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:

Pilot Health Services and Economic Research on the Treatment of Drug, Alcohol, and Tobacco Use Disorders 

Posted September 2023

Background

NIDA’s Services Research Branch (SRB) supports rigorous research to optimize the efficient delivery of high-quality substance use treatment and related services when and where patients need them and wherever they are on the substance use disorder recovery trajectory. Research is needed to ensure that effective substance use disorder (SUD) services are delivered and sustained at scale, maximizing access to such services by the people who could benefit from them. Maximizing access includes identifying novel settings where services can be delivered and attending to the needs of vulnerable populations. Engagement with key stakeholders and patients are critical to connecting research to practice and achieving these goals.

Goal

The goal of this concept is to support pilot and preliminary health services research that will assess the feasibility, acceptability, and utility of a wide range of approaches designed to optimize the efficient delivery of high-quality substance use treatment and related services that meet the needs of individuals with SUD on the substance use disorder recovery trajectory. Relevant trials may test interventions, practices, and policies designed to optimize SUD treatment and related services accessibility, quality, effectiveness, affordability, and utilization. Relevant approaches may include both those that are novel, and those that are commonly used in practice but lack an evidence base. Investigators supported will identify hypothesis-driven research questions in the context of a broader conceptual model, which should follow through to the envisioned subsequent larger-scale services research trial. 

Keisher Highsmith Dr.PH, Division of Epidemiology, Services and Prevention Research 

Pilot and Feasibility Studies in Preparation for Substance Use Prevention Trials

Posted September 2023

Background

Pilot and feasibility studies are often warranted in advance of large, definitive clinical trials of substance use prevention interventions or large prevention services research studies. Pilot/feasibility research may be necessary to conduct activities such as finalizing intervention manuals, programs or procedures to increase the likelihood of success for a larger clinical trial. Feasibility work may include testing assessment protocols, engaging and soliciting input from practitioners, participant populations, stakeholders and end users and demonstrating the feasibility and acceptability of intervention delivery in a given system or setting. Pilot studies may be warranted when testing novel prevention interventions or innovative approaches to the delivery of an existing intervention, as it is important to determine the viability of delivering an intervention before initiating a clinical trial. With increasing attention being paid to community engaged research, a feasibility study can facilitate community partnerships to ensure that an intervention is responsive to community needs and that future clinical trial protocols are aligned with community values and will provide a rigorous test of the intervention. 

Goal

This concept aims to encourage theoretically-driven pilot and/or feasibility research in the following areas: 1) the development and pilot testing of new or adapted interventions to prevent or delay the initiation of substance use and/or the progression from use to misuse or disorder and 2) services research examining questions specific to the prevention of substance use. The latter may include pilot studies of strategies or approaches to intervention, and/or other service system-based research to address areas such as economics, funding, service quality and engagement. In addition to the prevention of substance use, misuse and disorder, other outcomes of interest for the research supported through this concept include a reduction in negative sequalae such as deaths related to impaired driving, suicidal behavior (e.g., nonfatal and fatal attempts), and substance-related acquisition or transmission of HIV infection and viral hepatitis among diverse populations and settings.

Amy Goldstein, Ph.D., Division of Epidemiology, Services and Prevention Research

Joint NIDA/NIMH Concept: Using Neuromodulation to Characterize the Continuum of Pathophysiology Between Substance Use and Mental Health Disorders

Posted May 2023

Background

Neuromodulation is a highly promising and rapidly developing treatment option for both substance use and mental health disorders (SUD and MHD), with FDA approved treatments relevant to each. However, both mechanistic studies and clinical treatment development for SUD and MHD have historically occurred relatively independently and in study populations optimized for one disorder through adoption of stringent inclusion/exclusion criteria that delineate between relevant symptom clusters. This approach fails to address the demonstrated continuum of complex pathophysiology, behavioral dysfunction, and clinical presentation spanning SUD and MHD and patently excludes a significant proportion of people suffering from these disorders.

Goal

This concept seeks applications from the SUD and MHD research communities that coordinate efforts to characterize the effects of neuromodulation on brain circuits and behaviors relevant to both SUD and MHD. To accomplish this goal, studies would specify inclusion/exclusion criteria to capture variance in both SUD and MHD symptoms. Further, studies would include measures of engagement of circuit-level targets in response to neuromodulation and dimensional measures of cognition and behavior relevant to both SUD and MHD. This research approach uses circuit dynamics to understand neurobehavioral function and to develop ecologically valid and descriptive models of the shared and discrete dysfunction across these conditions. These findings could ultimately lead to approaches for precision circuit targeting for the treatment of SUD and MHD.

John Fedota, Ph.D., and Holly Moore, Ph.D., Division of Neuroscience and Behavior, NIDA 
Lizzy Ankudowich, Ph.D., Division of Translational Research, NIMH

Mechanistic Studies on Social Behavior in Substance Use Disorder

Posted May 2023

Background

Social behavior, an umbrella term that spans multiple cognitive and emotional processes, is mediated by a complex, distributed network of brain regions. Substance use and substance use disorder (SUD) are associated with myriad differences in social processing, including but not limited to social threat processing biases and emotion recognition deficits. While substance use likely contributes to these differences, studies have identified social behavioral risk factors for SUD that predate substance use and potentially influence the substance use trajectory. There has been increasing recognition of the need to further develop research on how social behavioral processes influence the onset and trajectory of SUD. Current research gaps include:

  1. Limited data on social behavioral phenotypes that impact the SUD trajectory and, conversely, on understanding the impact of substance use on social cognition and behavior
  2. Limited understanding of social processing differences that may be specific to SUD and not manifested with substance use in the absence of SUD; for example, studies have revealed social behavioral impairments, such as impaired theory of mind processing, that may be more specifically linked with SUD and not observed with recreational or medical use.
  3. Paucity of research aimed at elucidating neural circuit mechanisms underlying social behavioral function in the context of SUD risk, particularly with respect to neurocognitive development

The above gaps can be addressed through development and application of novel behavioral paradigms aimed at assessing social cognitive function in people diagnosed with, or at risk for, SUD, and by building computational models that can leverage data from both human and animal studies. Through clinical research that leverages existing datasets (e.g., ABCD) and with original experimental studies, we can achieve mechanistic insights that incorporate the broader socioenvironmental context in our understanding of social behavior. Complementary animal models of social cognitive processes, informed by mechanistic research in humans, are also needed to address gaps in our understanding of psychosocial and neurocognitive causal mechanisms. Importantly, there is an unprecedented opportunity to advance translational research on SUD by leveraging the rapid advancement of technologies for continuous, high-resolution, holistic behavioral data from humans and animals as they interact in naturalistic settings (e.g., BRAIN Initiative Brain Behavior Quantification and Synchronization Program).

Goal

We propose to leverage ongoing momentum in these interacting fields by supporting mechanistic research in humans and animal models to advance our understanding of social processing in SUD. The proposed initiative will catalyze collaboration among experts in addiction science, social and cognitive neuroscience, cognitive psychology, sociology, neurobiology, neuroethology, intervention science, computational modeling, artificial intelligence, and lived experience with SUD to guide design and interpretation of innovative studies. Supported studies are expected to be relevant to the development of preventative and therapeutic interventions.

Topics of interest include, but are not limited to:

  • Development of novel behavioral paradigms towards investigation of SUD-relevant behavior and neural circuitry (e.g., application of machine learning approaches to quantify human behavior)
  • Application of existing behavioral paradigms (e.g., virtual reality, hyperscanning using fMRI or fNIRS, pupillometry, speech or electronic media analysis) towards uncovering social processing differences associated with SUD
  • Teasing apart differences in social behavior that predate substance use vs. those that are induced by substance use
  • Differentiating impairments in social behavior specific to SUD from those observed more broadly in recreational or medical use
  • The impact of social threat or disruptions of social bonding on social behavior in the context of SUD (e.g., biasing the animal toward choosing drug over a social interaction), and the neural mechanisms underlying these effects
  • Identification of social behavioral predictors of susceptibility to drug-seeking and/or the impact of drug use on social function using computational approaches
  • How communication of negative or positive affective states can influence drug-seeking or other SUD-relevant behavior and related brain function in the receiver
  • Neural circuit targets for increasing the sensitivity to affiliative social behavior and its impact on behavior at different stages of the SUD trajectory, e.g., slowing or preventing the transition to compulsive drug-seeking, accelerating voluntary abstinence, reducing the probability of cue- or stress-induced reinstatement of drug-seeking

Mary Kautz, Ph.D., Holly Moore, Ph.D., Vani Pariyadath, Ph.D., Division of Neuroscience and Behavior

Studying the Neuroplastic Effects of Addictive and Therapeutic Substances Using Next Generation Quantitative Readouts of Synaptic Connectivity

Posted May 2023

Background

Many, if not all psychoactive drugs affect synaptic connectivity. Both the addictive and therapeutic properties of substances have been attributed to their ability to modify neural circuitry through remodeling of synapses. However, to what extent different drugs impress unique or shared “fingerprints” on the distribution and composition of synapses, across brain regions, circuits, and cell types, remains an unresolved question. Studies that have addressed these questions in the past have often been conducted in cultured cells and have been limited in their robustness for synapse identification, and resolution scale, sampling.

Goal

This concept aims to support research to comprehensively and quantitatively map the effects of psychoactive drugs (addictive and/or psychedelic) on synapse distribution and nanostructure in intact molecularly resolved circuits. Conducting these studies with improved scale and granularity is essential to rigorously test whether synaptic connectivity encodes drug action, and how different “types” of synapses contribute to complex drug effects on physiology and behavior. The program will aim to promote the implementation of next-generation quantitative readouts of synaptic connectivity to address SUD related questions, by enabling collaborations between technology developers and addiction neuroscience experts.

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

Facilitating Translation From Epidemiology to Prevention Intervention Through “Sandpit” and “Hackathon”-like Meetings

Posted May 2023

Background

Moving science forward requires translation from one discipline to another, e.g., from bench to bedside, from research to practice. For translational work to occur effectively, there must be interdisciplinary collaboration, where investigators from different disciplines can co-design research projects to target a specific application or need. In the case of substance use research, developing and testing prevention interventions should be informed by epidemiologic investigations, and intervention research could be back translated through studies of mechanisms and long-term effects. However, the status quo for most research fields is to position research for impact within a discipline, rather than across disciplines. One way to help these multidisciplinary research teams form and start work together is through events that provide structured, hands-on activities that enable researchers to explore new ideas together. For example, “sandpits” are a meeting format that helps researchers develop their research questions, find partners who share their research interests, and support the new teams in designing future research together, while “hackathons” are a meeting format in which teams work directly with data to address a research question. Formats like these may enable concrete progress on the multidisciplinary team building that’s required for successful translational research.

Goal

The purpose of this concept is to facilitate the formation and maintenance of multidisciplinary research teams ready to employ epidemiological and/or etiological datasets and analyses to answer substance use prevention research questions and apply findings to intervention development or implementation. Projects supported through this concept will combine hands-on meeting formats, including both sandpit and hackathon approaches, with activities to sustain new research teams and networks, creating a foundational structure for research programs that have impact across disciplines.

Alexa R. Romberg, Ph.D., Division of Epidemiology, Services, and Prevention Research

Taking the First Step in Translating New SUD Research Ideas: Centers to Support Early Technical Development for Pharmacotherapeutics and Digital Therapeutics

Posted May 2023

Background

There are multiple hurdles in translating new ideas from the lab into a clinically viable commercial product. Specifically, many academic researchers are unaware of the initial steps needed to transition a discovery out of the lab and into a commercialization pathway and often do not have the resources to investigate these pathways while maintaining a productive lab. Training in the principles of defining a product, the first step in translating a promising new idea, is limited for academic researchers. Researchers with ideas for new SUD products do not understand the resources available to support early product development, leading to a loss of potential new treatments for SUD if these ideas never move beyond the lab bench.

NIDA currently supports the entrepreneurship and business development aspects of early-stage product development through the UE5 centers at MIT, Babson, and Johns Hopkins. However, more support is needed for aspects of technical development in the context of translation to enable the transition of these novel ideas into tangible biomedical products. Based on previous NIDA-supported initiatives in early translational research, addiction researchers have a strong desire to learn formal product development skills and gain access to technical expertise and support. Therefore, this concept aims to establish a center (or centers) of excellence intended to support technical needs in the emerging product development stage for early discoveries to transition them to a product development pathway. Specifically, this funding will support centers capable of technical leadership in novel pharmacotherapeutics and digital therapeutics for SUD.

Goal

Establish a technical development center (or centers) to assist researchers to develop new pharmacotherapeutics and digital therapeutics for SUD. These centers will provide idea developers with technical development support to prepare the PI for a future Phase I STTR/SBIR submission. The technical development assistance will include support from experts in “idea to product” translation activities including the following:

  • target product profile development
  • clinical need assessment
  • project plan development with timeline and milestones
  • prototype development
  • proof-of-concept study design
  • preliminary safety assessments
  • assistance in understanding current and future regulatory requirements
  • data generation to support future Phase I STTR/SBIR application

Stacie Gutowski, Ph.D., Sara Lioi, Ph.D., Tam Nguyen, Ph.D., Office of Translational Initiatives and Program Innovations

Artificial Intelligence-Enabled Translation of Interconnected Targets into New Pharmacotherapeutics for Substance Use Disorders (SUD)

Posted May 2023

Background

Drug discovery and development is a costly, high-risk, and time-consuming endeavor where the failure rate in clinical trials is 90% and are due to a lack of clinical efficacy (45%), unmanageable toxicity (30%), poor drug-like properties (15%), and lack of commercial need (10%). In recent years, drug developers have embraced artificial intelligence (AI) technologies to reduce clinical failure rates, speed drug discovery, and enable precision medicine. These AI methodologies can design new molecules and conduct virtual preclinical studies, allowing companies to refine, reduce and potentially replace in vitro and ex vivo experiments as well as in vivo studies in animals. As the COVID-19 pandemic raged, Pfizer was in a race to find a new treatment drug and relied on AI technologies to accelerate the discovery of its anti-covid drug, paxlovid. However, AI-enabled drug discovery for substance use disorders (SUD) has lagged. One main reason is that AI technologies are traditionally built around the lock-and-key mechanism that involves the identification of a drug that can target a single receptor to modulate the disease condition. Although single target-based AI drug design may be adequate for some indications, SUD can be caused by complicated mechanisms and can be outside of the traditional drug discovery paradigm. Novel AI technologies that are trained for polypharmacology could significantly improve the research and development of new medications to treat SUD. Such AI tools can assess the effects arising from binding multiple targets (beneficial polypharmacology), and thus improve potential clinical efficacy, as well as identify the pathways and mechanisms that can lead to side effects caused by drug binding to unwanted off-targets (adverse polypharmacology), and thus reduce unmanageable toxicity. Such AI tools can identify the best target combination, design effective multi-targeting agents, and inform the in vitro and in vivo assays to characterize the effects of these compounds on multiple targets and functions. To deliver proof-of-concept, there is also a need for assays utilizing more cell-free, cell-based, and animal models that can simultaneously assess the effects of compounds on multiple targets or functions. Since animal models are usually complex, costly, and time-consuming, the use of simple organisms such as C. elegans and zebrafish may be a path to proof-of-concept studies. AI trained in complex mechanisms should lead to remarkable discoveries.

Goal

Develop artificial intelligence tools and experimental assays to identify pharmacotherapeutics with desirable pharmacological properties for substance use disorders (SUD). Areas of interest include but are not limited to: 1) the development of AI tools to identify potential target combinations, design new molecules, and conduct virtual preclinical in vitro and in vivo studies to efficacy and toxicity, and polypharmacology and 2) the development of assays to determine the effects of compounds on multiple targets or functions.

Tam Nguyen, Ph.D., Office of Translational Initiatives and Program Innovations

Solutions to Enable Equitable Diagnosis and Treatment of Adverse Health Consequences for People Who Misuse Drugs

Posted May 2023

Background

As reported by SAMHSA, 61 million people used illicit drugs in 2021 alone. This number has substantially grown in the past decade, as it was 41M in 2013 and 53M in 2018. The highest prevalence of illicit use of drugs was reported among those with the highest poverty levels. People who use illicit drugs have an increased risk of adverse health consequences, including those that may be either life-threatening or involve permanent or long-term injuries. Recent data on COVID-19 showed that the pandemic had worsened these adverse health outcomes. The use of illicit drugs has been associated with a higher risk of mortality and morbidity due to overdose, mental illness, and transmissible infections, including HIV and hepatitis C viral. Endocarditis, wounds, and skin and soft tissue infections are also common complications of injection drug use. Additionally, the use of xylazine, a recent and emerging threat in the illicit drug market, is associated with severe necrotic skin ulcerations. Drug use during pregnancy has been associated with adverse maternal and child health consequences, including preterm birth and neonatal abstinence syndrome. Given their likelihood of developing diseases, people who use drugs are more likely to need diagnosis and treatment; however, they often lack equitable access to good services. Poor healthcare engagement results from socioeconomic and structural barriers directly related to drug use or its consequences (e.g., discrimination, criminalization, unstable housing, and inability to afford care). In addition, whether enacted or anticipated, self- and structural stigma mechanisms negatively affect the experience of people who use drugs in healthcare settings. Goal This concept calls for developing novel solutions targeted to improve health outcomes and reduce the impact of adverse health consequences in people who use drugs. These solutions should maximize accessibility and affordability, ideally designed to be implemented in mobile community-based care systems and able to reach the vulnerable and underserved population with limited engagement with conventional healthcare services. Solutions could include original technologies or existing technologies repurposed to target the specific needs of people who use drugs. Examples include, but are not limited to:

  • Point-of-care technologies (e.g., ultrasound, light, testing strips) for diagnosis of skin and soft tissueinfections,
  • Technologies and solutions that facilitate at-home treatment of infections (e.g., antibiotic deliverysystems for endocarditis, skin ulcer treatments),
  • Personalized, user-friendly monitoring solutions (e.g., cost-effective wearables) and interventions thatfacilitate point-of-need care while ensuring data privacy and user acceptability,
  • Technologies that facilitate the management of withdrawal symptoms for inpatient care while patientsare treated for other adverse consequences, such as wounds and infections,
  • Solutions that facilitate healthcare accessibility for people who use illicit drugs by addressingsocioeconomic barriers (e.g., unpredictable housing situations).

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

Combined Neuromodulation and Behavioral Treatment Algorithm Development for Stimulant Use Disorder (StUD) Enriched for Vulnerable Phenotype

Posted May 2023

Background

Neuromodulation technologies (e.g., TMC, tDCS, focused ultrasound, and others) are being examined across SUDs (alcohol, nicotine, opioid use disorders). However, there is a paucity of information across different patient populations, e.g., in StUD- vulnerable with cognitive dysfunction, and compulsive and impulsive traits. To neuromodulate impulsivity and to improve decision-making we propose to develop combination approaches of neuromodulation and existing and/or novel behavioral treatments, such as CBT, and mindfulness-based. Developing neuromodulation combined with behavioral treatment modalities that will help to maintain use decrease and prevent relapse would be of great value, especially in the absence of FDA-approved StUD treatments. Randomized controlled trials are needed to develop treatment algorithms.

Goal

  • Determine which brain areas for neuromodulation methods to target and for how long in terms of session duration, number of sessions, and when (timing-wise) to add the behavioral treatment follow-on
  • Characterize the functional imaging brain activity changes that would be characteristic of response and with what clinical symptoms
  • Focus on how to modulate impulsivity and enhance decision-making in the StUD vulnerable phenotype
  • Determine what could be an effective behavioral treatment paired with neuromodulation methods, especially as a remote version
  • Elucidate interactions with behavioral therapy to examine timing, extent, and cumulative effects

Tanya Ramey M.D., Ph.D., Division of Therapeutics and Medical Consequence

Psychedelic Treatment Research for Alcohol and/or Substance Use Disorder (ASUD)

Posted May 2023

Background

Psychedelic treatments are currently in clinical development for a range of mental disorders. Therapeutic areas undergoing active clinical research include alcohol and substance use disorders (ASUD). The exploration of psychedelics purported beneficial outcomes requires our urgent attention.

In a recent Workshop on psychedelics, NIDA mapped its opportunities, challenges, and gaps. Among the latter, the topics of set and setting, and whether the subjective mystical experiences are needed for the clinical effect were debated. The psychotherapeutic component of the treatment administration, the role of an expectancy and placebo effect for the total treatment effect are also important questions. Such key barriers to patients' engagement in treatment as lack of insight, and interoception impairment have a significant negative impact on all treatment options currently available.

This concept supports clinical studies applications to study psychedelic treatment administration paradigms, assess the role of psychotherapy in its administration, and describe and assess the range of clinical outcomes, including downstream functional effects, that are evidenced as the result of this treatment. The concept also invites applications that test novel endpoints and the changes that occur with the psychedelic treatment, such as insight and interoception improvements and their downstream effects on response and relapse rates.

Goal

  • To explore what psychedelic treatment administration approaches are best suitable and developed for ASUD.
  • To elucidate the role of the psychotherapy component in treatment administration and its optimal type, content, the timing of administration, and its duration.
  • Impacts of the set and setting with the current psychedelic administration paradigm and what are their key characteristics to retain.
  • The role of an insight changes and/or interoception as potential mediators/moderators of decreased substance use and relapse rate.
  • Potential novel endpoints discovery that could emerge from psychedelic treatment.

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

National Drug Abuse Treatment Clinical Trials Network - Node Infrastructure

Posted May 2023

Background

NIDA’s National Drug Abuse Treatment Clinical Trials Network (CTN) was established in 1999 to bridge the gap between research and practice to improve addiction treatment. Through the collaborative partnership of scientists and treatment providers, the CTN seeks to address critical research questions with direct relevance to clinical practice and the needs of patients. Over the last two decades, the CTN’s research infrastructure and agenda have evolved to reflect the changing landscape of the SUD treatment community, transformation of health care systems, and emerging technologies and scientific advances.

The CTN currently is comprised of 16 Nodes, a data and statistical center, and a clinical coordinating center. The CTN program is administered within NIDA through the Center for the Clinical Trials Network (CCTN). The award period for the existing CTN Nodes ends February 28, 2025.

NIDA sees value in continuing to support the CTN research infrastructure to build on the broad portfolio of research previously conducted in the CTN (https://nida.nih.gov/about-nida/organization/cctn/clinical-trials-network-ctn). Support for both new Nodes and renewals of existing Nodes can be considered. MPI collaborations to form regional consortia are especially encouraged.

Goal

The proposed initiative seeks to continue to support CTN Nodes and bolster the CTN enterprise’s capacity to accelerate the translation of science into evidence-based practices for addressing SUD that can be readily and sustainably adopted by providers and patients. This network of Nodes aims to support core scientists and clinicians with expertise and experience in leading multi-site effectiveness and implementation clinical trials; a demonstrated history of clinical or research collaboration with health systems and/or clinical research networks; and the ability to conduct timely and tailored research with the potential to influence SUD management practices and policies. Desirable features of participating Nodes include the following: 1) ability to engage diverse patients in areas highly impacted by substance use, 2) ability to develop and test interventions that address the complex challenges that patients face, including polysubstance use, co-occurring disorders, and social and environmental determinants of health and well-being, 3) ability to conduct health data science and information technology research using digital technologies and platforms such as mobile health tools and electronic health record (EHR) systems, 4) ability to conduct point-of-care research that leverages existing clinical resources and staff and evaluates pragmatic, sustainable interventions, strategies, and implementation models, and 5) ability to actively engage community partners and address research questions focusing on health equity and inclusion.

Betty Tai, Ph.D., Center for the Clinical Trials Network

National Drug Abuse Treatment Clinical Trials Network - Clinical Coordinating Center

Posted May 2023

Background

NIDA’s National Drug Abuse Treatment Clinical Trials Network (CTN) was established in 1999 to bridge the gap between research and practice to improve addiction treatment. Through the collaborative partnership of scientists and treatment providers, the CTN seeks to address critical research questions with direct relevance to clinical practice and the needs of patients. Over the last two decades, the CTN’s research infrastructure and agenda have evolved to reflect the changing landscape of the SUD treatment community, transformation of health care systems, and emerging technologies and scientific advances.

The CTN currently is comprised of 16 Nodes, a Data and Statistical Center, and a Clinical Coordinating Center (CCC). The CTN program is administered within NIDA through the Center for the Clinical Trials Network (CCTN). The award period for the existing Clinical Coordinating Center ends in summer 2024.

NIDA sees value in continuing to support the Clinical Coordinating Center to support the broad portfolio of research conducted in the CTN (https://nida.nih.gov/about-nida/organization/cctn/clinical-trials-network-ctn).

Goal

The proposed initiative seeks to provide continued support for a CTN Clinical Coordinating Center that will support and provide resources to the CTN in management and conduct of trials in substance abuse treatment research. The CTN conducts clinical trials in sites located across the nation, including studies of behavioral, pharmacological, and integrated behavioral and pharmacological treatment interventions in rigorous, clinical trials to determine efficacy, effectiveness, practicality, and feasibility across a broad range of treatment settings and diversified patient populations and to transfer research results to physicians, clinicians, providers, and patients. These studies are typically Phase III clinical trials, but can also include Phase I, Phase II, Phase IV, and/or registry trials or surveys. Desirable features of the CCC include the following: 1) ability to coordinate and support protocol development, 2) ability to review and monitor protocol implementation requirements, 3) ability to provide research and study training to research staff, 4) ability to provide study pharmaceutical services and clinical support, 5) ability to provide and coordinate drug testing and analytical laboratory services, 6) ability to support trial regulatory functions and requirements, and 7) ability to participate in and contribute to CTN committee discussion and task force initiatives.

Ron Dobbins, MBA, Program Officer, Center for the Clinical Trials Network

NIDA Research Education Program for Clinical Researchers and Clinicians

Posted February 2023

Background

The over-arching goal of this program is to support educational activities that complement and/or enhance the training of a workforce to meet the nation’s biomedical, behavioral and clinical research needs. This program is intended to support research education activities that enhance knowledge of substance abuse and addiction research for clinicians. The program is intended for those in clinically focused careers and/or those training for careers as clinicians/service providers, clinical researchers or optimally a combination of the two. This program is intended for research support only (i.e. will not support clinical training).

Goal

The overarching goals of the NIDA Research Education Program for Clinical Researchers and Clinicians  program are to: (1) train a workforce to meet the nation’s biomedical, behavioral and clinical research needs; (2) encourage individuals from diverse backgrounds, including those from groups underrepresented in the biomedical and behavioral sciences, to pursue further studies or careers in research; (3) help recruit individuals with specific specialty or disciplinary backgrounds to research careers in biomedical, behavioral and clinical sciences; and (4) foster a better understanding of biomedical, behavioral and clinical research and its implications. This funding opportunity will support creative educational activities with a primary focus on courses for skills development and research experiences. 

Aria Crump, ScD, Office of Research Training Diversity and Health Disparities

National Addiction & HIV Data Archive Program (NAHDAP)

Posted February 2023

Background

The National Addiction & HIV Data Archive Program (NAHDAP) is a National Institute on Drug Abuse (NIDA)-funded data archive program that acquires, preserves, and disseminates data relevant to drug addiction and HIV research. By preserving and making available a library of electronic data on drug addiction and HIV research in the United States, NAHDAP offers scholars the opportunity to conduct analyses of existing data on major issues of social and behavioral sciences and public policy. NAHDAP provides an end-to-end service to data depositors and data users, including but not limited to, technical assistance for data deposition and education and training support on how to use the data made available in NAHDAP. 

The establishment of NAHDAP in 2009 was based, in part, on the increasing emphasis that has been placed on the importance of data sharing in general, and specifically in the social sciences where sharing has not been standard practice. Data sharing has been increasingly encouraged or required by government and other funding agencies, including the National Institutes of Health (NIH), which will be implementing the new data management and sharing policy effective January 25, 2023. Additionally, data sharing has been identified as a necessary component of collaborations aimed at solving society’s most urgent health challenges and is integral to facilitating the development of transdisciplinary science. By establishing this archive, NIDA demonstrated the priority it places on facilitating the sharing of social and behavioral sciences data on drug addiction, including that collected by NIDA funded investigators. Since its launch in 2009, NAHDAP has made over 500 studies available to the research community. Many are HHS-supported studies, such as the Monitoring the Future (MTF) Study, Research on Pathways to Desistance, and the Population Assessment of Tobacco and Health (PATH) Study. 

Goal

The goal of this proposed concept is to support the continuation of NAHDAP to archive drug addiction scientific data and data that intersects HIV research and drug addiction, primarily in the social and behavioral science field. Specific goals include:

  • Maintain, develop, and expand NAHDAP, including the provision of all tools necessary to maintain a cutting-edge data archive focused on drug addiction, and provide technical assistance to investigators depositing data.
  • Develop a system to prioritize datasets, apply the appropriate level of curations, follow the data standards for data archive and disclosure, and implement procedures to securely protect data.
  • Facilitate sharing of archived data, including distributing data and documentation and providing data user support, technical services, and trainings to the drug addiction field. 

Janet Kuramoto-Crawford, PhD, MHS, Division of Epidemiology, Services, and Prevention Research

American Indian and Alaska Native Collective Research Effort to Enhance Wellness (AI/AN CREW): Addressing Opioid/Drug Misuse, Mental Health and Pain

Posted February 2023

Background

Through Tribal Consultations in 2018 and recently in 2022, Tribal leaders have shared that addressing the opioid public health crisis is a high priority. American Indians and Alaska Natives (AI/AN) experienced the highest rate of drug overdose death relative to other racial or ethnic groups in 2021. Despite the numerous strengths of AI/AN people, culture and communities, and the significant innovation that communities have brought to responding to the opioid crisis, health disparities for AI/ANs persist in substance use outcomes, due largely to historical trauma and long-standing structural barriers to good health. Though Tribal leaders have called for more research funding for Tribal-led research to combat the opioid crisis, there remain few funded studies in this area. Additionally, Tribal leaders have shared that available data to support response to the opioid crisis is lacking. Funding Tribes to conduct locally-prioritized research and data expansions has the potential to accelerate the development of culturally grounded, effective, and sustainable strategies to prevent or treat opioid addiction and related factors within Tribal communities, and ultimately reduce health disparities. The AI/AN CREW program is part of NIH’s Helping to End Addiction Long-term (HEAL) initiative.

Goal

The AI/AN CREW program is proposed as an innovative, agile program that can adapt as new solutions emerge in real time to accomplish goals. The program will respond to themes that emerged in Tribal Consultation, which highlighted gaps in current substance use related research, particularly on topics that require AI/AN cultural expertise and knowledge of local community conditions. These include:

  • a need for understanding the role of traditional medicine, ceremony, physical activity, spirituality, holistic conceptions of health, strength-based perspectives, and other approaches important within AI/AN communities
  • the need to invest in research that accounts for the root causes of disparities and social determinants of health (e.g., historical trauma, housing, access to high-quality health care)
  • the importance of founding NIH programs on Tribal sovereignty and relying on the principles of AI/AN research, including, when partners are needed, close partnerships and engagement.

The program will support:

  • Tribes and American Indian/Alaska Native Serving Organizations (T/ASOs) to conduct locally prioritized research to address the opioid public health crisis, including related factors
  • Expansions in research capacity and infrastructure, as identified by T/ASOs
  • Improved surveillance data to characterize factors related to opioid/drug misuse/overdose
  • Comprehensive, ongoing technical assistance to respond to capacity, infrastructure, and other needs  

Kathy Etz, PhD, Epidemiology Research Branch, Division of Epidemiology, Services and Prevention Research

Engaging Survivors of Sexual Violence and Trafficking in HIV and Substance Use Disorder Services

Posted February 2023

Background

Sex trafficking survivors are a critical, but underserved, target population for addressing the HIV epidemic. Sex trafficking, defined by the United Nations as “forced, coerced, fraudulent or deceitful entry into sex work, entry by abduction, or entry into such work as an adolescent, teenager, or young adult”, affects 4.8 million victims annually, 90% of whom are women and girls. People with SUD, migrant workers or refugees, survivors of violence or abuse, unhoused youth, and sexual or gender minorities are among the populations most at risk for sex trafficking. Sex trafficking survivors experience violence, coercion, and multiple high-risk behaviors, including sexual risk behaviors (e.g., high volume of clients, no condom use) and injection drug use, greatly increasing risk of HIV and STI infection. Additionally, a complex sequelae of behavioral health impacts may remain as they seek to cope and recover from their traumatic experiences, including substance use, PTSD, depression, and anxiety.

Sex trafficking survivors often experience challenges in engaging in the healthcare system and have an unmet need for HIV and SUD care continuum, as they have experienced many violations of trust. Trauma-informed and survivor-centered care that integrates specific education on how to identify potential “Red Flags”, awareness of stigma and biases toward sex trafficked patients, and supportive care are necessary to best engage them in the healthcare system. Innovative approaches are necessary; interventions may require targeting multiple parties (e.g., survivors, police, harm reduction organizations) to successfully deliver effective services.

Goal

The goal of this concept is to support exploratory research and preliminary interventions to address the interrelated and compounding contextual factors that contribute to substance use and HIV risk among sexual trafficking survivors. This would be accomplished through research that builds new interventions and models of care that can effectively engage ST survivors in care for SUD, HIV, trauma, and other mental health outcomes and addresses key structural and social determinants of health that contribute to risk for ST as well as barriers to and facilitators of escaping continued exploitation. 

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

Addressing HIV in Highest Risk Sexual and Gender Minorities

Posted February 2023

Background

Nearly three-fourths of new HIV cases in the US are among members of sexual and gender minorities. This proportion has increased during the past two decades, with an increasing percentage of these cases among members of ethnic/racial minorities. Existing HIV prevention and adherence interventions for sexual and gender minority populations insufficiently address substance use despite research documenting the large, identifiable attributable risk of substance use for HIV acquisition. Similarly, HIV interventions for prevention and adherence often have yielded poor results among persons with problematic levels of substance use in clinical trials. There also is accumulating evidence that substance use patterns previously not associated with HIV acquisition (e.g., cannabis) may be risk factors among sexual and gender minorities. Drug use has been evident among recent HIV outbreak clusters among men who have sex with men, but there is little recent research regarding how substance use settings and substance use networks contribute to HIV risk among sexual minorities in ways that can inform outbreak investigations.

Goal

This concept crosses prevention and care interventions, as well as epidemiologic research and will better represent sexual and gender minorities in the NIDA research portfolio. The epidemiologic focus will include drug use patterns and HIV prevalence/acquisition among sexual/gender minority persons from ethnic/racial minority backgrounds, with particular attention to stimulant use, giving consideration to syndemic production and social determinants of health and other factors that can inform novel interventions. Research related to new interventions will be expected to provide models that explicitly address substance use components to common interventions for HIV care/adherence or prevention among sexual and gender minority persons. Better models for addressing substance use in new HIV outbreaks also will be supported. In addition, modeling research will be supported that helps estimate the role of substance use in limiting the efficacy of prevention and care interventions on a population basis. Investigators will be asked to include end users of research findings as collaborators such as local or state HIV program planning activities and will include collaborations with service delivery organizations (CBOs/ASOs, health systems, FQHCs) that can implement effective interventions in their settings. 

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

Research to Address SUD in the Criminal-Legal System

Posted February 2023

Background

NIDA has a long and productive history of conducting services research to address SUD among individuals involved in the criminal-legal system. Work in the CJ-DATS, JJ-TRIALS, and JCOIN initiatives identified effective interventions to assist adults and youth transitioning between detention, community supervision, and post-release; demonstrated the value of research-practitioner partnerships; and accelerated the shift from effectiveness to implementation research. Given recent shifts in both epidemiology and public policy, new research is needed to take effective interventions to scale in jails, courts, and community corrections, and to rigorously test new and emerging models for effectively addressing the complex needs of individuals with SUD at earlier points of the sequential intercept model. 

Goal

This proposed initiative has multiple interrelated goals:

  • Support hybrid effectiveness-implementation trials on SUD services delivered at early intercept points (e.g., crisis response/911 calls; overdose response teams; police deflection programs)
  • Support implementation research with the goal of scaling up evidence-based interventions in criminal-legal systems across states or regions
  • Develop and test interventions to address stigma toward addiction, addiction treatments, and persons involved in the criminal-legal system
  • Support research on technological tools to facilitate continuity of care during transitions between community and carceral settings
  • Conduct survey, geospatial, simulation, and other modeling studies to address high priority questions for practitioners
  • Provide training and technical assistance to build the capacity of practitioners and early stage investigators to form productive research-practice partnerships
  • Translate and disseminate research findings for practitioner and lay audiences 

Tisha Wiley, PhD, Division of Epidemiology, Services and Prevention Research

Resource Networks to Advance the Impact of Addiction Services Research Through Researcher/Decision Maker Collaborations

Posted February 2023

Background

Decision makers at the state and local levels routinely make critical decisions affecting access to and the availability, cost, quality, and effectiveness of services to prevent, reduce harms from, and treat addiction and support recovery.  In most places, the scientific research enterprise does not adequately serve the needs of these decision makers, such as Public Health Commissioners, Clinical Directors of Prisons, or other leaders who allocate or manage state and federal funds. Research is neither sufficiently timely nor designed to generate the practical real-world information that could best inform decisions, or to leverage innovative approaches developed in local jurisdictions. This stymies the reach of promising advances in addiction services quality and effectiveness because they are not adequately tested in the contexts in which they will be delivered, findings are not disseminated in a way that can inform broader implementation, or because state and local decision makers need to know the potential impact in their own populations to justify allocation of resources or changes in regulations or policy.

Goal

The goal of the proposed program is to seed and propel the development of multi-jurisdictional collaborative researcher-decision maker networks where needed to advance the impact of addiction services research in advancing the quality and effectiveness of these services. These networks would ultimately be focused on the generation, dissemination, and application of research findings in real world settings.

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

Development of Clinical Outcome Assessments as New FDA-Qualified Drug Development Tools for Opioid and Stimulant Use Disorders to Accelerate Therapeutic Development

Posted February 2023

Background

To accelerate the development of new therapeutics for Opioid Use Disorder (OUD) and Stimulant (cocaine and methamphetamine) Use Disorder (StUD), there is an urgent need to create and validate clinical outcome assessments (COA) that meet the Drug Development Tool (DDT) qualification standards set by the FDA. THE Qualification of a COA via the FDA’s Qualification Program is a rigorous process in which the FDA evaluates and approves the proposed COA for a specific context of clinical trial use to expedite the development and FDA’s approval of medications. Currently, there are no FDA-qualified COAs to be used in the development of therapeutics for OUD and StUD.  At NIDA’s Division of Therapeutics and Medical Consequences (DTMC), efforts in this space include supporting the FDA-qualification of an OUD severity clinical assessment scale based on the DSM-5 criteria. The FDA accepted the Letter of Intent and the COA entered the qualification program. Another COA is being developed to evaluate opioid use craving as a patient-reported outcome and the FDA’s Advice Letter to the initial Letter of Intent was received.  Unfortunately, there are no COAs for StUD that are in the FDA-qualification pathway. Therefore, there is an urgent need to develop more COAs for OUD and start the development of COAs for StUD that enter the FDA’s DDT qualification pathway.

Goal

The goal is to support research by the funding announcement that will both expand the armamentarium of FDA-qualified COAs and open opportunities for new endpoints, as FDA-qualified DDTs. This Concept is to support the groundwork necessary to develop novel therapeutics more systematically and effectively for OUD, StUD, and overdose.

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

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

Interplay of Autophagy Regulated Cell Death and HIV Pathogenesis in Substance Use Disorders

Posted February 2023

Background

The concept aims to address the interplay of autophagy pathway and HIV infection induced cell death mechanisms under the influence of acute and chronic drug use. Autophagy is a ubiquitous mechanisms involved in the lysosomal-mediated degradation of cellular components via autophagosomes engulfing the vacuoles, one of conserved mechanisms of cellular defense against invading pathogens. Autophagic activity is inversely correlated with HIV-1 production, autophagy restricts HIV-1 infection by selectively degrading Tat in CD4+ T cells. On the other hand, exposure to substances modulates neurotransmission. While synaptic autophagy and neurotransmission are reciprocally regulated, the mode and the functional implications for this crosstalk in the context of SUD and HIV are not fully understood.

HIV proteins can directly induce cell death pathways. Additionally, HIV infection may induce T-cell apoptosis through indirect mechanisms, including pyroptosis. Pyroptosis is a pro-inflammatory form of programmed cell death that induced after abortive HIV infection on CD4+ T cells. Pyroptotic cell death is a common occurrence under inflammatory conditions and follows on from the activation of procaspase-1 via formation of the inflammasome. The innate immune responses inflammasome and autophagy regulations function like a two-way street, autophagy is as an integral immune system component, specifically, autophagy plays as a main regulator of inflammasomes. The concept of interplay of autophagy regulation on cell death and HIV in the SUD context is a coherent extension of previously issued funding opportunity that focused on inflammasome pathways, expanding our knowledge on autophagy modulated direct and/or in-direct cell death pathways would broaden the research scope of HIV innate immune responses. Understanding the innate immune responses induced by HIV and addicted substances will help identify mechanisms to develop therapeutic interventions for PWH and SUDs.

Goal

The concept focuses on the CNS cellular immune responses of substance use in HIV disease progression, with a focus on the interplay of autophagy and HIV in early infection and replication. Research questions aim to address how autophagy regulated HIV-induced cell death pathway as an approach to target HIV harboring cells in CNS of PWH and SUDs would be of interest. The concept encourages mechanistic pilot studies using in vivo and in vitro models.

Anne Tsai, PhD, Division of Neuroscience and Behavior

Research on the Neuro-Immune Axis in the Context of HIV and Substance Use

Posted February 2023

Background

Research on the modulatory effects of substances on the function of immune and neuronal cells have identified several targets and pathways of interest. Nonetheless, our understanding of the complex interactions between the immune and nervous systems, especially in the context of substance use disorders and HIV infection remains limited. The neuro-immune axes contain multiple orphan and atypical receptors and receptor-coupled systems with poorly or un-annotated endogenous and exogenous ligands and downstream effectors. The neuroinflammatory responses that accompany HIV infection and substance use include unique inflammatory processes along with changes in neuronal function at both the single cell and circuit levels. These phenomena occur via a diverse panoply of mechanisms involving the migration of HIV-infected cells across the blood–brain barrier while affecting key biological processes including neurocognitive function. Substances as single entities or as combinations (poly-substance) while having independent effects on immune function add a level of complexity to cellular and pro-inflammatory changes that are further exacerbated by HIV. Overall, the neuro-immune axes and their targetability in the context of HIV and substance use present themselves as a major opportunity for exploratory research and for basic drug discovery.

Goal

The goal of this concept is to encourage research for identifying biological targets and pathways that regulate neuroimmune interactions that are at the intersection of HIV and substance use. Research supported via this concept will help gain a fundamental understanding of transmission pathway networks and mediator and trafficking processes that are regulated by the neuro-immune axes. The concept will also encourage research towards the discovery of novel chemical entities that are effective in mitigating conditions associated with HIV and substance use, including HIV-associated neurocognitive disorder, pain, and aging.

Kiran Vemuri, PhD and Tristan McClure-Begley, PhD, Division of Neurosciences and Behavior

Chemical Probes and Drugs for Modulating HIV Transcription in People with Substance Use Disorders

Posted February 2023

Background

HIV infection and substance use are comorbid conditions that bidirectionally and synergistically influence the deleterious outcomes in people who suffer from substance use disorder (SUD).  Despite effective control of viremia by combination antiretroviral therapy (ART), people with HIV develop neurodegenerative and behavioral dysfunctions. The use of substances such as cocaine, methamphetamine, and opioids has been implicated in persistence of HIV in latent reservoirs. The persistence and transcriptional reactivation of HIV in the CNS leads to the development of neuropathological complications. While a practical cure for HIV remains elusive, strategies to address viral latency through permanently silencing HIV transcription or through activation and clearance are being intensively explored. Recent studies have revealed that a significant fraction of HIV infected cells that persist and proliferate in vivo have transcriptionally active HIV even after long term ART, and currently available antiretroviral agents do not suppress HIV transcription. HIV transcription can be inhibited by several mechanisms including epigenetic modulation, transcriptional interference and sequestration of transcription factors that regulate viral transcription. Inhibition of viral proteins such as Tat and Tar as well as inhibition of several host factors have emerged as potentially promising approaches for suppression of HIV transcription, thus providing a strong rationale for pursuing inhibition of viral transcription as a strategy to address HIV persistency and HIV-SUD comorbidity.

Goal

The goal of this initiative is to support research aimed at (1) identification of targets and pathways by which transcriptional activity of HIV can be suppressed in HIV reservoirs including the CNS in people with SUD, and (2) application of emerging small molecule drug discovery approaches to identify novel compounds that can be utilized as pharmacological probes and as drugs to suppress HIV transcription in people with HIV-SUD comorbidity.

Sam Ananthan, PhD, Division of Neuroscience and Behavior

ABCD Study® Data Sharing Platform

Posted February 2023

Background

The Adolescent Brain Cognitive DevelopmentSM (ABCD) Study is the largest longitudinal study of brain development and child health in the U.S., having enrolled nearly 12,000 youth beginning in 2016, ~98 percent of whom have been retained in the study 6 years later. The ABCD Study® has embraced an open science model where data are made publicly available to the broader scientific community on a regular basis. The ABCD Study dataset includes a wide array of data from physical, cognitive, social, emotional, environmental, and behavioral assessments, as well as multimodal neuroimaging and biospecimen collection. As a result, approximately 500 scientific papers have been published using the data to date.

As data collection has progressed, however, the amount, types, and complexity of data included in the dataset (e.g., neuroimaging, genomics, behavioral data, actigraphy data) have significantly increased. Similarly, the needs of the scientific community have evolved such that an integrated cloud-based analytic platform is critical to facilitate the use of the data by scientists from different backgrounds. The current ABCD Study data sharing platform can no longer meet these needs or scale as the ABCD dataset continues to grow. 

Goal

The ABCD Study® needs a data sharing platform that is optimized for large datasets, including neuroimaging, genomics, and other complex data, and is flexible by design so that users with different levels of analytic expertise and differing analytic requirements can accomplish what they need. The platform also must provide multiple ways to access and analyze the data – in the cloud, or on prem. Finally, it must be responsive to evolving data sharing needs in a rapidly changing landscape.

This concept proposes to advance data sharing capabilities for the ABCD Study by supporting customization of a platform with an infrastructure and databasing system well-suited to sharing neuroimaging data, and that provides data ingestion, integrated data analytics, customized user experience, and flexibility to ensure ABCD data continuity for the future, as well as a homogenous solution for harmonizing with planned data from the Healthy Brain and Child Development Study.

Elizabeth Hoffman, PhD, Division of Extramural Research

Patient Engagement Resource Centers

Posted September 2022

Background

Only 1 in 10 people who need SUD treatment ever receive it. When asked, patients and families note that available treatment options are unacceptable, undesirable, inconvenient, and inadequate to address their needs. For example, in responses to the 2020 NSDUH, individuals who met diagnostic criteria for SUD but did not receive treatment indicated the following most common reasons:  uninsured/could not afford; could not find a program that offered what they wanted; feared negative opinions of others; felt treatment wasn’t needed/could handle the problem on their own; did not have time. This NSDUH response pattern has been largely the same for two decades. Compounding these concerns are widely held perspectives (reinforced by popular media) that treatment comes in only one form: highly structured, largely institutionalized programs that are lengthy, expensive, and stigmatized. This means that efforts to implement new treatments into existing systems of care are unlikely to reduce the treatment gap. Likewise, recent efforts to integrate addiction services into general medical settings either have not permeated public awareness, or are not the solution patients are seeking.

Goal

The goal of this concept is to support the development of Patient Engagement Resource Centers that can effectively engage patients (including prospective patients, families of individuals with SUD, and persons in recovery) in meaningful dialogue to inform the design and delivery of high-quality treatment services that are responsive to their needs and preferences. Projects would take a user-centered design approach to identify and articulate patient perspectives on treatment and their desired structures and outcomes, and inform the development of new models of care that better align with these preferences. Projects would also be encouraged to test dissemination strategies to better educate the public about the full array of evidence-based treatment options available.

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

Leveraging Inpatient Medical or Surgical Hospitalizations to Improve Outcomes for People Who Use Drugs

Posted September 2022 

Background

In the United States, a relatively small number of high-need patients account for a disproportionately high level of healthcare utilization, including hospital admissions and costs. Having a substance use disorder (SUD) increases the risk of an individual falling into this high-risk, high-need population. Individuals with SUD can experience worse outcomes for their medical or surgical hospitalizations because of stigma or because their SUD may complicate the treatment in other ways (for example, poor venous access in people who inject drugs). At the same time, individuals being treated in medical or surgical wards may not receive evidence-based treatment for SUD or be linked to outpatient SUD treatment on discharge.

There are existing models for initiation of SUD treatment during general inpatient hospital stays, some of which involve linkage to care post-discharge (e.g., addiction consult services, consultation liaison psychiatry referrals, care coordinators, patient navigators, bridge clinics, etc.). Some of these have been studied formally for short time periods and/or at limited scale, with far more focus on the emergency department initiation and linkage than the inpatient components. There is literature to support the idea the hospital may be an appropriate place to screen for and assess SUDs, that SUDs may complicate or extend the hospital stay, and that initiation of treatment during hospitalization with linkage to continued outpatient care can be beneficial in reducing hospital readmissions.

Goal

The goals of this initiative are:

  • to identify the best inpatient screening, treatment initiation, and linkage models for different hospital and service systems, such as rural vs urban, large vs small hospitals, and safety net systems, including cost impacts and economic evaluations
  • to identify strategies to support the successful implementation, sustainability, and scalability of effective and cost-effective inpatient initiation and linkage interventions
  • to identify strategies to assure that patients can continue appropriate substance use disorder care after hospital discharge
  • to evaluate the impact of inpatient-to-outpatient linkage of substance use disorder care on hospital readmissions and long-term patient outcomes including morbidity, mortality, and substance use outcomes

Marcy Fitz-Randolph, DO, MPH, Division of Epidemiology, Services, and Prevention Research.

Marijuana Farm and Analytics to Support the Availability of Consistent, High-Quality Material to Facilitate Cannabis Research

Posted September 2022

Background

A contract to grow marijuana has existed since 1968, when it was under NIMH, and was established to ensure a pesticide/herbicide-free source of marijuana for scientific research.

Since the initial award, the contract site has been University of Mississippi, with Mahmoud ElSohly, becoming the project director in 1981.

The contract was the first federally legal source of cannabis for research and until recently, was the only DEA-approved manufacturer of bulk cannabis, although now there are five DEA-approved sites that can grow marijuana.

NIDA needs a continuous, standardized supply of cannabis and placebo material for research and clinical trials.  The existing contract also provides all the analytic services to determine content and purity of product produced by the Farm and from DEA and state agencies. 

Goals 

The purpose of this contract is to support the availability of consistent, high-quality material to facilitate cannabis research

  • Grow, harvest, and process cannabis plant material to produce standardized marijuana with different potencies for research.
  • Manufacture and distribute marijuana cigarettes to researchers.
  • Develop very low potency materials (almost no THC) to be used as a placebo for clinical trials.
  • Isolate and characterize different cannabis components for pharmacological studies.
  • Screen cultivars of different chemical profiles (THC, CBD and THC/CBD) for research purposes.
  • Prepare bulk quantities of specific cannabinoids (for example, THC, CBD, CBN, CBC, and CBG) as research-grade materials.
  • Ship cannabis materials to researchers throughout the U.S.
  • Follow good manufacturing practices of the US Food and Drug Administration (FDA) in preparing materials for clinical trials.
  • Initiate, maintain, and support Drug Master Files (DMF)s with the FDA.
  • Analyze confiscated cannabis products from DEA/State Agencies.

Jane B. Acri, Ph.D., Division of Therapeutics and Medical Consequences

Exploratory Clinical Neuroscience Research on Substance Use Disorders

Posted September 2022  

Background

According to The National Survey on Drug Use and Health, in 2017, approximately 19.7 million people aged 12 or older had a substance use disorder (SUD) in the past year, including 7.5 million people who had an illicit drug use disorder. Increased negative health consequences from opioid use are a leading public health problem in the US. In addition to this ongoing opioid crisis, the substance use landscape has witnessed several other recent developments: an increase in the use of psychostimulants, the growing popularity of e-cigarette consumption, and the legalization of medical and recreational marijuana. Together, these factors have renewed attention to the need for novel approaches to understanding the mechanisms underlying SUD, including clinical research studies that illuminate the neurobiological underpinnings of the disease.

Goal

This concept continues NIDA’s interest in exploratory clinical neuroscience research on SUD to support clinical research applications that are in early and conceptual stages of project development and focus on understanding the neurobiological mechanisms underlying SUD, including fundamental brain function relevant to substance use. For example, such projects could assess the feasibility of a novel area of investigation or a new experimental system that has the potential to enhance health-related research. Another example could include the unique and innovative use of an existing methodology to explore a new scientific area. These studies may involve considerable risk but may lead to a breakthrough in a particular area, or to the development of novel techniques, agents, methodologies, models, or applications that could have a major impact on a field of biomedical, behavioral, or clinical research.

Topics that would be appropriate for this concept include, but are not limited to:

  • Investigation of individual differences in neural circuitry underpinning SUD-related behavior and outcomes, including studies to understand the neurobiology underlying important risk factors for drug use and addiction
  • Testing of environmental, behavioral, or pharmacological manipulations that leverage potential treatment or prevention targets in all phases of drug taking behavior seen in the progression to development of SUDs, and identification of mechanisms of action
  • Development of computational models of network-level neural function and connectivity in the context of SUD
  • Investigation of neurobiological mechanisms related to transdiagnostic factors shared by SUD and other psychiatric disorders
  • Studies characterizing the interactions of substance use and HIV/AIDS

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

Remote Assessment 1: Identifying and Addressing Barriers to Participant Engagement

Posted September 2022

Background

While recent technological advancements have allowed for greater use of remote assessments in neuroscience research, there has yet to be universal acceptance of these assessments across broad, diverse communities. Barriers to acceptance include, but are not limited to, the technological divide between geographic regions and access to digital spaces, lack of engagement with under-resourced communities, and historic mistrust of healthcare and academic institutions. Acceptance of remote interactions facilitated by technology will help reduce geographic and social barriers to research participation and access to clinical care. Importantly, greater use of remote platforms for research and clinical purposes will provide safety to highly vulnerable participants by removing them from a hospital or high-risk or traumatized setting.

Goal

This concept proposal is designed to investigate and address barriers to help NIDA investigators find avenues to increase participant engagement and retention through remote platforms. Bringing traditionally laboratory- or clinic-based assessments to remote settings requires adequate knowledge of the sociocultural environment within which these assessments are given. As such, this concept emphasizes an interdisciplinary approach to bring together researchers, epidemiologists, statisticians, clinicians, and community collaborators to not only increase inclusion of traditionally underrepresented groups in biomedical research, but to also develop tools that are sensitive to the geographic, social, economic, and organizational components that contribute to participation barriers and SUD outcome disparities. The overarching goal is to build effective community collaboration to ensure that development and deployment of validated virtual assessments adequately serve the community.

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

Remote Assessment 2: Validation and Expansion of Remote Assessments of SUD‐Relevant Behaviors

Posted September 2022

Background

An opportunity exists to leverage the advancement, acceptance, and ubiquity of personal technology to extend the clinical research environment beyond a laboratory-based setting and deeper into a wide range of community settings that better reflect the diversity of the nation.  The COVID-19 pandemic forced the vast majority of ongoing human clinical SUD research to shift rapidly towards some degree of remote data collection.  However, it remains unclear what measures collected outside of the traditional laboratory environment yield robust, reliable data, and how such remotely collected data can be compared and combined with traditional laboratory collected data.  This concept proposes the development of validated measures for low burden home and virtual assessments of SUD relevant data (e.g. subjective clinical instruments, cognitive tasks, environmental characterizations) as well as a concentrated effort to increase the temporal resolution of this data collection.  The exponentially higher temporal resolution over extended durations possible via remote assessment coupled with the use of validated measures and other passive environmental and behavioral characterizations deepens the characterization of SUD relevant phenotypes and better characterizes the interactions between individuals and their environment. 

Goal

The robust, remote data can be employed to better model the relevant behaviors of individuals across society in the natural environment in service of the next generation of SUD interventions.  To achieve this, the current concepts seeks the validation of remote assessment measures by comparing the data collected in laboratory settings to that collected remotely and the integration of data across multiple measures/sensor types to deepen the characterization of interactions between individuals and their natural environment.

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

NIDA International Program

Posted September 2022

Background

Substance use disorders are a global health crisis requiring trained scholars and clinicians around the world. NIDA seeks to contribute to the development of international researchers to collaborate on research and to conduct related activities to facilitate international research to address the problems of drug use, abuse and addiction in the United States and abroad. In past decades, this NIDA contract has supported Hubert H Humphrey Drug Use Research Fellowship, INVEST Postdoctoral Drug Use and Addiction Research Fellowship, and the annual International Forum (in conjunction with CPDD).

Goal

The goals of this program include (1) supporting substance use disorder research, (2) training international postdoctoral or senior researchers, (3) information dissemination, and (4) international policy development.

Lindsey Friend, Ph.D., Health Science Administrator, Office of Research Training Diversity and Disparities

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

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

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

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