrast, single-cell genomics initiatives such as SCORCH are generating critical high-resolution information about cell-types affected by HIV, but information related to tissue structure is usually lost in these studies, due to the cell dissociation required to apply these sequencing methods.

Innovations in several areas supported by the BRAIN initiative, including advanced optical technologies for ex-vivo ultrastructural and molecular imaging (e.g., expansion microscopy, multibeam scanning EM ) tissue preparation (e.g., embedding and clearing methods ) spatial omics (e.g., MERFISH, SLIDEseq), viral barcoding (RABID-seq; BRICseq) and novel immunoreagents amenable to multiplexed proteomic imaging (e.g., nanobodies) offer unique opportunities to transform the understanding of how CNS cell identity and morphology/connectivity contribute to HIV infection, compartmentalization and pathology. All these technologies are applicable to tissues originating from animal models (rodents and non-human primates) but some are also applicable to human tissues, either originating from postmortem tissue biobanks, or freshly collected upon surgical resection.

Goal

The goal of this initiative is to stimulate the development, validation, and application of novel ex-vivo molecular imaging toolsets, along with necessary tissue procurement, tissue processing and data pipelines, to enable high-resolution spatial analysis of HIV infection, persistence, and neuropathology, in the context of brain cellular diversity, ultrastructure, and connectivity. Proposals will be expected to apply these pipelines to biological test cases investigating the mechanisms of HIV-associated neuropathology in the context of substance use. Leveraging these technologies will provide essential information to contextualize and integrate prior knowledge from brain imaging and genomics studies.

Olivier Berton, Ph.D., Division of Neuroscience and Behavior


Career Development Awards in Addiction Implementation Science

Posted May 2022

Background

Realizing the return on public investment in the development of evidence-based treatments and preventive interventions to address the ongoing overdose crisis depends on a cadre of skilled researchers to help move these interventions into routine clinical practice. Implementation science is a relatively new discipline that focuses on identifying modifiable barriers to the uptake and sustained use of evidence-based practices in real world clinical settings. While this field has grown rapidly over the past 15 years, including in addiction, there are a limited number of seasoned researchers with dual expertise in addiction research and implementation science, limiting the field’s capacity to respond to continued calls for implementation-focused research in this area. There is a pressing need for a deeper bench of researchers who can be called upon to meet these ongoing challenges.

Goal

This concept would support early career researchers or clinician-researchers with foundational backgrounds in addiction to develop expertise in implementation science. Projects would support training in implementation science methods, and a research project that would apply these to at least one of the four priority domains of the HHS Overdose Prevention Strategy: primary prevention, OUD treatment, harm reduction, or recovery support services. The overarching goal is to build a cadre of implementation researchers who can contribute to addressing the current overdose crisis, develop research careers that will impact the quality of clinical practice generally, and become the next generation of implementation experts and mentors.

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


Heal Initiative: Research to Foster an Opioid Use Disorder Treatment System Patients Can Count On

Posted May 2022

Background

Individuals with opioid use disorder (OUD), families, and payers report needing credible information to help them select effective providers. At the same time, evidence-based practices, such as medications for opioid use disorder (MOUDs), are not routinely provided to patients or taken for what is considered sufficient duration, nor are efficacious, innovative approaches such as injectables speedily adopted. Done carefully, the collection and reporting of quality measures could address these and other issues in the current system. Quality measures can assess structural characteristics of providers, such as the qualifications of its staff or the availability of evidence-based interventions, clinical processes such as the percent of patients receiving a specific evidence-based intervention, or patient outcomes such as reductions in drug use. Though widely used in health care, and increasingly developed and applied to opioid use disorder (OUD) treatment, knowledge gaps related to the development, implementation, and effects of quality measurement and management warrant rigorous research to develop systems that can identify of effective opioid use disorder treatment providers, promote improvement, and to support the timely, efficient dissemination of new treatments.

Goal

To support rigorous research building on existing quality measurement and management efforts to substantially fill gaps required for the development of feasible, effective quality measurement and management systems that can help patients, families, and payers identify effective providers and promote improvements in patient outcomes.

Sarah Q. Duffy, Ph.D., Division of Epidemiology, Services and Prevention Research


HEAL: Rapidly Assessing the Public Health Impact of Emerging Opioid Threats

Posted May 2022

Background

There is an urgent need to rapidly assess the incidence and impact of emerging illicit drugs and the health consequences of their use. Illicit chemists now market potent drugs of abuse ripped from scientific and patent literature. This profound source of structures has resulted in a rapidly evolving major Public Health problem, ie, the fentanyl/fentalog (fentanyl-related opioids) crisis. As fentalogs have flooded the illicit opioid market, overdose mortalities skyrocketed. Their detection was initially problematic and even today urine test strip kits are highly variable in their ability to detect different compounds. The limitations of these detection tools have forced clinicians to consider fentalogs as a homogenous group. It is worth noting therefore, that in the early days of the fentalog crisis, anecdotes suggested fentanyl was very long-lasting and poorly antagonizable. These reports diminished as the ultrapotent and long-lasting carfentanil disappeared from the drug supply, perhaps an example of the perils of generalization. The field still struggles to understand and mitigate the impact fentalogs have wrought. However, illicit manufacturers have moved on, now selling ultrapotent "nitazene" opioids (compounds ripped out of 1960’s literature). We don’t know nitazene’s prevalence because clinicians and medical examiners lack assays to identify and quantify them in patient body fluids, metabolism information is not available and urine test strips have not been developed. Certainly, users cannot know whether nitazenes are contained in the illicit tablets they bought. Detection and quantification are pre-requisites to understand any threat and are essential to developing evidence-based methods to reduce and treat the harms they cause. This is especially true in today’s rapidly evolving illicit drug market. It is not a safe assumption that the drugs encountered yesterday are essentially the same as today, that must be demonstrated using methods that are either not yet in existence or not yet practical.

Goal

To support research that will rapidly and efficiently evaluate the public health impact of new illicit drugs used by individuals. The evaluations may include analytical methods development, assessment of pharmacokinetic properties and abuse liability, and development of methods to limit their use and treat individuals who are using these new uncharacterized drugs. In addition, while this concept addresses current needs, it also builds-in funds to allow awardees to rapidly bring their discoveries and expertise to bear on the future generations of threats that are surely coming.

Aidan Hampson Ph.D., Division of Therapeutics and Medical Consequences


HEAL Initiative: Opioid Use Disorder Care Pathways for Individuals with Histories of Exposure to Violence

Posted May 2022

Background

Prior research demonstrates a substantial association between exposure to violence and opioid use. The majority of people diagnosed with substance use disorders have been exposed to violence; and among those with injection drug use, over a quarter have experienced a new episode of violence in the past month. Victimization can be linked to opioid use through a variety of pathways. Victimization can result in physical pain and mental distress leading to substance use initiation and escalation. Victimization can also occur as a consequence of drug seeking behavior. Social and structural determinants of health, such as housing insecurity and justice-system involvement, also increase individual risk for opioid use and exposure to violence.

Despite the strength of the association between exposure to violence and OUD, research about the extent to which and the ways in which victimization history affects OUD treatment, retention in treatment, and recovery is limited. Victimization experiences may result in PTSD, characterized by intrusive memories, avoidance behaviors, negative cognitions and mood, and changes in physical and emotional reactions. Over a third of people diagnosed with OUD are estimated to have symptomatology consistent with PTSD. Although a PTSD diagnosis does not seem to predict poorer treatment retention on medications for opioid use disorder (MOUDs), concurrent treatment of PTSD and OUD has been shown to dramatically improve retention on MOUDs. Likewise, research with patients in OUD treatment has shown that exposure to traumatic events and a worsening of PTSD symptoms during the course of OUD treatment are associated with increased risk of treatment interruption.

Goal

This concept highlights the Helping to End Addiction Long-Term (HEAL) initiative’s interest in providing evidence-based services to address opioid use and traumatic stress to individuals who have histories of exposure to violence. This concept is to encourage intervention research focused on one of two care pathways. The first is identifying and addressing opioid use prevention and treatment needs for individuals who are seeking services in settings that address the needs of crime victims, including but not limited to domestic violence shelters, child advocacy centers, sexual assault response providers, human trafficking organizations, child welfare, and victim advocacy organizations. The second care pathway is aimed at individuals who are seeking treatment for opioid use disorders (OUD). This pathway focuses on screening for exposure to violence, and if indicated, identifying and treating post-traumatic stress disorder (PTSD) among individuals who have already been diagnosed with an OUD. Specifically, this initiative would support awards to test care pathways that either: 1) provide OUD screening, prevention and treatment referral or services to victims of violence in victim service settings; or 2) provide PTSD screening and treatment for individuals in OUD treatment. Studies must include OUD relevant outcomes, but may propose interventions to treat or prevent stimulant use disorder in combination with OUD.

Carrie Mulford, Ph.D., Division of Epidemiology, Services, and Prevention Research


CODE (Cause of Death Elucidated) in Drug Overdose: Rapid and Portable Cause of Death Detection Technologies to Improve Drug Overdose-Related Mortality Counts

Posted May 2022

Background

Over the past 20 years, drug-involved overdose deaths have increased sharply, and this has strained the resources needed to accurately track the drug epidemic. About 20% of drug overdose deaths do not indicate the drug involved. Because drug overdose mortality counts describing specific drugs are regularly underreported, this severely hinders accurate monitoring of death rates and curbs the ability of those in public health, research, policy, and government to identify threats in a timely manner and to implement effective interventions or care in communities impacted by drug overdoses.

Currently, drug-involved overdose deaths represent 1 in 6 death investigations, and both coroner and medical examiner offices are facing overwhelming caseloads that require comprehensive toxicology analysis. A significant hurdle to specifying the drugs involved in overdose deaths is the lag time in obtaining results from comprehensive toxicology testing. During the drug epidemic, the backlog in toxicology testing has increased to be months-long. This backlog is worsened by a chronic shortage of trained forensic staff, and the emergence of new synthetic drug analogs. Therefore, there is a critical and immediate need to improve and accelerate toxicology testing in drug overdose death cases.

Goal

The goal is to support research and development of new detection devices and component technologies that reduce the time and the cost to identify drugs involved in suspected overdose deaths. Some key features of the detection devices and technologies include but are not limited to: accuracy, response time, affordability, portability and accessibility. These devices and component technologies should be developed as a practical tool for coroner and medical examiner offices.

Proposals may include but are not limited to: 1) designing and engineering new component technologies and devices, 2) developing prototypes, 3) benchmarking prototypes to characterize performance, 4) software development for instrumentation, data analysis and reporting, and 5) system improvements based on feedback and testing.

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


Opioid Misuse Prevention Effectiveness Research Among Youth and Families Involved With the Child Welfare System

Posted May 2022

Background

In FY 2019, approximately 3.5 million children received a child protective services investigation, 672,600 children were served by the foster care system, and 424,000 children resided in foster care. Parental drug abuse was the second leading circumstance associated with a child’s removal from the home in 2019 (following neglect). Nationally, the increases in overdose deaths, largely driven by opioids, has been associated with increased reports of maltreatment and foster care entries. In addition, rates of substance use among youth involved in the child welfare system are high, and youth substance use is a strong and reliable predictor of opioid misuse in early adulthood. Implementing prevention services among child-welfare involved youth and families has the potential to substantially reduce immediate and multigenerational risk for opioid and other substance misuse and use disorders. Although interventions exist to reduce risk for substance use, opioid misuse has not been a primary outcome measure and few interventions have been evaluated for effectiveness among child-welfare involved populations. It is unknown how well the benefits from existing interventions, which are typically delivered in schools or to families living together, will generalize to those who experience instability in caregiver relationships, transitional living arrangements, and multi-level risk for substance use.

Goal

This initiative proposes to fund research to test strategies to prevent opioid and other substance misuse and use disorder among youth and families involved with the child welfare system. Involvement with the child welfare system will be defined broadly, including youth or families: a) identified as candidates for entry into the foster care system by the state’s FFPSA Title IV-E Prevention Plan, b) investigated by child protective services, c) receiving services from the child welfare system, or c) youth aging out or families exiting from the child welfare system. The types of studies investigators might propose include but are not limited to interventions to prevent opioid misuse among youth receiving services by the child welfare system, intergenerational interventions that combine treatment of parental substance use with preventive strategies at the child level, or interventions to mitigate risk for opioid misuse and adverse outcomes among young adults aging out of foster care.

Barbara Oudekerk, Ph.D., Division of Epidemiology, Services, and Prevention Research


Development and Validation of Virtual Assessments to Study Children and Caregivers in Their Natural Environment

Posted May 2022

Background

Prompted by the COVID-19 pandemic, an unprecedented opportunity exists to leverage technological advancement, acceptance, and ubiquity to extend the developmental clinical research environment further out of laboratory settings and into the community and individual environment. Importantly, remote technology, the frequency (up to continuous, real-time) of data collection, and the integration of the home environment affords developmental researchers the opportunity to study multilevel influences on developmental trajectories. The impacts of such approaches can allow for greater ecological validity in understanding the role of daily experience and social interaction on development, as well as expand the scope of research into populations typically underrepresented in developmental cognitive research.

This concept is intended to serve as a vehicle to

  1. Transform the makeup of developmental populations by expanding its representativeness and lowering the burden of families to participate in clinical neuroscience research studies.
  2. Leverage existing technologies (e.g., phones, video conferencing, biosensors) to get densely sampled, ecologically valid data within a child’s natural and built environment.
  3. Develop innovative new technologies and paradigms to expand the scope of developmental research in at-home settings.

Goal

This concept seeks applications that will establish validated virtual measures of sociocultural, biobehavioral and environmental factors that underlie developmental mechanisms and trajectories of substance use exposures. Appropriate research objectives are:

  • To establish and validate environmental, behavioral, clinical, and psychophysiological assessments to study children and their caregivers in their natural environments.
  • To establish construct validity of remote assessments by comparisons to the standard in-person assessments they replace.
  • To establish innovative analytic tools and methods that integrate multidimensional, dense data collected remotely and longitudinally.
  • To identify challenges to participant recruitment and retention and develop methods, including effective community engagement and participatory research methods, to minimize participant burden and widen representation.

Janani Prabhakar, Ph.D. and John Fedota, Ph.D., Division of Neuroscience and Behavior


Therapeutics Development for Opioid Use Disorder in Patients with comorbid Commonly Occurring Mental Disorders

Posted May 2022

Background

Opioid Use Disorder (OUD) and commonly occurring mental disorders (COMD) frequently co-occur in the general population. There are common risk factors for both conditions, including genetics and epigenetics, environmental influences such as stress, trauma, adverse childhood experiences, etc. A co-occurring mental disorder can often lead to or exacerbate the OUD and vice versa. The co-occurrence of a mental disorder and OUD, worsens clinical outcomes for both, leading to increased overdose and death.

There are therapeutic interventions that are safe and effective for OUD or COMD, which may be effective to treat OUD in patients with comorbid COMD. Moreover, there are pharmacological targets that may be common to both clinical conditions, and, similarly, there are medications that may be effective for both too.

The current confluence of the Opioid Crisis and the COVID-19 pandemic increases the urgency of the public health need to develop treatments that target OUD in individuals with co-occurring COMD. Thus, the COMD population that is often excluded from OUD clinical trials will be the focus of this treatment development.

The purpose of this FOA is to support research that accelerates the discovery and development of safe and effective therapeutics for OUD in patients with co-occurring COMD. The therapeutic interventions may include medications, devices, or digital therapeutics.

Goal

The goal is to support research that addresses the urgent need to have safe and effective therapeutics for OUD in patients with co-occurring COMD.

Tanya Ramey, M.D. Ph.D. and Matthew Seager, Ph.D., Division of Therapeutics and Medical Consequences


Research to Develop and Implement Interventions to Prevent Opioid Misuse in Community Health Centers

Posted May 2022

Background

An estimated 9.5 million people misused opioids in 2020, of which 9.3 million misused prescription pain relievers. There is need to develop, test, and implement preventive strategies that can decrease the incidence and prevalence of opioid misuse, OUD, and overdose deaths, particularly in populations that are at risk for substance misuse and other negative health and social outcomes due to systemic, environmental, structural, economic, and other factors. Community Health Centers (CHCs) are safety net clinics that provide primary and preventive health care and health education, focused on overcoming barriers and enabling access to affordable health care among traditionally underserved populations. CHCs are well positioned to serve as a formal point of entry into evidence-based opioid misuse prevention services because they reach large numbers of persons impacted by the opioid crisis and are located across the nation in low-resourced areas. CHC patients are more likely to experience social conditions that are risk factors for substance misuse, suggesting that engaging in prevention interventions may be beneficial for this population. Due to their payment system and integration with the communities they serve, CHCs offer unique opportunities to sustainably support prevention interventions.

Goal

As part of NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to the national opioid public health crisis, NIDA previously launched the HEAL Prevention Initiative, supporting research to improve our ability to prevent opioid misuse among individuals who experience risk. As part of the HEAL Prevention Initiative, this FOA will develop or adapt interventions to prevent opioid misuse among patients served by community health centers (CHCs). The goal is to support research that will, ultimately, improve the ability of CHCs to provide screening and prevention services to patients who may experience risk for opioid misuse. Projects supported through this initiative may include 1. intervention research to develop or adapt intervention strategies to prevent opioid misuse and OUD for delivery within CHCs or 2. services research to study implementation frameworks for delivering efficacious prevention interventions within CHCs.

Sarah Steverman, Ph.D., Division of Epidemiology, Services, and Prevention Research


Multilevel Interventions to Reduce Harm and Improve Quality of Life for Patients on Long Term Opioid Therapy

Posted May 2022

Background 

Approximately 13 million Americans met criteria for long term opioid therapy (LTOT), defined as the use for 90 days or longer. One iatrogenic consequence of LTOT is the presence of physiological problems that ranges from physical dependence to OUD. While both physical dependence (acute tolerance & withdrawal) and OUD (compulsive use despite harmful consequences) have accepted clinical diagnosis and symptoms, there is a large population of LTOT patients who fall in between these conditions that are clinically ambiguous and poorly defined. For example, some have diagnosed these patients with Complex Persistent Dependence, Complex Persistent Opioid Dependence (CPOD) or protracted abstinence syndrome. Clinical diagnosis none withstanding, chronic and/or high dose exposure can induce poor pain control, functional decline, psychiatric instability, and behaviors related to harmful opioid use. For example, long-term opioid use may result in failure to fulfill major role obligations at work/school/home, reduced engagement in important social, occupational or recreational activities, or a rise in physically hazardous situations. While these behaviors are included in the DSM for defining OUD, if the patient does not exhibit compulsive drug use behaviors, these individuals are often excluded from OUD care and bounced back to a pain specialist or a PCP who may not have sufficient training in managing these opioid risks. Another unfortunate consequence of LTOT is that many providers may be unwilling to accept new chronic opioid patients.

Importantly, the nationwide effort to taper opioids following federal guideline recommendations added to this cohort of patients. A portion of LTOT patients underwent aggressive forced tapering beyond guideline recommendations and tapering can also induce/exacerbate these adverse symptoms. As a consequence, these patients exhibit elevated risk for an overdose event, suicide ideation among other mental health crises, and damaged patient-providers relationships that adversely impacted patient health. Because these patients do not meet DSM criteria for OUD, clinical care for this population can be confusing for providers and equally frustrating for patients. Moving forward, efforts are needed to strengthen the evidence for best tapering practices that are tailored, flexible, and patient-centered.

Goal

Adequate care for patients on LTOT requires effective interactions between patients and clinicians and between clinicians and health system leadership, in the context of supportive health system policies; a lack of attention to these complex and dynamic interactions has contributed to the current pain crisis and opioid epidemic. This concept will evaluate multi-level solutions for patients on long-term opioid treatment who are exhibiting harmful opioid behaviors, but do not meet criteria for OUD. Interventions can target patients, health care providers (inclusive of pharmacists) or health care systems to reduce chronic pain and opioid-related risks and improve quality of life. Patients with lived experience should consult on these projects. A resource center is also needed to identify methods for defining and characterizing this complex patient population, including specification of clinical symptoms and development and assessment tools that will be psychometrically validated. In addition, this Resource Center will create risk-benefit decision tool to assist health care providers when opioids should be continued as prescribed, tapered, or tapered and discontinued.

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


Ending the HIV Epidemic: Focus on Justice Populations with SUD

Posted May 2022

Background

The US cannot end the HIV epidemic without attending to the risks and service needs of justice-involved populations who use drugs. Initiatives aimed at ending the HIV epidemic in the US have largely ignored justice settings, which serve populations at substantially elevated risk for HIV. Injection drug use, one of the key risk factors for HIV transmission, is common among justice involved individuals. Thus, addressing the confluence of HIV and injection drug use among justice involved individuals is critical to ending the HIV epidemic. NIDA has a long and productive history of conducting addiction services research in justice settings. A robust toolkit of clinical interventions to prevent and treat HIV exists, but implementation science is needed to address significant service delivery gaps at all points of the HIV care cascade.

Goal

This goal of this initiative is to focus on HIV prevention and treatment implementation research in justice populations with substance use disorders. The proposed initiative would focus on creating national research capacity targeted to geographic regions where there are spikes in HIV cases. Through this initiative, studies would be conducted that systematically identify individuals at most risk for acquiring or transmitting HIV as they come into contact with the justice system and connecting this population with relevant HIV and substance use prevention and treatment services.

Tisha Wiley, Ph.D., Division of Epidemiology, Services, and Prevention Research


HEAL: Translating Research to Practice to End the Overdose Crisis

Posted May 2022

Background

In 2020, the United States hit a record of more than 100,000 overdose deaths. Research funded through the National Institutes of Health offers numerous promising approaches to responding to this entrenched public health crisis. However, research does not always readily translate to practice and new approaches are needed to accelerate the translation of promising research findings to practice. Methods such as implementation science, hybrid implementation/effectiveness trials, and dissemination research are critical tools for achieving this acceleration.

Goal

This goal of this initiative is to provide support for an array of research approaches that address opioid use and the intersection of pain and opioid use, with the goal of accelerating the translation of research to practice in these domains. This initiative emphasizes the need to address understudied areas of opportunity, particularly those that may be fundamental barriers or facilitators to reducing overdose deaths at the individual, provider, organizational, community, or system levels.

Tisha Wiley, Ph.D., Division of Epidemiology, Services, and Prevention Research


Workforce Interventions to Improve Addiction Care Quality and Patient Outcome

Posted May 2022

Background

Recruiting, training, and retaining a robust and highly qualified behavioral health workforce is essential to delivering effective services that address opioid misuse and addiction. However, high rates of turnover among addiction services staff and increases in demand for care have substantially impacted access to, cost of, and quality of services, and undermine efforts to implement innovative approaches to care. In 2018, the Health Resources and Services Administration (HRSA) projected that demand for addiction counselors will exceed supply by approximately 38% in 2030; this trend has likely only worsened in response to the COVID-19 pandemic. Even so, little research has been conducted to identify ways to address these challenges in recruitment, training, and retention for the addiction services workforce.

Goal

The goal of this initiative is to design and test interventions that address the modifiable dynamics that influence workforce recruitment, training, and retention, with the ultimate goal of improving quality of care and patient outcomes. Dynamics of interest include those at the individual, organizational, and system levels, e.g., burnout, vicarious and secondary trauma, clinical supervision, influence of regulatory infrastructure, retention efforts by employers, training infrastructure, etc. Multidisciplinary teams with diverse backgrounds (e.g., organizational behavior experts, health services researchers, clinicians, etc.) are essential to the goals of this initiative.

Tisha Wiley, Ph.D., Division of Epidemiology, Services, and Prevention Research


Addressing Racial Equity in Substance Use and Addiction Outcomes Through Community-Engaged Research

Posted February 2022

Background

Despite past research efforts, racial and ethnic related health disparities remain in rates and outcomes of substance misuse, addiction, and related factors. Experiences of racism, racially related structural barriers, and social and political determinants of health are strongly implicated in these disparities. Community Engaged research is an approach that has demonstrated significant promise for meaningful and actionable research, supporting the discovery of solutions to address entrenched health disparities.

Goal

The goal of this FOA is to support research that will have a major impact in identifying, developing, implementing, or testing strategies to prevent, reduce, or eliminate racial or ethnic disparities in substance use and addiction, thereby advancing health equity. Research should move beyond simple conceptions of race and ethnicity, conceptualizing race as a social construct and meaningfully unpacking race and ethnicity, including by integrating experiences related to structural inequities and social determinants of health. Community engaged research has features that will ensure more rapid advances in this scientific area. As such, this FOA will support collaborative community partnered investigative teams to conduct research projects that address issues prioritized by the community and that reflect lived experience.

Kathy Etz, Ph.D., Director, Native American Program, Division of Epidemiology, Services, and Prevention Research


Avenir Award for Research on Racial Equity

Posted February 2022

Background

The addiction field is in need of scholars who can bring a deep understanding of the social construction of race and its manifestations in the daily lives of U.S. residents to inform directions for system-level changes to policy and practice.  Racial/ethnic disparities in substance use-related outcomes have been documented, often affecting Native American, African American, and Latinx individuals, among others.  What is less well-understood is how various resources that are not equitably distributed (e.g., personal and familial resources, social connections, opportunities for advancement, opportunities for forgiveness, accessibility of support services, etc.) interact with race/ethnicity to create poorer outcomes related to substance use, progression to SUD, treatment for SUD, and recovery.  Research on drug use, misuse, and addiction must move beyond the important work of measuring disparities to the task of answering challenging questions that will improve outcomes.

Goal

This initiative invites applications for awards to support exceptionally creative, early career investigators with the expertise and skills to make significant contributions to the study of equity for racial/ethnic minority groups that experience poorer outcomes related to substance use and substance use disorders.  Proposed projects should lead to advances in equity across populations affected by substance use related harms.  This concept seeks cutting-edge research that will inform strategies for 1) addressing bias and discrimination in measurable, impactful ways, 2) building trust within diverse communities despite historical and persistent injustices, and 3) advancing a culture of equity within organizations and institutions charged with serving the needs of diverse individuals.

Aria Crump, Sc.D., Deputy Branch Chief, Prevention Research Branch, Division of Epidemiology, Services, and Prevention Research


Neurocognitive Mechanisms Underlying the Impact of Structural Racism on the Substance Use Trajectory

Posted February 2022

Background

In July 2020, NIDA established the Racial Equity Initiative (NIDA REI) to organize the Institute’s efforts to eliminate racism in NIDA’s workplace, scientific workforce, and research portfolio. This concept is a part of the NIDA REI’s commitment to support research that addresses the extreme disparities in substance use for minoritized groups. 

In the last decade, some progress has been made towards unpacking the neurocognitive mechanisms underlying the impact of various psychosocial factors on the substance use trajectory, but the effects of structural racism specifically remain a major gap in our knowledge. Epidemiological studies have pointed to discrimination increasing the risk for substance use initiation, SUD diagnosis, and SUD severity, and to the impact of multiple social determinants of health, such as adverse childhood experiences, on the substance use trajectory. However, these vulnerability pathways have generally not been investigated in laboratory settings contextualized in a structural racism framework.

These gaps in basic science stem in part from 1) insufficient collaboration between neurocognitive researchers and those with field and community expertise, and 2) a dearth of available experimental methods to adequately model the effects of racism.

Goal

This concept seeks to address the gap described above by supporting exploratory basic research parsing the complex effects of structural racism into sub-components and their impact on neurocognition, with an emphasis on informing preventive interventions. In addition to neuroscience/psychology, supported projects are expected to integrate expertise, as needed, from epidemiology, intervention science, community stakeholders, and/or critical race theory. Supported projects would incorporate a multidimensional approach to understanding structural racism, including factors such as income inequity, homeownership inequity, employment inequity, education inequity, incarceration inequity, and neighborhood segregation. 

Vani Pariyadath, Ph.D., Chief, Behavioral and Cognitive Neuroscience Branch, Division of Neuroscience and Behavior


Center to Support Research on Racial Equity and Health Disparities

Posted February 2022

Background

In July 2020, NIDA launched the Racial Equity Initiative (REI), a multi-pronged effort to (1) address research gaps and opportunities; (2) develop the addiction science workforce to include more underrepresented minorities (URM); and (3) ensure equity, diversity, and inclusion in NIDA’s workplace climate.  Through the REI, NIDA has committed to allocate $100 million over the next 10 years to support research related to advancing racial equity in addiction science.  For the 2023 fiscal year, research concepts have been proposed to meet the goals of strengthening NIDA’s investment in achieving equity for diverse populations.

Goal

The goal of the Center is to provide scientific, technical, and logistic support for the projects funded under NIDA’s REI funding opportunity announcements.  These projects are intended to support NIDA’s efforts to eliminate disparities related to substance use and substance-related HIV in diverse communities.  The Center is designed to maximize the impact of the funded REI projects by providing logistical support, infrastructure for collaboration, and resources to enable high-quality community-engaged science.  The Center will be staffed with experts who can provide consultation on theoretical, measurement, data management, and operational challenges faced by REI research project teams.  The Center investigators will produce scholarly products related to health equity research for the benefit of REI investigators and the larger scientific community.  The Center’s resources will enable broad dissemination of research findings to the scientific community and to diverse groups of stakeholders. The staff of the Center will develop inward- and outward-facing materials and technical resources, connect investigators studying topics related to substance use disparities across career stages, and produce events/activities to strengthen research on racial equity.  

Aria Crump, Sc.D., Deputy Branch Chief, Prevention Research Branch, Division of Epidemiology, Services, and Prevention Research


Training and Diversifying the Data Science Workforce for Addiction Research 

Posted February 2022

Background

There are three inter-related issues that led to this concept: 1) The importance of increasing the capacity of experts in computation, data science, and related fields to move into the biomedical research space is being acknowledged at NIH and beyond. This idea is outlined in the NIH Strategic Plan for Data Science and there are currently multiple strategies to enhance the data science workforce at NIH, expand the national research workforce, and engage a broader community in the biomedical and clinical research fields. 2)There is an increased focus recently on broadening the benefits of AI/ML technologies to reduce health disparities and inequities. There has been a rapid increase in the volume of data generated through EHR and other biomedical research which is presenting exciting opportunities for developing data science approaches for biomedical research and improving healthcare. 3)There is a lack of diversity of both data and researchers in the AI/ML field. This is a major problem which also has had an increased focus, as it runs the risk of creating and perpetuating harmful biases in its practice, algorithms, and outcomes, which can inadvertently cultivate health disparities and inequities. 

However, there are several challenges that hinder more widespread use of AI/ML technologies, including cost, capability for widespread application, and access to appropriate infrastructure, resources, and training. The lack of diversity of both data and researchers in this field and the risks that lead to health disparities and inequities, but another critical issue is that underrepresented groups often lack financial, infrastructural, and training capacity to apply data science approaches to research questions of interest to them.

Goal

There are many opportunities to leverage the potential of AI/ML to accelerate innovation in biomedical research and it is critical to prioritize and address health disparities and inequities. These mutually beneficial partnerships can be established to increase the participation of underrepresented researchers and communities. It is also critical to provide support for meritorious research, strengthen the research environments and collaborations for successful data science projects, and expose undergraduate and/or graduate students in such environments to meritorious research in this area. 

These are the areas of focus:

  • Utilize AI/ML for health disparities and inequities research specific to addiction
  • Form partnerships/collaborations to provide infrastructure and resources for AI/ML applications and research, particularly for underrepresented groups
  • Identify resources and training needed for data science of addiction research, particularly AI/ML approaches and at institutions that serve under-represented minorities

Susan Wright, Ph.D., Health Scientist Administrator, Division of Neuroscience and Behavior


Transformative Research on the Basic Mechanisms of Polysubstance Use in Addiction

Posted February 2022

Background

A vast majority of research on substance use disorders (SUDs) is focused on individual substances in isolation even though most users of addictive substances engage in polysubstance use. Polysubstance use, defined as the use of more than one addictive substance within a defined interval, may be sequential (use of multiple substances on separate occasions), or concurrent/simultaneous, and is often associated with higher relapse and mortality rates compared to the use of a single substance. Limiting studies to individual addictive substances overlooks interactions between substances and may influence the translatability of preclinical research findings.

Results from several studies have demonstrated that the use of multiple addictive substances produces pharmacokinetic and behavioral profiles that are distinct from those produced by a single substance. Despite this understanding, little is known about the precise pharmacological mechanisms and interactions that may contribute to such outcomes, or co-morbidities resulting from co-use. Even less is known about brain mechanisms at the genomic or circuit levels that contribute to the behavioral and pharmacological profiles observed following polysubstance use.

Goal

This initiative seeks to go beyond the phenomenology of polysubstance use across different classes of addictive substances, patterns of use and subjective effects to seek ideas that will transform our understanding of polysubstance use at the basic molecular, neurobiological, and/or behavioral level. The initiative will be limited to research projects that test novel, exploratory, and mechanistic hypotheses. Projects may focus on combinations of addictive substances with high translational and public health relevance. Studies may investigate basic mechanistic hypotheses in any phase of the substance use trajectory.

Sunila Nair, Ph.D., Program Officer, Division of Neuroscience and Behavior


Chemical Countermeasures Research Program Initiative: Research on Counteracting the Deleterious Effects of Acute Opioid Exposure

Background

National Institute on Drug Abuse (NIDA) in partnership with National Institute of Allergy and Infectious Diseases (NIAID) is committed to advancing the national biosecurity program on counteracting the deleterious effects of acute opioid exposure and strengthening the national medical and public health preparedness systems further during and after mass casualty emergencies resulting from the deliberate and/or accidental release of synthetic opioids1.
Synthetic opioids such as fentanyl have been designated as high consequence, highly toxic chemicals of concern by the Department of Homeland Security (DHS)2 and Department of Defense (DOD)3. Fentanyl and its analogues when used in weaponized form or by accidental exposure of illicit caches, have the potential to produce mass casualties.  The currently available opioid antidote naloxone is less effective for reversing the overdose effects of fentanyl and its congeners such as carfentanil. Emergency responders would typically need to administer naloxone multiple times, which in the case of mass casualty events severely limits its therapeutic application. There is an urgent need for identifying post-exposure/overdose treatments that can be easily and rapidly deployed in the field to counteract the deleterious effects of opioids. Moreover, acute toxic exposure to such opioids can potentially lead to a sequela of non-lethal effects that can persist from days to months after exposure. Survivors of these events may experience intermediate complications followed by persistent long-term debilitating effects. There is hence a need for identifying potential treatment options for chronic morbidities that may arise following acute exposure to opioids as well.

1) National Institutes of Health (NIH) Executive Meeting Summary: Developing Medical Countermeasures to Rescue Opioid-Induced Respiratory Depression (a Trans-Agency Scientific Meeting)-August 6/7, 2019 2) S&T Master Question List for Synthetic Opioids | Homeland Security (dhs.gov) 3) Synthetic Opioids: A New Class of Chemical Weapons? – HDIAC

Goal

This NIDA-led concept will support cutting-edge research to identify novel therapeutic targets and approaches leading to medical countermeasures (MCMs) that can reverse life-threatening events caused by acute opioid poisoning/overdose, are easy to administer in a mass-casualty situation and are effective as post-exposure therapies. Additionally, this concept will support mechanistic research aimed at understanding and treating the delayed or persistent effects of acute opioid exposure.

Kiran Vemuri, Ph.D., Program Officer, Division of Neurosciences and Behavior


NIH BRAIN Initiative: Brain & Behavioral Quantification and Synchronization

Posted February 2022

Background

Major advances in technology and computational approaches have advanced the study of brain structure and function.  Yet while current neurocognitive research designs typically capture high-resolution neural data, this often occurs in settings that do not solicit or capture complex, adaptive behavior.  Fortunately, there are now tools available that allow for high-resolution, multimodal measurement of behavior that, through computational modeling, can be integrated with simultaneously collected information about the physical, cognitive, and social environment in which the organism is embedded.   Using these advanced approaches, it is possible to develop theoretical and computational models that capture the full complexity and adaptive value of behavior and can lead to more complete and valid models of neurobehavioral function and its alteration by environmental and biological risk factors relevant to illnesses such substance use disorders.

Goal

The Brain-Behavioral Quantification and Synchronization initiative would advance basic research that 1) applies the most innovative technologies to collect high-resolution, multimodal behavioral and physiological data from organisms while also tracking changes in the complex environments in which the organisms are embedded; and 2) develops novel computational modeling approaches to integrate these multiplex data and reveal new insights about behavior.  Behavioral data that could be collected from the organism could include geographic location, posture and muscle configurations, autonomic function, respiratory patterns, speech and other sonic emissions, olfactory signals, and more.  These data would be synchronously collected with data reflecting physical changes and social signals in the organism’s environment.  Research designs that integrate cognitive, ethological, and evolutionary behavioral theories would be encouraged, as would diversity in the species to be studied. An emphasis would be placed on linking organismal and environmental data across levels of analysis collected to develop new computational and predictive models of neurobehavioral function as part of a dynamic complex system interfacing with the organism’s environment. 

Holly Moore, Ph.D., Health Science Officer, Division of Neuroscience and Behavior


Large Scale Integrated Mapping and Molecular Profiling of Cell Ensembles Mediating Opioid Action in the Rodent Brain

Posted February 2022

Background

Since its first issuance in 2020, this program supports research that employs innovative scalable technologies to map molecularly-, functionally- and anatomically-defined cell assemblies that mediate responses to opioids in the rodent brain. Studies have combined a variety of single-cell and spatial transcriptomics approaches, live and volumetric imaging, and tracing technologies, in the context of various drug administration regimens and behaviors. As the body of data generated expands, opportunities will emerge to derive knowledge through analyses that integrate datasets across multiple studies and data modalities. To be amenable to such integrated analyses, datasets must be made findable, accessible, interoperable, and reusable (FAIR).

Goal

The long term goal of this program is to enable the generation of a molecularly anotated atlas of the cell assemblies and cell-types that mediate responses to opioids. This concept will support the continuation of the experimental studies and data collection effort initiated in 2020 and will develop related data center component(s) through a new companion concept. The data center component(s) will make this resource publically available, FAIR and compatible with SCORCH and BRAIN initiative databases, to enable joint secondary analyses by the scientific community.

The tasks of the new data center component(s) will comprise: 1) developing standards and definitions for drug administration regimens and behavioral assays, 2) facilitating and coordinating the intake of data and metadata, 2) enabling data registration into a brain common coordinate framework, 3) developing pipelines for analytics and archiving and 4) promoting the use and dissemination of datasets derived from these concepts.

The program(s) will be designed to handle large datasets comprising time-series from live-imaging or neurophysiology experiments and associated behavioral datasets, as well as serial and 3D morphoanatomical images and data. The program(s) will also need to interface with the existing SCORCH data center, that processes and archives single-cell resolution omics data, generated under the NIDA Single Cell Opioid Responses in the Context of HIV (SCORCH) consortium and other NIDA-funded programs. 

Olivier Berton, Ph.D., Acting Branch Chief, Integrative Neuroscience Branch, Division of Neuroscience and Behavior


Leveraging Cutting-Edge Cell Lineage and Connectivity Tracing Approaches to Chart the Effects of Addictive Substances on Brain Development at Cellular Resolution

Posted February 2022

Background

ABCD and HBCD studies provide unique windows into normative brain development, and how it is impacted by exposure to addictive substances and other environmental factors. However, insights into the biological and cellular underpinnings of these observations remain limited in humans. Even in model species, we lack comprehensive quantitative descriptions of the effect of addictive drugs on spatially-and temporally-resolved developmental trajectories of brain cell-types.

Novel scalable approaches, such as the ones emerging from the BRAIN initiative, offer means to chart temporally-resolved changes in the molecular and connectomic properties of cell-types in the developing brain. Examples include single-cell multiomics and spatial transcriptomic technologies, novel viral-based and affinity tools for high-throughput connectomics compatible with tissue clearing and volumetric imaging and new cell lineage tracing methods. 

Goal

This concept will support the application of such innovative cell-lineage and connectivity tracing approaches to quantitate the effects of addictive substances on the developmental trajectories of cell-types in the rodent brain, in vivo. Projects may sample the entire period of embryonic and postnatal brain development and may investigate the effects of any addictive substance with high translational and public health relevance.

Olivier Berton, Ph.D., Acting Branch Chief, Integrative Neuroscience Branch, Division of Neuroscience and Behavior


Novel Drug (DDT) and Medical Device Development Tools (MDDT) to Help Expedite Creation and Regulatory Approvals of New Therapies for Substance Use Disorders (SUD)

Posted February 2022

Background

All medical products including drugs, biologics, and devices must obtain FDA approval before being marketed in the United States. However, there is a disconnect between current practices in SUD research and the corresponding regulatory science used by FDA in decision making. Successful approval of future SUD therapeutic and diagnostic products will require better understanding of the SUD research tools, which can be achieved through the FDA tool qualification programs aimed to support assessment of future SUD regulatory submissions. The FDA has established two programs, the CDER/CBER Drug Development Tool (DDT) and the CDRH Medical Device Development Tool (MDDT) whereby new tools that are “qualified” (i.e. accepted) by FDA can be relied upon to have a specific interpretation and application in medical product development and regulatory review. Notably, qualified tools can be commercialized and used by multiple sponsors to accelerate drug and device development and evaluation. Once qualified by FDA, the Tool can be used within the qualified Context of Use (COU) to support any regulatory submission for drugs/biologics (DDT) and medical devices (MDDT) without submission of additional information to justify the use of the DDT or MDDT.

Neither the DDT nor the MDDT program currently includes tools that have a COU specific to SUD. The national SUD crisis is time-sensitive and requires action to speed up research and approval of new treatment options. By supporting development of DDTs and MDDTs, this FOA will help expedite approval of novel drugs/devices by establishing pre-approved tools that grantees can use in their product development and testing. These tools will assist companies to address the urgent need for safe and effective novel solutions for SUD patients and represents an important and timely opportunity.

Goal

The goal is to support research to advance drug and device development tools for submission to the DDT or MDDT tool qualification program within either FDA’s CDER or CDRH, respectively. Once qualified, these tools will be available to fill unmet needs in SUD research and biomedical product development.

Proposals may include development of any of the following drug or medical device development tools as defined by FDA: validated biomarker(s); non-clinical assessment models including animal, ex-vivo, or computational models; or clinical outcome assessments (COA) including patient-reported outcome (PRO), observer-reported outcome (ObsRO), clinician-reported outcome (ClinRO), and performance outcome (PerfO) measures.

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


Therapeutic Development of Psychoplastogenic Compounds for Substance Use Disorders

Posted February 2022

Background

The fifth edition of The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) is a diagnostic manual utilized by clinicians that contain descriptions and symptoms of mental disorders, including substance use disorders (SUD). SUDs have defined a collection of chronic disorders initiated by the misuse of legal and illicit drugs, then potentially leading to an uncontrollable drug-seeking behavior in a SUD. The neuroimaging studies of SUD patients have observed abnormal prefrontal cortex (PFC) function. The PFC can regulate the ability of the limbic reward circuitry, modulate attention, and can apply top-down regulation over drug-seeking behavior. Investigations of improving PFC function including non-pharmacological interventions showing some success for treating SUD. A promising new drug class of psychoplastogens includes a growing list of fast-acting therapeutics that promote structural and functional neural plasticity. The development of these compounds would be capable of modifying the PFC neural circuits to help control the SUD drug-seeking and anxiety-related behavior. 

One of the members of the Psychoplastogenic compounds (PC), Ketamine has gone from a historically used anesthetic compound to expand the clinical use as a novel fast-acting antidepressant medication.  Other PC compounds include the natural and synthetic class of drug psychedelics which are being investigated as a therapy for the CNS disorders of major depression and post-traumatic stress syndrome. Recently there have been three companies developing PC drugs for CNS indications that have been having launched multimillion-dollar initial public offerings (IPO) demonstrating, the area has matured and there is considerable business interest in this drug class. This Funding Opportunity Announcement (FOA) invites applications to validate PC based pharmacotherapeutics for the treatment of a SUD.  Applications focusing on alcohol use disorder or pain as the primary indication will not be supported under this National Institute on Drug Abuse (NIDA) funding opportunity.

Goal

Research Questions:

Applications developing or utilizing natural or synthetic PC-based compounds in the following areas for Substance Use Disorders (SUD) drug discovery and development are encouraged and may include:

  • Target Identification and Validation Studies
  • Investigation of bioactive natural products, related extracts, and the identification of key active compounds for efficacy and toxicity in in vitro assays (e.g., on and off target) and preclinical in vivo SUD models;
  • Synthesizing, purifying, and testing synthetic PC candidates for efficacy and toxicity in in vitro assays (e.g., on and off target) and preclinical in vivo SUD models; Additional medical chemistry activities to improve hit to lead development (e.g., solubility, metabolism, remove off-targets activities)
  • Assay Development and hit to lead activities-
  • Target and phenotypic screening of PC based compounds, hit confirmation and validation. 
  • Lead optimization studies
  • Performing preliminary pharmacokinetic (PK) and pharmacodynamics (PD) analyses
  • Preclinical development for efficacy and safety in animals;
  • Testing and validation of efficacy in in vitro or in vivo models (e.g., rodents, nonhuman primates);
  • Optimization of dose, dosing interval, and route of delivery in preclinical evaluation or in animal models; Methods to modify existing drugs/therapeutics to improve economy of production, half-life in vivo, target affinity, potency, clearance rates, or tissue accessibility; or to decrease adverse side effects of administration; Assessing bioavailability and mechanism of action.

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


Enabling SUD Digital Therapeutics Research to Improve Payor Adoption

Posted February 2022

Background

When a biomedical product is being developed and brought to the market, it must meet the needs of multiple stakeholders to be successfully adopted. This includes regulatory agencies (FDA), payers (CMS and private insurers), medical providers, and patients. However, each stakeholder is focused on different outcomes. Payers base their reimbursement decision predominantly on the health benefits of the product in comparison to existing treatment options and cost-effectiveness. To be successful, the biomedical product sponsor must factor all stakeholders in their product development strategy and clinical trial design early on in the process.

This paradigm of incorporating all stakeholders' needs into the development process is even more critical for companies developing digital therapeutics to treat substance use disorder (SUD). Digital therapeutics is a digital health category defined as products that “deliver evidence-based therapeutic interventions to patients that are driven by high-quality software programs to prevent, manage, or treat a medical disorder or disease.” Currently, there are two FDA-approved digital therapeutics for the treatment of SUD and opioid use disorder (OUD). However, despite FDA approval, adoption by providers and patients remains lower than hoped, partly due to a lack of payer reimbursement. The payer approval process usually comes after FDA/regulatory approval, and the reimbursement process typically includes three separate elements: coding, coverage, and payment. There are two reasons for the poor adoption of digital therapeutics; the first is the lack of CPT codes for SUD digital health. The second is a lack of long-term efficacy and patient outcome data (e.g., in the De Novo Classification Request for reSET, the company presented abstinence at weeks 9-12 as the primary endpoint) and a favorable impact on the quality-adjusted life-year (e.g., the Institute for clinical and economic review conducted an evaluation of digital health technologies for the treatment of opioid use disorder and concluded that the current price of the interventions, at best, represents a low long-term value).

To ensure that digital therapeutics that have been or are in the development process for SUD treatment are adopted, this funding opportunity concept aims to fund clinical trials that will generate data that is convincing for payers to support adoption. In addition, because FDA approval is not always necessary for digital therapeutics to be included in digital formularies (e.g., Express Scripts and CVS Health, the two largest pharmacy benefit management companies that account for 56% of all prescription claims), projects that specifically meet the pharmacy benefit management requirements will also be considered.

Goal

The goal is to support applications validating digital therapeutics research to promote payor/pharmacy adoption and reimbursement for the treatment of Substance Use Disorder (SUD). Types of studies may include: 

  1. Creating a data package for existing digital therapeutics to meet requirements of digital formularies
    • Clinical effectiveness, user experience, security and privacy compliance, and value and affordability
  2.  Creating a data package for existing digital therapeutics to meet requirements of CMS and private payors

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


Leading Addiction, Diversity, and Discovery in Education and Research (LADDER)

Posted February 2022

Background

The purpose of this program is to create new partnerships and collaborations between under-resourced universities (including Minority Serving Institutions) and the National Institute on Drug Abuse (NIDA) T32 funded institutions to jointly train substance use disorder researchers.  To achieve this goal, support will be provided to eligible domestic institutions that historically serve underrepresented and underserved populations or are in (IDeA)-eligible states (referred to as the home institution) to provide high quality training and mentoring that will prepare and empower scholars to lead the nations’ future substance use and addiction research workforce. Home institutions will partner with one or more NIDA funded T32 programs which would provide summer research experiences. In turn, T32 institutions can use this opportunity to diversify their T32 appointments as well as student body and research programs at large. The proposed research training programs will incorporate didactic, research experiences (in-person and/or virtual), mentoring, and career development elements to prepare trainees to transition to next career stage in substance use and addiction research. 

Goal

  • The purpose of this program is to provide funding for research resources to under-resourced universities for equipment and related costs;
  • Ensure that there is a diverse pool of undergraduate and graduate students who complete their degree, and successfully transition into substance use and addiction research-focused programs (e.g., Ph.D., or M.D./Ph.D., or postdoctoral fellowships) at NIDA funded research intensive institutions;
  • Promote the creation of new partnerships and collaborations between under resourced universities with NIDA T32 funded institutions. 

Albert Avila, Ph.D., Director, Office of Diversity and Health Disparities


Research Opportunities for New and At-Risk Investigators to Promote Scientific Workforce Diversity

Posted February 2022

Background

NIDA recognizes that there are many benefits to fostering a diverse workforce, for example promoting diversity of scientific ideas, understanding different perspectives from researchers, and maintaining cultures of inclusive excellence in the NIDA research community. When scientists from different backgrounds work together, their unique perspectives and experiences stimulate creativity and innovation, yielding higher quality research than less diverse teams. Importantly, diverse research teams are more likely to ensure that members of underserved populations will support and participate in research, and that the research NIDA invests in addresses questions that are meaningful to these communities.

NIDA recognizes a unique and compelling need to promote diversity in the biomedical, behavioral, clinical and social sciences workforce. The NIH expects efforts to diversify the workforce to lead to the recruitment of the most talented researchers from all groups; to improve the quality of the educational and training environment; to balance and broaden the perspective in setting research priorities; to improve the ability to recruit subjects from minority and other health disparity populations into clinical research protocols; and to improve the Nation's capacity to address and eliminate health disparities. For more information, see Notice of NIH's Interest in Diversity, NOT-OD-20-031

Goal

The overarching goal of this program is to enhance the diversity of New and At-Risk Investigators conducting research within the mission of NIDA. Fostering diversity by addressing underrepresentation in the scientific research workforce is a key component of the NIH strategy to identify, develop, support, and maintain the quality of our scientific human capital. Despite tremendous advancements in scientific research, information, educational and research opportunities are not equally available to all. NIH encourages institutions to diversify their student, postdoctoral, and faculty populations to enhance the participation of individuals from groups identified as underrepresented in the biomedical sciences (e.g., see Notice of NIH's Interest in Diversity, NOT-OD-20-031).

This program is intended to support the research of New and At-Risk Investigators from diverse backgrounds, including those from groups underrepresented in the health-related sciences. Principal Investigators (PIs) from categories A-D listed in the NIH Diversity Statement are especially encouraged to apply.

Albert Avila, Ph.D., Director, Office of Diversity and Health Disparities


Reaching Equity at the Intersection of HIV and Substance Use: Novel Approaches to Address HIV Related Health Disparities in Minority Populations

Posted September 2021

Background

The CDC estimates that HIV infections have declined by 8% from 2015-2019, but persistent disparities remain. Black/African American and Hispanic/Latino men who have sex with men (MSM), African American/ Black women, and transgender persons of color, continue to be disproportionately affected. The public health policies and guidelines to expand the reach of HIV prevention and care services so far have had little impact on the communities that continue to be disproportionately affected by HIV. For example, Pre-Exposure Prophylaxis (PrEP) is prescribed less, and PrEP awareness and uptake is persistently lower among African American and Latino men compared with white men. Comprehensive health care policy reform laws, including the Affordable Care Act and expanded Medicaid, have not sufficiently addressed gaps in access to and uptake of HIV prevention and care among these heavily impacted populations. Addressing these disparities requires more than broad-based public health initiatives targeting increased access in general, or blanket approaches to expanding resources. Substance use continues to be a major driver of new HIV diagnoses, yet there is less attention to contemporary drug use patterns (e.g., use of cocaine and methamphetamine) that contribute to increased HIV risk, namely sexual risk behavior, among racial/ethnic minorities.

Goal

Stimulate new ways of understanding and addressing structural factors, organizational practices, policies, and other social, cultural, and contextual influences that lead to inequities at the intersection of HIV and substance use among racial/ethnic, sexual and gender minority populations. This initiative will focus on:

  1. A deeper understanding of how social and structural factors interact to perpetuate or ameliorate health inequities in HIV and SUD outcomes for racial/ethnic minorities and other populations with above average rates of HIV incidence and prevalence.
  2. Development, implementation and testing of novel interventions or strategies that focus on social, structural, policy and cultural factors, to reduce health disparities and lead to equity in HIV and SUD prevention, treatment, and care among high-risk populations.

Sheba Dunston, Ed.D., MPH, CHES, Division of Epidemiology, Services, and Prevention Research


Enhancing Social Connectedness and Ameliorating Loneliness to Prevent and Treat SUD and Support Recovery

Posted September 2021

Background

Surgeon General Vivek Murthy has been touting loneliness as a public health crisis and has said that “we will not solve the addiction problem in America if we don’t address social connection.” Social connectedness is the subjective feeling of belonging, while loneliness is the subjective feeling derived from an incongruency between one’s desired level of meaningful relationships and the perception of one’s actual relationships. Enhancing social connectedness can decrease feelings of loneliness, which can predict of a range of health problems, including substance use. While it is widely accepted that all phases of the substance use trajectory, from initiation through recovery, are associated with feelings of connectedness and loneliness, few interventions have tested the influence of social connectedness or loneliness on substance use, the development of SUDs, treatment continuity, relapse, or recovery. Interventions to enhance social connectedness and reduce loneliness have been developed and tested, but not applied to substance use prevention, treatment, or recovery.

Goal

This initiative aims to stimulate intervention research on substance use prevention, treatment, and recovery by targeting social connectedness and feelings of loneliness. Applicants will be encouraged to think creatively and consider a wide range of intervention targets. This initiative will focus on:

  1. Conducting intervention research that helps build a unified theory of the role of loneliness and social connectedness in substance use prevention, treatment, and recovery.
  2. Adapting existing loneliness interventions used in other fields of public health or enhancing existing substance use interventions by adding loneliness and social connectedness components.

Carrie Mulford, Ph.D., Division of Epidemiology, Services, and Prevention Research


Registry of Medical Cannabis Use and Health Outcomes

Posted September 2021

Background

As of May 18, 2021, 36 US states and four territories allow for the medical use of cannabis products. Current evidence from global database registries and other patient reported outcomes incorporate information from thousands of patients, but much of the evidence is based on anecdotal reports rather than possessing the robustness of randomized clinical trials, and these different types of sources are not always in agreement. A 2017 Institute of Medicine Report included several recommendations “to address research gaps, improve research quality, improve surveillance capacity, and address research barriers” as related to medical use of cannabis. One of these recommendations is to develop an evidence base on the short- and long-term beneficial and harmful effects of cannabis use.

Goal

The goal of this cannabis registry is to gather information regarding medicinal cannabis products used as well as timing of, reasons for, and outcomes of use and impacts on other non- cannabis medication (e.g., opioids) use. This information will allow for evaluation of patterns of use, real-time conditions around use, and biochemical validation of use. To maximize the analytic utility of these data by the research team as well as external researchers, the registry team will develop a repository/archive for these data. In addition to data collection, the team will synthesize and analyze data to determine parameters and characteristics that may be useful for physicians to provide recommendations to patients as well as to policymakers to improve safer use conditions. In addition, the team will ensure that these analytic products reach target audiences.

Heather L. Kimmel, Ph.D., Health Scientist Administrator, ERB/DESPR


Research Adoption Partnerships

Posted September 2021

Background

Despite significant research investment, evidence‐based practices addressing opioid use disorder (OUD) and pain are underutilized. Barriers include stigma, inequity in treatment reimbursement, lack of provider education, and system‐level policies. New approaches are needed to build partnerships among researchers and public/private sector stakeholders to help overcome these barriers to adopting evidence‐based practices for preventing and treating OUD.

Goal

The goal of this initiative is to establish a mechanism to inform, disseminate, and implement research findings to address barriers to evidence-based practices. Priority goals include:

  • Establish a national resource center to promote equitable dissemination and implementation of evidence‐based practices addressing the opioid crisis – leveraging partnerships with stakeholders, existing infrastructure, and implementation experts
  • Conduct original trials of implementation strategies in multiple systems of care (health plans, specialty care, public health systems)

Tisha Wiley, Ph.D., Division of Epidemiology, Services, and Prevention Research


Actionable Data to Inform Research‐Driven Decisions (HEAL Initiative Data2Action)

Posted September 2021

Background

Over the last year, the US saw a 30% increase in overdose deaths, totaling the largest number of annual overdoses in history, with 62% linked to synthetic opioids like fentanyl. While overdoses are rapidly increasing, lags in data availability (months or years) hamper efforts to proactively prepare for – or even nimbly react to – overdose surges. There is a need for actionable data to provide a precise picture of trends in opioid use and overdose in communities. Even if data lags are addressed, there are questions of who and how these data will be used to facilitate responses at national, state, and local levels. Enhanced methods of collection, new tools, technologies, or strategic access could offer data sources to inform implementation, to enhance available resources, or reduce opioid use and overdoses.

Goal

The goal of this concept is to attract researchers who have data in hand and new or existing tools or methods to conduct predictive analyses to 1) use data sources that accessible and analyzed on a timescale allowing for predictive and proactive responses and 2) leverage partnerships with key stakeholders to turn research results directly toward decisions and implementation.

Tisha Wiley, Ph.D., Division of Epidemiology, Services, and Prevention Research


Real‐World Data to Address Urgent OUD/SUD Needs

Posted September 2021

Background

Although opioid prescriptions declined since their peak in 2015, the consequences of the opioid crisis are far from over. Polysubstance misuse involving illicit opioids and psychostimulants has become a dangerous fourth wave in the opioid epidemic. Since 2020, social distancing, job loss, and other adverse stresses resulting from COVID‐19 exacerbated the complex OUD and SUD epidemics. Overdose deaths increased 29% in 2020 to approximately 93,000 (preliminary data CDC July 2021). Numerous data sources exist that capture various aspects of these trends. However, challenges exist in linking and leverage these existing “real world” data in ways that can be used to provide real‐time or near‐real time understanding to the constantly changing drug overdose epidemic.

Goal

This project will encourage development of new methods and approaches to update and aggregate data from existing sources (i.e., EHR, claims data, registry data, pharmacy dispensing, and mortality records, etc.) Such visibility could provide new insights into the dynamics of substance use, addiction, recovery, and relapse.

Tisha Wiley, Ph.D., Division of Epidemiology, Services, and Prevention Research


Sequencing Resource for Molecular Genetics and Epigenetics of Addiction

Posted September 2021

Background

The purpose of this concept is to provide RNA and DNA sequencing resources to scientists investigating the molecular genetics and epigenetics of addiction. Modern molecular genetics requires extensive sequencing resources to identify causal variants identified in GWAS studies, to identify rare variants from whole genome sequencing, to run single cell RNA seq studies, to execute 3-dimensional chromosome assays, and to identify promoters and enhancers in open chromatin using methods such as Cut and Run. Long-read sequencing has the potential to identify the causal role of transposable elements and other repetitive elements in somatic and germ-line mutations.

Goal

The goal is to create a central sequencing resource run by a government lab to keep costs down. Expenses are kept down because personnel cost is already budgeted, and economies of scale drive the prices of reagents lower. Access would be granted to investigators who have already had their grant peer-reviewed, or the request would be peer reviewed for investigators requesting sequencing whose request has not gone through peer review.

Jonathan D. Pollock, Ph.D., Chief, Genetics, Epigenetics, and Developmental Neuroscience Branch, Division of Neuroscience and Behavior


NIDA Center for Genetic Studies

Posted September 2021

Background

Substance use disorders (SUD) comprise a broad category of complex phenotypes that constitute a major public health challenge. The etiology of SUD encompasses genetic and environmental components, hampering the identification, validation, replication, and functional assessment of genetic-based therapeutic targets. However, new technological and scientific breakthroughs hold tremendous promise to tease out the underlying genetic and epigenetic signatures associated with SUD, including single nucleotide polymorphisms (SNPs), chromatin interactions, gene expression differences, rare variants, copy number variants, functional SNPs, indels and large chromosomal rearrangements. These technological advances, along with emerging methods to measure environmental exposures and generate human reprogrammed cellular derivatives (i.e., induced pluripotent stem cells (iPSC), have the potential to increase our understanding of the etiology of SUD and accelerate the development of new therapeutic compounds and predictive/diagnostic tests.

For SUD and other genetically complex diseases with modest genetic effect sizes, data sharing is often necessary to achieve sample sizes with adequate statistical power to detect genetic associations and prioritize potentially causative mutations. The NIDA Center for Genetic Studies (NCGS) will reduce the overall cost both to NIDA and to NIDA's investigators funded to do research on the genetics of SUD by centralizing the storage and analysis of these samples, facilitating a negotiated reduction in price due to the volume of work and creating a large genomic data repository and biobank that can be accessed by investigators for research purposes.

Goals

The goal of this concept is for the NCGS to facilitate research projects on genetics of drug addiction vulnerability. The center will achieve this goal by:

  1. Receiving, processing, genotyping, and sequencing human samples from SUD studies at a reduced cost.
  2. Serving as a centralized repository for all samples that can be distributed to investigators to conduct SUD research.
  3. Maintaining a state-of-the art database to house the samples and their associated data, which investigators can access for secondary analysis research. All data will be maintained according to FAIR standards (Findable, Accessible, Interoperable, and Reproducible) for the SUD research community.

Jonathan D. Pollock, Ph.D., Branch Chief, Genetics, Epigenetics, and Developmental Neuroscience, Division of Neuroscience and Behavior


Avenir Award Program for Genetics or Epigenetics of Substance Use Disorders

Posted September 2021

Background

Avenir means future in French, and this award supports early-stage investigators proposing highly innovative studies who may lack the preliminary data required for an R01 grant. The award program targets proposals showing principal investigators with promise of being tomorrow's leaders in the field. The precedence for this award has been established by previous NIDA Avenir Award Programs.

Goal

The Genetics or Epigenetics of Substance Use Disorders Avenir Award program supports studies that open new areas of research for the genetics or epigenetics of addiction. These studies may develop novel methods or approaches that can potentially be applied to the analysis of the genetics or epigenetics of addiction. Investigators outside the field of addiction interested in applying their approaches to the genetics or epigenetics of addiction are encouraged to apply.

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


Exploiting Novel Genomic or Epigenomic Tools to Functionally Characterize Genes or Variants Relevant to Substance Use Disorders

Posted September 2021

Background

Extremely powerful genomic tools and strategies continue to be developed and improved by independent investigators or as a part of larger projects supported by BRAIN, NIH Common Fund, or other entities. Examples include CRISPR gene editing and CRISPR epigenome editing which can be used to alter genome structure or influence epigenomic regulation. It is important that these tools are used to investigate questions relevant to substance use disorders (SUDs).

Goal

The goal is to support projects which exploit novel genomic or epigenomic tools, including CRISPR-based genome or epigenome editing tools, to functionally characterize genes, genetic variants, or epigenetic variants relevant to SUDs. It is hoped that such studies will accelerate the investigation of the neurobiological mechanisms of SUDs and provide critical foundational knowledge for the development of future prevention, diagnostic, or therapeutic strategies. It is expected that any resources, tools, or data generated will be made broadly available to the scientific community.

John Satterlee, Ph.D., Health Scientist Administrator, NIDA Division of Neurobiology and Behavior


Avenir Award for Chemistry and Pharmacology of Substance Use Disorders

Posted September 2021

Background

NIDA’s Avenir Awards provide grants to early-stage investigators who propose highly innovative studies. “Avenir” is the French word for “future”, and these awards represent NIDA’s commitment to supporting researchers who represent the future of addiction science. NIDA currently has two Avenir award programs, one for HIV/AIDS and another on the genetics and epigenetics of substance use. However, recent advances in methods and technologies for identifying novel pharmacological targets, mechanisms, and pathways could improve research on treating substance use disorders. Emerging methods such as virtual screening of large libraries of compounds, design and screening of DNA encoded libraries, application of rational drug design, targeted protein degradation, and click chemistry are quickly advancing the field. Additionally, machine learning/artificial intelligence methods for identification of chemical probes and for the de novo design and optimization of lead molecules are accelerating the drug discovery and development process.

Goal

By creating an Avenir Award for Chemistry and Pharmacology of Substance Use Disorders, this initiative will expand the opportunities for exploring novel chemical and computational approaches for target identification. This award will support early-stage investigators proposing transformative research in the field of chemistry and pharmacology of substance use disorders. Their research may focus on developing novel chemical and pharmacological methods or approaches to the study of basic biological mechanisms, pathways, targets, and drugs of relevance to substance use disorders and addiction.

Sam Ananthan, Ph.D., Division of Neuroscience and Behavior


Workshops on Computational and Analytical Research Methods

Posted September 2021

Background

Neurocognitive studies have undergone transformative changes over the last decade. First, there has been a shift in the field towards pooling together smaller datasets (e.g., ENIGMA) or creating larger ones that are widely disseminated (e.g., Human Connectome Project, ABCD, HBCD). This shift has accelerated machine learning-based efforts towards prediction of substance use and psychiatric outcomes. Second, computational psychiatry has witnessed significant advances in explanatory modeling that seek to uncover neural computations underlying cognition, behavior, and associated dysfunction (e.g., reinforcement learning models applied towards dopamine’s role in reward learning and motivation). While major advancements have been made in the development of rigorous analytical and computational methods, their application in SUD research remains an area for further growth.

Goal

The purpose of this concept is to invite applications that disseminate analytical and computational methodologies and best practices through educational activities with hands-on research experience. The overall goals of this initiative are:

  1. Facilitating collaboration between clinical and computational researchers on SUD research
  2. Enhancing rigor and reproducibility towards better predictive models
  3. Broader application of sophisticated analytical and computational modeling approaches in SUD research
  4. Development of novel solutions to challenges faced in clinical application of computational psychiatry models

Primary: Vani Pariyadath, Ph.D., Chief, Behavioral and Cognitive Neuroscience Branch, Division of Neuroscience and Behavior

Elizabeth Hoffman, Ph.D., Scientific Program Manager (ABCD Project), Division of Extramural Research


NIDA Research Center of Excellence Grant Program

Posted September 2021

Background

Specialized Centers provide an important resource for a diverse range of multidisciplinary research that bring multiple scientific perspectives and approaches to a research area or question. Centers include research components and cores that are linked by an overall theme and integrated in such a way that productivity, quality, and progress exceed those expected from the individual components. A Center is expected to transform knowledge in the sciences it is studying in new and creative directions. Topics in active Research Centers range from basic biological mechanisms associated with opioid and cocaine relapse using rodent and human studies, to understanding the factors that drive health disparities among African Americans, to novel therapeutic approaches to relapse prevention. The continued interest by the SUD research field to use this mechanism remains strong and NIDA has funded several of these centers over the recent years.

Goal

The NIDA Research Center of Excellence Grant Program provides support for research Centers that (1) conduct drug abuse and addiction research in any area of NIDA’s mission, (2) have outstanding innovative science, (3) are multidisciplinary, thematically integrated, synergistic, and (4) serve as national resources to provide educational and outreach activities to drug abuse research communities, educational organizations, the general public, and policy makers in fields of high priority to NIDA. A Center of Excellence is expected to foster the career development and mentoring of new investigators who would be given meaningful roles in Center projects. NIDA Centers should be national community resources for furthering drug abuse research by sharing their findings, their data, and their resources as appropriate for researchers to use and build upon and to advance research in this field.

Kevin Walton, Chief, Clinical Research Grants Branch, Division of Therapeutics and Medical Consequences (DTMC)


Medications Development for Opioid Use Disorder (OUD) and Opioid Overdose (OOD)

Posted September 2021

Background

Treatment for polysubstance use disorder is a public health priority, given the current alarming trends in morbidity and mortality from opioids and other substances, exacerbated by the COVID-19 pandemic. Nearly 40% of opioid-involved OD deaths also involved stimulants, including methamphetamine or cocaine.

Goal

The goal of this initiative is to support research to advance development for FDA approval of safe and effective medications to treat and prevent overdose among individuals with concomitant use of opioids with stimulants (methamphetamine and cocaine) and other substances.

Contact: Ivan Montoya, MPH, MD, Acting Director, Division of Therapeutics and Medical Consequences


Developing Regulated Therapeutic and Diagnostic Solutions for Patients Affected by Opioid and/or Stimulants Use Disorders (OUD/StUD)

Posted September 2021

Background

Over the last 15 years, deaths due to opioid overdoses have exceeded 500,000. Recent studies have shown an increase in stimulant use among people with an existing opioid use disorder (OUD). While there are currently five pharmacotherapies approved by the Food and Drug Administration (FDA)-for the treatment of OUD and mitigation of opioid withdrawal symptoms, there are no FDA-approved medications for Stimulant Use Disorder (StUD). Developing and evaluating new and more efficacious medications remains a high priority. Medical devices, including digital therapeutics, offer promising means to monitor, diagnose, and treat OUD/StUD. Currently, there are only five devices, including software as a medical device, cleared by the FDA for treatment of substance use disorders, including OUD; none of these devices have specific indications for StUD. There are no approved wearable devices for OUD/StUD patients, and diagnostic devices are limited to in-vitro solutions. The investigation and development of new safe and effective medical devices intended for OUD/StUD patients are of high priority.

Goal

Proposals may fall within but are not limited to 1) pharmacotherapeutics (small molecules and biologics) and preventative agents; 2) medical therapeutic and diagnostic devices, including software as a medical device. Biomedical technologies leading to the prevention and treatment of OUD/StUD are highly desired. Small business companies interested in demonstrating that their FDA-regulated product has a potential application in the OUD/StUD space are also encouraged to apply. Proposed approaches are expected to include activities leading to regulatory submissions, including pre-submission meetings, through the appropriate FDA Center. Additional preclinical activities may include but are not limited to computational modeling studies, animal studies, Good Manufacturing Practice studies, Toxicology, biocompatibility studies.

Elena KoustovaPh.D., MBA, Director, NIDA Office of Translational Initiatives and Program Innovations (OTIPI) or Leonardo Angelone, Ph.D., Deputy Director, NIDA/OTIPI


Accelerating the Pace of Drug Abuse Research Using Existing Data

Posted May 2021

Background

This concept was developed to encourage novel analyses of existing data such that prior investments in research are taken advantage of to their fullest extent and findings are disseminated in a timely and cost effective manner. Essential to the success of this concept has been expertise and understanding among review panel members in the complexity and benefits of analysis of existing data, including permissions to use data, harmonization of data, unique insight into etiology gained from analysis of existing data, innovative methods and their impact, multiple units of analysis, and effective and rapid dissemination. The intent of this concept is to capitalize on efficiencies, innovations, and associated benefits of analysis of existing data.

Goal

The goal of this concept is to invite applications proposing the innovative analysis of existing social science, behavioral, administrative, electronic health record (EHR), clinical trials, and neuroimaging data to study the etiology and epidemiology of drug using behaviors (defined as alcohol, tobacco, prescription and other drug) and related disorders, prevention of drug use and HIV, and health service utilization. This FOA encourages the analyses of public use and other extant community-based or clinical datasets to their full potential in order to increase our knowledge of etiology, trajectories of drug using behaviors and their consequences including morbidity and mortality, risk and resilience in the development of psychopathology, strategies to guide the development, testing, implementation, and delivery of high quality, effective and efficient services for the prevention and treatment of drug abuse and HIV.

Marsha F. Lopez, Ph.D., M.H.S., Division of Epidemiology, Services, and Prevention Research


Mechanism for Time-Sensitive Drug Abuse Research

Posted May 2021

Background

This initiative responds to the need for rapid responses to emerging policy changes and phenomena that affect the delivery and/or effectiveness of prevention and treatment services related to addiction care (in particular prescription drug use), HIV care, and the criminal justice setting. The concept provides a mechanism for accelerated review and award to support opportunities for this type of initial feasibility and pilot research, given a standard NIH grant review timeline would not allow for execution of the scientific aims.

Goal

This initiative will support pilot, feasibility or exploratory research in 7 priority areas in substance use epidemiology, prevention, and health services, including: 1) responses to sudden and severe emerging drug issues (e.g. the ability to look into a large and sudden spike in opioid or synthetic cannabinoid use/overdoses in a particular community); 2) responses to emerging marijuana trends and topics related to the shifting policy landscape; 3) responses to unexpected and time-sensitive prescription drug abuse research opportunities (e.g., new state or local efforts); 4) responses to unexpected and time-sensitive medical system issues (e.g. opportunities to understand addiction services in the evolving health care system); 5) responses to unexpected and time-sensitive criminal or juvenile justice opportunities (e.g. new system and/or structural level changes) that relate to drug abuse and access and provision of health care service; 6) partnerships between researchers and state or local organizations to support the evaluation of new local policies, programs, or practices in response to public health emergencies (e.g., the opioid crisis); 7) research collecting and examining data on the risks and outcomes associated with substance use and COVID-19 infection in the general population and among underserved populations, such as racial, ethnic and gender minorities, individuals with low socioeconomic status, and those who are incarcerated or homeless. It should be clear that the knowledge gained from the proposed study is time-sensitive and that an expedited rapid review and funding are required in order for the scientific question to be answered (i.e. an imminent policy change will not allow for standard review and funding timeline).

Marsha F. Lopez, Ph.D., M.H.S., Division of Epidemiology, Services, and Prevention Research


Social Determinants of Opioid Use: Opportunities for Community- and System-Level Interventions

Posted May 2021

Background

In September 2020, the NIH HEAL Initiative hosted a workshop, “Social Determinants of Drug Use: Establishing a Research Agenda to Inform Community- and System-Level Intervention.” Highlighting research on social determinants of health (SDOH), this meeting helped to elucidate how factors such as income/class, housing/neighborhood, race/ethnicity, immigrant status, and resources distinguish groups of people who are more or less advantaged with regard to their health status and how institutional and/or structural factors alter risk status and access to effective prevention and treatment services. SDOH often reflect systemic and community-level issues; intervening at the individual level, alone, may not lead to desired changes in the absence of intervention at the level of the environment. While programs have been implemented to address SDOH, significant gaps remain in our understanding of how SDOH impact non-medical opioid use and other substance use.

Goal

This initiative would solicit research projects that leverage existing programs that target identified social determinants (e.g., housing, employment) and study the effects of adding psychosocial and/or behavioral interventions in order to more directly address mechanisms related to opioid misuse and related outcomes. Existing programs could be implemented by state, local, or private entities and could include strategies such as expansion of mental health or social services, access to or improvements in affordable housing, access to or improvements in educational and recreational services, wage increases, or strengthening employment opportunities. The research would study impacts on non-medical opioid use (including community opioid overdoses), other substance use (e.g., non-medical stimulant use, polysubstance use) and mental health-related variables (e.g., depressive symptomology, chronic stress, etc.). Projects would be expected to specify and study mechanistic pathways through which interventions confer their effects. The primary goal of these studies would be to test the impact of multi-level strategies that directly address SDOH, on risk for opioid use and related outcomes. Ultimately, this program of research will inform efforts to implement effective and sustainable prevention strategies.

Aria Davis Crump, Sc.D., Division of Epidemiology, Services, and Prevention Research


Implementing Comprehensive HIV Services in Syringe Service Program (SSP) Settings

Posted May 2021

Background

SSPs are named as an essential tool in the Federal Ending the HIV Epidemic Initiative. The number of SSPs has increased under HHS guidance for determinations of need based on potential HIV or Viral Hepatitis outbreaks. Modeling suggests that harm reduction services, including SSPs have had demonstrable effects on reducing new HIV case among People Who Inject Drugs (PWID). CDC supports SSPs as part of a comprehensive program of HIV prevention and is interested in seeing SSPs function as hubs for providing and/or linking a range of HIV prevention and care services. Research is needed to provide evidence-based models for SSP-based delivery of comprehensive HIV services to support CDC-funded programs, as well as other funders’ HIV services. Expansion of SSPs has led to more diverse SSP settings which create opportunities as well as challenges for this work.

Goal

Develop and test intervention models for how SSPs can support implementation of evidence-based comprehensive HIV & substance use services.

This research needs to reflect diverse SSP settings (standalone, CBO-based, health dept-based) and delivery models (freestanding, mobile, telehealth. It also needs to reflect variations in resources (urban/suburban/rural) and how services are organized (e.g., hub & spoke systems, dispersed service delivery).

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


Stimulants and HIV: Addressing Contemporary and Recurring Epidemics

Posted May 2021

Background 

The opioid epidemic has evolved into an epidemic where co-occurring stimulant use is common and the prevalence of stimulant use often has overtaken opioid use. Stimulant use makes HIV treatment and epidemic control more difficult, even in opioid-affected areas where stimulants have a continuing presence. 

There are multiple stimulant epidemics with implications for HIV prevention and care. There are enduring rural and urban stimulant epidemics, including stimulant use among gay men who have sex with men and the opioid/stimulant wave of the opioid epidemic. The use of different stimulants (e.g., cocaine or methamphetamine) vary by geography and race. In addition to stimulant use disorder, problematic/episodic use can contribute to HIV risk and poor adherence. 

We have new, but still limited tools for stimulant treatment and fewer tools for addressing non-SUD stimulant use. 

Goal 

The primary goal is to improve HIV prevention and care outcomes among stimulant users by developing and testing interventions to reduce HIV risk or improve HIV care, with particular attention to PWID (regardless of how stimulants are used) and MSM. Projects should incorporate evidence-based practices for treating stimulant use disorder or develop and test components that address problematic, episodic use of stimulants. 

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


Increasing Immediate Engagement and Retention in HIV Treatment with Substance Users

Posted May 2021

Background

Ensuring all PLWH have rapid access to care, especially in resource-limited settings, remains a key challenge to the success of HIV care/treatment efforts. Same day or other rapid treatment initiation may be available, but patients may be concerned that other needs will make treatment difficult or they may face delays related to the enrollment process for treatment support mechanisms (e.g., ADAP, Ryan White, Medicaid). Similarly, long-term retention in HIV care and sustained achievement of viral suppression can be challenging even when ARV is introduced at or close to HIV diagnosis. Existing practices such as Strengths-Based Case Management and Patient Navigation often demonstrate a lack of efficacy among people with SUD.

Persons with SUD and HIV often present clinical complexities and engagement with multiple services may be necessary; where reducing and eliminating barriers (i.e. structural or individual) to immediate linkage to care is critical to minimizing time between diagnosis and treatment and can lead to achieving Ending the Epidemic goals. Even with rapid ARV uptake, this population may need additional supports to remain continuously engaged in care.

There is a need to develop and test evidence-based interventions at the systemic, organizational, and/or provider levels that can reduce the time between diagnosis and treatment while also retaining persons with SUD in HIV and SUD care.

Goal

Improve HIV treatment and care outcomes among substance users by reducing the time between HIV diagnosis to treatment among people with SUD and promoting sustained retention in SUD+HIV care.

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


Pharmacokinetics (PK) and Pharmacodynamics (PD) of Cannabis and Cannabis-Derived Products/Substances

Posted May 2021

Background

Δ9-Tetrahydrocannanbinol (THC) is the main cannabinoid responsible for the psychotropic and addictive properties of cannabis. Given the increasing diversity of cannabis and cannabis-enriched products, inconsistency in the measurement and reporting of THC exposure has been a major limitation to compare findings among studies of cannabis use. A systematic assessment of the pharmacokinetics (PK) and exposure-response relationships to account for the heterogeneity in THC concentrations for different cannabis products using multiple routes of administration is currently lacking. A variety of factors such as, presence of other cannabinoids (e.g., CBD, Δ8-THC, THCA) and non-cannabinoid constituents (e.g., terpenes, flavonoids, adjuvants/excipients, cutting agents) in cannabis and cannabis products, the food-matrix effects, delivery systems, route of administration, history of use, genetics, etc. may significantly contribute to differences in the PK and pharmacodynamics (PD), and overall the pharmacometrics of THC. Hence a systematic PK/PD assessment using a standardized measure of THC should advance research in terms of understanding its true potency, and its adverse effects and potential medical uses, while providing greater comparability across studies.

Goal

The purpose of this funding opportunity is to support human and animal research on the pharmacokinetic (PK) and pharmacodynamic (PD) effects of Δ9-tetrahydrocannanbinol (THC) that is present in cannabis and cannabis-derived products/substances. The results obtained will be reported using a “Standard THC Unit” that is now defined as 5 milligrams of THC (5 mg THC). Investigators are free to use more or less than 5 mg THC as appropriate for their study, but results should be expressed in multiples of the standard 5 mg unit. The goal is to increase the comparability of the PK/PD effects of cannabis and cannabis-derived products/substances containing varying amounts of THC and using different methods of administration.

Kiran Vemuri, Ph.D., Division of Neuroscience and Behavior


HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose

Posted May 2021

Background

Opioid Use Disorder (OUD) is a high public health priority and Opioid Overdose (OOD) continues to be a serious national crisis and a public health problem. While there are FDA-approved medications to treat OUD and OOD, none are ideal. Moreover, the optimal treatment of OUD may require therapeutic agents that are effective at specific stages along the trajectory of OUD (e.g., chronic use, physical dependence, relapse, and overdose). Development of such medication options for addressing OUD and OOD remains a challenging and unmet medical need. Achieving this goal is critically dependent on identification and pursuit of novel targets for pharmacotherapeutic development. The NIH HEAL initiative currently supports a continuum of drug development activities ranging from lead optimization through preclinical development and clinical trials. However, there are at present no programs specifically designed to discover and validate new targets for OUD and OOD. Thus, a significant gap that exists in the discovery-development pathway is research focusing on identification, validation, and pursuit of novel targets relevant to the treatment of OUD and OOD.

Goal

The goal of this initiative is to support the discovery and identification of new pharmacological targets and compounds that may be suitable for development as treatments for OUD and OOD. Recent developments in molecular biology, target identification, and drug discovery technologies provide an unprecedented opportunity to leverage these advances toward discovering new targets and drugs for intervention for OUD and OOD. The application of these emerging technologies, as non-biased approaches, could potentially lead to identification of new targets not previously considered as targets for OUD and OOD. Innovative research using these techniques is expected to expand the spectrum of therapeutic targets of relevance to OUD, including the as yet largely unexplored target classes of interest.

Sam Ananthan, Ph.D., Division of Neuroscience and Behavior


Human Post-Mortem Brain Resources for Molecular HIV and SUD Research

Posted May 2021

Background

Many NIDA researchers are interested in performing transcriptomic, epigenomic, proteomic, spatial transcriptomic, single cell, and other molecular assays on samples from subjects with SUDs with and without HIV infection. Although some human post-mortem brain resources for HIV and SUD research exist, these resources are limited.

Goal

Establish a post-mortem brain resource of well-characterized brains relevant to both SUDs and neuroHIV. Focus would be on current and future tissue needs of NIDA investigators and would include human subjects with opioid, cocaine, methamphetamine, cannabinoid, or other exposures relevant to SUDs with and without HIV infection.

Potential Ccientific Questions That Can Be Answered

What are the transcriptomic, epigenomic, proteomic, or other molecular pathways involved in SUDs, neuroHIV or at the intersection between SUDs and neuroHIV? Once identified, can newly identified targets provide foundational knowledge to guide the development of novel treatments for SUDs and/or neuroHIV?

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


HIV, SUD and Neuropathology at Blood Brain Barrier

Posted May 2021

Background

The blood brain barrier (BBB) is a target of both the HIV virus and drugs of abuse. It is a site of entry for HIV infected monocytes and macrophages that can traverse the BBB either paracellularly or transcellularly. HIV viral proteins can also attack astrocytes and tight junctions of BBB directly and compromise its integrity, resulting in the crossing of the virus, as well as drugs, into the brain. Many drugs of abuse also cause BBB dysfunction. For example, cocaine increases permeability by decreasing trans-endothelial electrical resistance and upregulating TNF-a, resulting in barrier leakages. Morphine alters BBB homeostasis as well as permeability through pro-inflammatory cytokine activity. Nicotine disrupts BBB permeability by dysregulating tight junction protein distribution. Cannabinoids affect leukocyte movement across the BBB, and alter BBB permeability. Methamphetamine induces downregulation, fragmentation, and redistribution of major tight junction proteins, reducing endothelial barrier tightness and increased paracellular permeability. Some studies have implicated blood brain barrier leakage as the cause of methamphetamine overdose. Because BBB integrity regulates both drug and virus levels in the brain, it is critical to establish the mechanisms by which HIV infection, in combination with drugs of abuse, affect BBB function and integrity and their consequences.

Tools that have recently been developed can potentially advance our understanding of the cellular composition, activity and regulation of the BBB under the assaults of HIV and abused substances. Examples of these tools range from gene chips for functional genomics and gene regulations, calcium imaging and optogenetics for glial-neuronal activities and structural biology, single cell profiling for genetic variations and cell signaling, and many variations of advanced electron microscopy for subcellular biology. Furthermore, recent advancements in Organ-Chip technology have allowed generating BBB in vitro using human iPSC-derived brain microvascular endothelial-like cells (iBMECs), pericytes and astrocytes. Currently various types of BBB Chips have been shown to exhibit in vivo physiology, displaying selective permeability to chemicals, cellular vesicles and molecules. They can recapitulate many aspects of the complex BBB functions such as activities of carrier-mediated transporters (CMT) or receptor-mediated transport (RMT). Therefore, BBB chips may provide a valid platform to study the cellular and molecular mechanisms through which HIV attacks, infects, and traverses BBB. It may also provide a standardizable and repeatable approach to study the comorbidity of HIV toxicity and damage to BBB with the presence of abused substances.

This initiative will support innovative research that will advance our knowledge of the cellular identity, activity and function of BBB in regard to the neuropathology of HIV infection and substance abuse. Particularly of interest is how the comorbidity of HIV and abused substances synergistically dysregulate or damage BBB, and exacerbates the neuropathology.

Goal

The ultimate goal of this initiative is to advance our knowledge on the physiology and function of BBB in the context of HIV infection, the neuropathology at BBB caused by HIV and abused substances, the mechanisms by which HIV and abused substances crosse BBB, and the comorbid effects of HIV and abused substances to BBB.

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


Investigating Transposable Elements and Mobile DNA as Targets of Integration for Establishing HIV Reservoirs in the Brain

Posted May 2021

Background

Microglia host the majority of the latent HIV reservoirs in the brain. Integration of HIV into the microglial genome is thought to contribute to HIV-1-associated neurocognitive diseases (HAND) and re-emergence of active infection following drug resistance. HIV primarily integrates into open chromatin near the nuclear periphery, with bias toward introns and intergenic regions. Integration sites differ in people with chronic vs. acute infection, implying that integration sites may play important roles in the formation of HIV reservoirs. Many substances of abuse, including cocaine, methamphetamine, and several opioids exert powerful environmental insults on the epigenome in the brain that induce expression of the dark genome (e.g. transposable elements and other mobile DNA that comprise 50% of the genome), thereby globally disrupting chromatin structure. When transposable elements and mobile DNA become active in people who use drugs of abuse, they potentially provide multiple integration sites for HIV in microglia. HIV integration into these unstable regions could lead to major chromosomal rearrangements and global dysregulation of transcription, ultimately contributing to HAND and provide a mechanism by which drugs of abuse increase the probability of reactivating microglial HIV reservoirs. However, despite the role that microglia play in establishing HIV reservoirs in the brain, there is a dearth of information regarding the mechanisms of HIV integration in these cells and studies of HIV integration have been largely conducted in T-cells and other leukocytes. This concept addresses these gaps by fostering studies aimed at providing a deeper understanding of the complex interplay among HIV, mobile DNA, substances of abuse, and disease progression.

Goal

The goal of this concept is to identify: 1. Key genomic contributors (e.g. molecular, genetic and epigenetic factors) to the formation of HIV reservoirs in microglia, including the potential role that transposable elements and other mobile DNA play in HIV integration in microglia; and 2. The role that substances of abuse play in modulating HIV integration through these key genomic contributors in microglia.

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


Fentanyl and Its Analogs: Effects and Consequences For Treatment of Addiction and Overdose

Posted May 2021

Background

Centers for Disease Control data show that the mortality involving the opioid fentanyl have rapidly increased in recent years. Since 2013 heroin-linked deaths have more than doubled, while fentanyl-linked deaths have increased 10-fold. Fentanyl and its analogs (known collectively as fentanils) are now entrenched in the illicit drug supply. They are commonly found in both seized opioid and non-opioid drugs, including benzodiazepines, cocaine and methamphetamine. Their widespread presence may be associated with increased overdose risk and poorer addiction treatment outcomes.

There are important distinctions between fentanils and heroin that contribute to their increased lethality, including higher potency and physicochemical differences that increase the speed of effect onset. A poorly understood feature of intravenous fentanils use is the risk of causing chest wall rigidity (CWR). Although rare, CWR has a rapid onset and greatly shortens the time window for successful overdose reversal. The distinctions between fentanils and semisynthetic opiates like heroin may underly reports that naloxone may be less effective in reversing fentanil overdoses and/or require repeated naloxone doses.

It has also been reported that when buprenorphine is used to stabilize fentanyl-positive patients, it may precipitate opioid withdrawal. The generalizability of these observations is unclear but may indicate that the therapeutics or dosing strategies employed to stabilize fentanils users may need to be re-assessed. Furthermore, anecdotal reports have suggested in utero fentanil exposure may result in more severe and prolonged Neonatal Abstinence Syndrome (NAS) than typically induced by opiates. Buprenorphine is used to treat severe NAS, but if it indeed precipitates withdrawal in fentanyl positive neonates, the role and dosing regimen for buprenorphine in treating NAS may need to be re-considered.

Fentanils are now entrenched in the illicit drug supply and the challenges they have brought need to be carefully addressed with focused research. The purpose of this Concept is to support research about the pharmacology of fentanils, the clinical characteristics and treatment of fentanil addiction and overdose.

Goal

The goal of this Concept is to advance the knowledge and understanding of the pharmacology of fentanils and the clinical characteristics and best treatment approaches to address the fentanil addiction and overdose challenges.

Aidan Hampson, Ph.D., Division of Therapeutics and Medical Consequences


NIDA Medication Development Initiative

Posted February 2021

Background

The Anti-Drug Abuse Act of 1988 (PL 100-690) provided NIDA with an $8 M increase in its annual appropriation specifically for medication development projects. With this Congressional impetus, NIDA began its Medications Development Program. In 1992, The ADAMHA Reorganization Act (Pl 102-321) stipulated that the NIDA Medications Development Program should: 1) pursue biological and pharmacological approaches to develop medications for the treatment of heroin and cocaine addiction; 2) establish close working relationships with the pharmaceutical industry; 3) conduct studies to gain approval of new medications for addiction treatment; 4) and develop a working relationship with the FDA to assure that efficacy of compounds is expeditiously evaluated and approved. Perhaps the two most noteworthy accomplishments of the Medications Development Program have been the successful collaboration with Reckitt Benckiser (now Indivior) to develop the SL buprenorphine (Subutex) and buprenorphine/naloxone (Suboxone) products (2002 FDA approvals) and the more recent collaboration with Lightlake Therapeutics (now Opiant) to develop intranasal naloxone (Narcan nasal spray; 2015 FDA approval).

Goal

Despite past successes of the Program, the addiction treatment field still has no FDA-approved treatments for stimulant (cocaine or methamphetamine) use disorders, there are no FDA-approved treatments for stimulant overdose/intoxication, and the growing problems of cannabis use disorder and synthetic cannabinoid and THC overdose/intoxication lack FDA-approved treatments. There are also opportunities to expand our options for opioid use disorder and opioid overdose treatment, with the objective of saving more lives and improving the quality of life for OUD patients. Continuation of NIDA’s Congressionally mandated Medications Development Program in 2021 and beyond will allow NIDA to address these important goals.

David J. McCann, Ph.D., Division of Therapeutics and Medical Consequences


NIDA Abuse Liability Testing Initiative

Posted February 2021

Background

The NIDA Abuse Liability Testing Program predates all current NIDA employees, and it is not known when the program was initiated. The activities of the program likely predate the establishment of NIDA (in 1974) and may have been supported by NIMH at one time. The Controlled Substances Act of 1970 (Public Law No: 91-513) placed a large number of abused drugs under special controls, and the law also describes the process by which the Department of Health & Human Services and the Drug Enforcement Agency (DEA) should work together to review pharmacological and toxicological data and make decisions regarding the possible control of new drugs. While the law requires data review for each drug under consideration for possible scheduling, it does not address the question of who should generate the necessary data. If a new drug is a potential medication, the FDA requires the relevant pharmaceutical company to generate the data. However, in the case of a new “street drug,” the NIDA Abuse Liability Testing Program usually generates the necessary data. The DEA is responsible for either providing the newly identified street drugs to NIDA or providing funds to support their synthesis, and NIDA has had the primary responsibility for conducing the necessary in vitro and in vivo preclinical testing. Current trends in drug abuse dictate the specific compounds that require testing, and data from DEA street encounters and pathology testing guide compound prioritization. Planning for this testing is a regular topic of discussion at Inter-Agency Committee on Drug Control (ICDC) meetings, where representatives from NIDA, FDA and DEA participate as the core members. Synthetic cathinones (more commonly known as “bath salts”), synthetic cannabinoids, and fentanyl analogs have been recent priorities for testing.

Goal

The continuation of NIDA’s Abuse Liability Testing Program in 2021 and beyond will allow the Federal Government to generate essential pharmacological data to guide scheduling decisions for newly encountered “street drugs.”

David J. McCann, Ph.D., Division of Therapeutics and Medical Consequences


NIDA Drug Supply Program

Posted February 2021

Background

The NIDA Drug Supply Program (NDSP) is administered by the Division of Therapeutics and Medical Consequences (DTMC). In addition to funding research in drug abuse, addiction, prevention, and treatment, NIDA facilitates such research to accomplish its mission by providing chemicals and research probes that are either unavailable, difficult to obtain, or very expensive to buy to researchers. In addition, this program also provides analytical services and limited pharmacokinetic testing for researchers’ experimental samples.

The NDSP provides various controlled drugs, other chemical substances, and marijuana and nicotine research cigarettes for research purposes to investigators working in the area of drug abuse, drug addiction, and related disciplines at academic institutions and research laboratories both within the U. S. and elsewhere worldwide. The availability of controlled substances is regulated by the United States Drug Enforcement Administration (DEA), Department of Justice under the Controlled Substances Act (CSA), and the U.N. Convention on Psychotropic Substances. Materials in the NDSP are prepared, stored, and distributed in full compliance with all local, federal and international regulations. The controlled drugs produced and distributed within the NDSP include hallucinogens, stimulants, sedatives and hypnotics, narcotics, designer drugs, cannabinoids, marijuana, as well as many other categories of controlled substances. The NDSP also maintains an inventory of other chemical substances such as opioid peptides, radio- and mass-labeled compounds, and drug metabolites. In addition, continuous efforts are made to synthesize new compounds and add them to the inventory in response to the developing needs of the research community. The stability and purity of all such compounds are periodically monitored and maintained.

During the last 40 years, the NDSP has provided approximately 20,000 compound shipments to researchers from an inventory of ca. 2,200 batches of more than 900 individual compounds. A group of more than 2,000 investigators have received materials from the NDSP since its inception.

Goal

The continuation of NIDA’s Drug Supply Program in 2021 and beyond will allow the Federal Government to continue to provide DEA controlled and non-controlled compounds that are unavailable, difficult to obtain, or very expensive to buy to researchers. Additionally, state-of-the-art analytical services will continue to be available to researchers that would otherwise struggle to have access to similar resources.

Richard “Rik” Kline, Ph.D., Division of Therapeutics and Medical Consequences


Development of Digital Therapeutics for Substance Use Disorders

Posted February 2021

Background

Digital Therapeutics (DTx) are clinical-grade mobile, web, or other software-based platforms designed to deliver treatment for medical conditions or diseases. These therapeutic interventions do not include wellness apps or telehealth which provides remote access to a clinician. Instead, DTx can deliver new or previously developed interventions that have previously only been available for delivery through direct, face-to-face interactions with a clinician. DTx have recently been able to achieve FDA authorization and, can provide therapeutic opportunities beyond those that are available under current standard of SUD care. DTx are available 24 hours a day, whenever a patient might need support. As it is more timely than ever during the COVID-19 global pandemic, access to DTx is not affected by transportation challenges, or by when a patient might have the time available to visit a clinician. Privacy can be ensured by providing discreet and confidential care, avoiding the challenges of stigma around the potential for public exposure of receiving treatment. DTx can be highly scalable, increasing access at low cost. Over the last several years, the FDA has provided a pathway for authorization of DTx and there are already some authorized for SUD (e.g., reSET and reSET-O by Pear Therapeutics). However, more work is needed to expand on the types of treatments delivered, the technologies used for delivery, DTx that work with special populations or specific SUDS, or other aspects that can increase the safety and efficacy of SUD treatments. using DTx.

Goal

The primary goal of this initiative is to move DTx to their next step in the development process, with the ultimate goal of generating new, FDA authorized, disseminated treatments for SUDs. Investigators will be strongly encouraged to reach out to the appropriate FDA Center for Devices and Radiological Health (CDRH) office via the Pre-Submission process to discuss the proposed development pathway and clinical validation data requirements.

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


Population Assessment of Tobacco and Health (PATH) Study

Posted February 2021

Background

The Family Smoking Prevention and Tobacco Control Act (FSPTCA), signed by President Barack Obama on June 22, 2009, created the FDA Center for Tobacco Products (CTP) and granted it authority to regulate the manufacturing, marketing, and distribution of tobacco products including cigarettes, cigarette tobacco, roll-your-own tobacco, and smokeless tobacco in order to protect public health. In 2016, FDA finalized a rule, commonly referred to as “deeming”, 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. The Population Assessment of Tobacco and Health (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. This study began in 2011 and is a collaboration between the National Institutes of Health (NIH) National Institute on Drug Abuse (NIDA) and the U.S. Food and Drug Administration (FDA) Center for Tobacco Products. Wave 1 of the PATH Study began in 2013 and included collection of questionnaire and biospecimen data with annual data collections through Wave 4, which began in 2016. The study transitioned to biennial data collection starting with Wave 5 in 2018 and will continue with Wave 6 in 2021.

The PATH Study 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 never users. Participants were recruited from 156 geographical primary sampling units (PSUs) across the U.S., with each PSU consisting of a county or group of counties. The multi-wave design allows for the detailed longitudinal assessment of participants’ patterns of tobacco product use, tobacco product exposures, tobacco-related attitudes and beliefs, and tobacco-related health outcomes, and provides important information used to protect the Nation’s public health and reduce the burden of tobacco-related morbidity and mortality.

Goal

The goal of this concept is to support the continuation of the PATH Study to promote scientific understanding of tobacco-product use behaviors and related health outcomes over time and to inform FDA’s regulatory activities under the FSPTCA. Specific goals include:

  • Collect, analyze, and disseminate longitudinal behavioral data to enhance the evidence base that informs FDA's regulatory decisions under the FSPTCA
  • Collect and analyze biospecimens and disseminate biomarker data to assess changes over time in exposure to harmful and potentially harmful constituents of tobacco use
  • Collect and analyze self-reported data on existing and incident disease potentially related to tobacco use over time
  • Develop and implement formative and/or nested studies to inform emerging topics on tobacco use behaviors and related health outcomes.

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


Accelerating the Pace of Child Health Research Using Existing Data from the Adolescent Brain Cognitive DevelopmentSM (ABCD) Study

Posted February 2021

Background

The Adolescent Brain Cognitive Development (ABCD) Study is the largest longitudinal study of brain development and child health in the U.S., collecting data covering multiple assessment domains from nearly 12,000 youth across the U.S. beginning when they are 9-10 years-old and continuing for a decade.

ABCD curated data are made available to the wider scientific community for analysis annually and raw neuroimaging data are released on an ongoing basis. The third annual curated data release was published in December 2020 and contains early longitudinal data, including neuroimaging and phenotypic data on the full participant cohort. The ABCD Study® also recently made available a supplemental COVID-19 data release which consists of survey responses from ABCD families about the impact of the pandemic on their lives. The surveys were sent electronically to all ABCD participants and their parent/guardian in May, June, August, October and December of 2020, the first three of which are included in this release. Data from this release as well as Data Release 3.0 and raw neuroimaging data are available to the external scientific community via the NIMH Data Archive.

Goal

As the ABCD Study moves into its 5th year of data collection covering multiple assessment domains, the available data will continue to be a significant scientific resource. The goal of this initiative is to encourage applications proposing secondary analysis of this robust, public use dataset to increase knowledge of adolescent health and development.

Elizabeth Hoffman, Ph.D., Division of Extramural Research


Advancing Pharmacotherapeutics for Substance Use Disorders (SUD): Focus on Pre-Clinical Development

Posted February 2021

Background

There is a need for new Food and Drug Administration (FDA) approved medications for Substance Use Disorders (SUD). Currently, there are medications approved by the FDA for use as an aid to smoking cessation treatment and to treat opioid use disorder, but the options for both are still limited. Moreover, there are no FDA-approved medications for cocaine, methamphetamine, or cannabis use disorders. This initiative aims to support successfully validated novel targets or drug candidates in these unmet SUD areas for drug development. Several key requirements must be in place for a drug development project to be de-risked (e.g., in vivo safety, efficacy, human evidence for target) at each stage of preclinical development. This initiative aims to support projects that have a clearly defined target product profile (TPP) to be able to continue research and to advance into preclinical development with the ultimate goal of performing Investigational New Drug (IND)-enabling activities.

Goal

This initiative aims to support therapeutics projects with one or more of the following preclinical activities:

  • Medicinal Chemistry, hit to lead development, structure activity relationships (SAR), lead optimization, clinical candidate synthesis, scale-up, back-up compound development, active pharmaceutical ingredient (API) and drug product stability
  • Metabolite identification, characterization and profiling
  • In vitro, in vivo toxicity, safety, ADME, and efficacy testing
  • Drug formulation, pharmacokinetics/pharmacodynamics (PK/PD) studies, biomarker development
  • Bioanalytical and analytical method development, validation, and testing
  • Preclinical regulatory support

Ram Arudchandran, Ph.D. and Christopher Conrad, Ph.D., Office of Translational Initiatives and Program Innovations


NIDA Animal Genomics Program

Posted February 2021

Background

There are strong heritable components to the array of phenotypes and endophenotypes associated with addictive behaviors and substance use disorders, with human genome-wide studies identifying single nucleotide variants associated with several of these phenotypes. Alleles influencing addiction-related phenotypes and endophenotypes can be identified in a wide array of model organisms, including non-human primates, rats, mice, zebrafish, flies, and worms. The alleles, genes, and genetic/biochemical pathways identified through animal model studies can be reflected in human genome-wide studies, providing an opportunity to elucidate the genetic architecture of these behaviors on a systems level, while simultaneously facilitating studies that can identify measurable aspects of the genetics, epigenetics, physiology and brain function that influence behaviors associated with substance use disorders not possible to conduct in humans.

New sequencing and data analysis tools are available for analysis of repetitive DNA, transposable elements, structural variants, indels, and other types of mobile DNA. These understudied regions of the genome are often identified through human genome-wide studies, and animal models provide a robust avenue to elucidate their role in behaviors associated with substance use disorders.

In addition to being used as a method to discover alleles, genes, and gene networks associated with addictive behaviors, model organism studies can be designed to tease out the relationships among variants and environmental components of substance use disorders, including substance of abuse, genetic background, gene x gene (GxG; epistasis), gene x environment (GxE), gene x drug (GxD), and other tractable environmental factors, that are not as easily accomplished in human genetic studies. These strong model systems capture the cellular context, identify tissue and cell-specific hallmarks, delineate relevant circuitry, help to understand longitudinal measures, and test hypotheses generated by human genetic studies. In addition, they facilitate a systems approach and can be used to develop new methods to integrate various levels of data (e.g. genomics, epigenomics, transcriptomics, behavioral, environmental), delineate epistatic, GxE, and GxD interactions at the organismal, tissue, circuit and cellular levels.

Goals

The goals of this concept are to discover allelic variants, genomic alterations, and functional changes associated with addictive behaviors in non-human animals through systems studies that employ genetic and genomics approaches that: 1. Incorporate strategies that focus on identifying and characterizing the genetic architecture of these behaviors and phenotypes, including those designed to probe mobile DNA and structural variants; 2. Integrate data across species; and 3. Delineate and test gene networks, epistatic relationships, GxE interactions, GxD associations and the influence of genetic background and other environmental influences on these phenotypes.

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


Imaging – Science Track Award for Research Transition (I/START)

Posted February 2021

Background

There is an ongoing need for a variety of scientific approaches within brain imaging research on substance use disorders (SUD). Such variety can be found -- in part -- in the form of newly independent investigators equipped with state-of-the-art imaging training and established investigators looking to leverage the insights of brain imaging within their research programs. This concept is a continuation of the currently established I/START program designed to facilitate the entry of these investigators to the area of SUD brain imaging research. The cost of obtaining preliminary data using brain imaging methods that can be used in humans (e.g., PET and MRI scans) often serves as a significant barrier to research, particularly for translational efforts. To wit, this concept encourages the entry of investigators to the area of brain imaging via the conduct of small "proof of concept" studies that can be carried out in a short period of time with limited resources and can be subsequently used as pilot data for the transition to more extensive research applications.

To date, this program has been successful, resulting in 77 unique applications and a 23% funding rate (2016-present). Further, funded I/START applicants have gone on to submit more than 25 R01 applications and 22 R21 applications to NIDA, suggesting that the mechanism has been successful in seeding further applications from a pool of new brain imaging investigators.

Goal

The goal of this concept is to seed the human brain imaging pipeline for NIDA-relevant research by facilitating new and established investigators to incorporate brain imaging tools into their research programs. Proposed studies should have the potential to add significantly to our knowledge of the substance use trajectory, including SUD, specifically on the underlying neurobiological, behavioral, and social mechanisms involved.

John R. Fedota, Ph.D., Division of Neuroscience and Behavior


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


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


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., HIV Research Program (HRP)


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., HIV Research Program (HRP)


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 


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 


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., HIV Research Program (HRP)


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