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.
- NIDA Research Education Program for Clinical Researchers and Clinicians
- National Addiction & HIV Data Archive Program (NAHDAP)
- American Indian and Alaska Native Collective Research Effort to Enhance Wellness (AI/AN CREW): Addressing Opioid/Drug Misuse, Mental Health and Pain
- Ending the Epidemic: New Models of Integrated HIV/AIDS, Addiction, and Primary Care Services
- Engaging Survivors of Sexual Violence and Trafficking in HIV and Substance Use Disorder Services
- Addressing HIV in Highest Risk Sexual and Gender Minorities
- Cohort Studies of HIV/AIDS and Substance Use
- Research to Address SUD in the Criminal-Legal System
- HEAL Initiative: Research to Increase Implementation of Substance Use Preventive Services
- Resource Networks to Advance the Impact of Addiction Services Research Through Researcher/Decision Maker Collaborations
- Development of Clinical Outcome Assessments as New FDA-Qualified Drug Development Tools for Opioid and Stimulant Use Disorders to Accelerate Therapeutic Development
- Mechanistic Studies on the Effects of Psychosocial Stress in Complex Morbidity Involving SUD/s, Psychiatric Disorders, and HIV
- Effects of HIV and Substance Use Comorbidity on the Placenta
- Interplay of Autophagy Regulated Cell Death and HIV Pathogenesis in Substance Use Disorders
- Targeting Inflammasomes in Substance Use and HIV
- Research on the Neuro-Immune Axis in the Context of HIV and Substance Use
- Chemical Probes and Drugs for Modulating HIV Transcription in People with Substance Use Disorders
- Microglial Pathophysiology in Comorbid HIV and SUD
- SCORCH (Single Cell Opioid Responses in the Context of HIV) Program: Data Coordination, Analysis, and Scientific Outreach
- SCORCH (Single Cell Opioid Responses in the Context of HIV) Program: Data Mining and Functional Validation
- ABCD Study® Data Sharing Platform
- Patient Engagement Resource Centers
- Leveraging Inpatient Medical or Surgical Hospitalizations to Improve Outcomes for People Who Use Drugs
- Rural Community-Centered Prevention and Harm Reduction Research—Responding to the Fourth Wave Opioid/Psychostimulant Epidemic and its HIV/HCV Consequences in the U.S.
- Using Cost‐Effective Technology to Develop Accessible and Affordable Products to Reduce (or Even Eliminate) Disparities in Substance Use Disorder (SUD) Diagnosis and Treatment
- Marijuana Farm and Analytics to Support the Availability of Consistent, High-Quality Material to Facilitate Cannabis Research
- Exploratory Clinical Neuroscience Research on Substance Use Disorders
- Translating Socioenvironmental Influences on Neurocognitive Development and Addiction Risk (TransSINDA)
- Mechanistic Research on Neuromodulation for SUD Treatment
- Advancing Psychedelics Research for Treating Addiction
- Remote Assessment 1: Identifying and Addressing Barriers to Participant Engagement
- Remote Assessment 2: Validation and Expansion of Remote Assessments of SUD‐Relevant Behaviors
- NIDA International Program
- Leading Addiction, Diversity, and Discovery in Education and Research (LADDER)
- Actionable Data to Inform Research‐Driven Decisions (HEAL Initiative Data2Action)
- NIDA Abuse Liability Testing Initiative
- NIDA Drug Supply Program
NIDA Research Education Program for Clinical Researchers and Clinicians
Posted February 2023
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).
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
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.
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
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.
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
Ending the Epidemic: New Models of Integrated HIV/AIDS, Addiction, and Primary Care Services
Posted February 2023
HIV/AIDS, substance use disorders, mental health conditions, and other health conditions are all highly comorbid. Currently, these services are often delivered in multiple care settings, resulting in fragmented, uncoordinated care, which contributes to suboptimal treatment outcomes. The initiative would support the development of new models of care that function as one-stop-shops capable of integrating comprehensive services, including (but not limited to) HIV/AIDS services, addiction prevention and treatment services, and primary care services.
The goal of this initiative is to develop and test replicable, scalable organizational and systems level interventions to determine how best to provide comprehensive, integrated interventions to improve the health outcomes related to HIV and SUD.
Applications would be required to utilize implementation science informed approaches, with an emphasis on scalability, replicability, quality measurement, sustainability, and cost-effectiveness. Specifically, this initiative would support: (1) care models that integrate HIV screening, prevention, and engagement in care in substance use or primary care settings; or (2) care models that integrate substance use screening, prevention, and treatment in Ryan White Clinics or other HIV Services settings, including prevention-oriented settings such as STI clinics. Applicants will be strongly encouraged to develop care models that provide comprehensive supports across the full prevention to treatment continuum for both HIV/AIDS and substance use supports. For substance use, this means care models that include screening, prevention services, and referral to pharmacotherapies as appropriate (e.g., all three FDA-approved MOUDs). For HIV/AIDS, this means treatment models should include screening, PrEP, and HAART. In response to the increased interest across HHS in addressing Hepatitis, applicants would be permitted to incorporate Hepatitis B and C screening, Hepatitis B vaccination, and Hepatitis C treatment in their models, as well.
This effort will be associated with the Ending the AIDS Epidemic by 2030 initiative; therefore priority will be given to (and not restricted to) the 48 highest burden counties, the District of Columbia, San Juan (PR) and the seven states with the highest rural HIV burden, as identified in the EHE plan. If applicants are considering geographical areas not identified as demonstrating high HIV burden, epidemiological data from 2018 or later demonstrating elevated community-level HIV risk must be provided for each geographic area involved in the proposed study. CDC, state, or local sources may be cited. Applications with international research settings should include only LMICs with appropriate HIV epidemic density, as described by UNAIDS estimates. Additionally, applications with international research settings would be required to incorporate how the proposed work addresses the country’s national plans and coordination with PEPFAR and Global Fund, where they are involved in funding services, and clearly describe relevance to the United States. Applicants would need to also explicitly identify how to sustain effective models upon the conclusion of the research study.
Minnjuan W. Flournoy Floyd, PhD, Division of Epidemiology, Services, and Prevention Research
Engaging Survivors of Sexual Violence and Trafficking in HIV and Substance Use Disorder Services
Posted February 2023
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.
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
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.
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
Cohort Studies of HIV/AIDS and Substance Use
Posted February 2023
Longitudinal cohorts of at-risk individuals can provide crucial information about transmission and acute or early phases of infection. NIDA has been supporting HIV/AIDS cohorts involving people who use substances for many years. These longitudinal cohorts provide a continuous source of data with the ability to collect information on new and emerging epidemics, infections or other public health problems or issues (new drugs or drug behaviors, co-morbidities, uptake of screening, prevention, or new treatments). Cohorts can help us identify, and quickly work to fill gaps that are identified.
The existing cohorts are well placed and able to collect data on changing dynamics in substance use such as the uptake of stimulants among opioid users and have been able to address emergent infectious diseases (COVID outbreaks), emergent drug use epidemics or other public health crises.
The purpose of this concept is to support the continuation of NIDA’s HIV cohort program to continue addressing new emerging and/or high priority research on multidisciplinary aspects of HIV/AIDS and substance use in alignment with NIH-HIV research priorities. These cohorts are prospective, observational studies in “real world settings” that include key populations at risk for HIV acquisition. Current cohorts include people who inject drugs (PWID), men who have sex with men (MSM), people living with HIV (PLWH) and this open competition would enable consideration of other populations as well.
The concept will be designed to better inform system-level or multi-level HIV and SUD interventions to increase prevention, testing, diagnosis, and treatment, as well as inform implementation research in both substance use and HIV prevention, screening, treatment, and medical care. Applicants must demonstrate the capacity to be responsive to changes to drug use and HIV epidemics, such as new drug or drug use patterns; emergent co-morbidities including emergent infectious diseases such as mpox; or changes in policies, HIV or SUD treatments, prevention strategies, and co-morbidities. Besides informing decision makers, findings should demonstrably lead to development of new, high impact intervention and epidemiology research. In addition, sites will have to demonstrate their ability to continue collection of common data elements and biospecimens to expand the data repository.
Sheba K. Dunston, EdD, MPH, Division of Epidemiology, Services, and Prevention Research
Research to Address SUD in the Criminal-Legal System
Posted February 2023
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.
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
HEAL Initiative: Research to Increase Implementation of Substance Use Preventive Services
Posted February 2023
The importance of prevention in combatting the opioid crisis is clear – identifying and implementing effective strategies to prevent the onset of opioid misuse and use disorder has the potential to yield positive individual, societal, and financial benefits. In 2020, 9.5 million people aged 12 or older misused opioids in the past year (NSDUH, 2021), suggesting that there are millions of people whose trajectories could have been changed, had they been exposed to an effective prevention strategy.
Current studies funded through the HEAL Preventing Opioid Use Disorder Program are testing whether existing interventions shown to prevent or treat non-opioid substance use disorders might generalize to opioids. However, there remain many gaps in knowledge about how to deploy prevention services. Often effective strategies are not adopted, implemented, or scaled-up, limiting their reach and impact. There is a critical need for research to develop innovative strategies to build infrastructure and capacity for implementing and sustaining prevention services that are affordable, practical, and designed in partnership with end-users.
This initiative will be part of the HEAL Preventing Opioid Use Disorder Research Program, and address existing gaps by encouraging research to identify effective strategies to disseminate and implement prevention services, and support the creation and strengthening of a prevention infrastructure. One area of interest includes the testing of innovative strategies to build infrastructure and capacity to deliver prevention services for diverse populations, particularly working in close partnership with justice and healthcare systems. This initiative could also examine scientific solutions to prevention workforce capacity challenges, including developing and testing new approaches to training and retaining a prevention workforce, identifying opportunities to integrate prevention service delivery into a variety of staff positions, and strategies to build centralized, community-based prevention systems. Other areas of interest include: (a) developing and testing of innovative strategies and models for optimizing key implementation processes, (b) research to leverage technology to facilitate access to preventive care, and (c) studies of strategies to impact organizational structure, climate, and culture, to increase the implementation of evidence-based prevention services.
Amy Goldstein, 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
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.
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
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.
The goal is to support research by the FOA 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
Mechanistic Studies on the Effects of Psychosocial Stress in Complex Morbidity Involving SUD/s, Psychiatric Disorders, and HIV
Posted February 2023
Exposure to psychosocial stressors is associated with a higher likelihood of developing psychiatric disorders and substance use disorders (SUDs). Moreover, history of psychosocial stress and SUD each contribute to higher risk of acquiring and transmitting HIV, and in people living with HIV, is associated with more severe cognitive dysfunction, reduced compliance and efficacy of anti-retroviral treatments (ART), and overall poorer functional outcomes. The mechanisms contributing to these effects operate at multiple levels, including neurocognitive and neurobiological levels. For example, chronic social stress, as well as history of neuropsychiatric disease or chronic use of drugs such as psychostimulants, lead to changes in neuroimmune function, including function of microglia, the cells that harbor HIV in brain. While associations between psychosocial stress and SUD/s, psychiatric disorders, and HIV-related CNS pathology are well-recognized, the mechanisms that may mediate these relationships remain largely unknown.
The goal of this concept is to support human-subjects and animal model research aiming to elucidate the neurocognitive and neurobiological mechanisms that underlie the associations between psychosocial stress and SUD/s, psychiatric disorders and HIV-related CNS pathology. The research supported under this concept would also include studies addressing how key neurobehavioral processes interact with substance use, HIV expression and/or actions of ART, in the context of environmental and social stressors, to impact neurocognitive and neuroimmune function in people living with HIV.
Holly Moore, PhD and Sunila Nair, PhD, Division of Neuroscience and Behavior
Effects of HIV and Substance Use Comorbidity on the Placenta
Posted February 2023
Human immunodeficiency virus (HIV) infection is widely prevalent in individuals in the reproductive age group. Globally, an estimated 1.3 million people living with HIV (PWH) become pregnant each year (UNAIDS data, 2019). With the advent of antiretroviral therapy (ART), significant progress has been made in the prevention of vertical transmission of HIV. However, although ART has clear benefits in preventing vertical transmission, ART regimens are associated with higher rates of preterm birth, stillbirth, and early infant death. Optimal development and functioning of the placenta are key factors in maintenance of pregnancy and positively corelate with maternal and fetal outcomes. Despite this, there is considerable paucity of data on the impact of HIV/ART exposure on the placenta. Even less is known on the impact of HIV/ART exposure on the placenta in pregnant individuals with substance use/misuse.
This concept is targeted at understanding the effects of HIV and/or ART on the growth, development, and functioning of the placenta in pregnant individuals with substance use/misuse, the underlying mechanisms, and the impact of placental abnormalities on maternal, fetal and/or neonatal outcomes.
Sunila Nair, PhD, Division of Neuroscience and Behavior
Interplay of Autophagy Regulated Cell Death and HIV Pathogenesis in Substance Use Disorders
Posted February 2023
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 FOAs 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.
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
Targeting Inflammasomes in Substance Use and HIV
Posted February 2023
The purpose of this concept is to encourage research to explore mechanisms of inflammasome activation, humoral immune reaction and potential antibody-mediated enhancement, and their link to immune functions in people with HIV and substance use disorders (SUDs). This concept supports studies to either (1) elucidate the mechanisms of inflammasomes in virus and drug-induced immune activation, or (2) identify molecular markers and CNS immune cells associated with HIV-1 infection or disease progression among individuals with SUD. Success of these projects may lead to development of novel therapies that target inflammasome activation or suppression to treat neuroinflammation and immune dysregulation in people with HIV.
The concept proposes to investigate the underlying mechanisms and CNS consequences of myeloid cell-triggered inflammasome activation in the context of comorbid HIV-1 infection and acute or chronic substance use. Research areas that are pertinent to this concept include, but are not limited to:
- Identify and characterize common and specific inflammasome pathways within the CNS activated by addictive drugs and HIV-1 infection
- Differential expression of inflammasomes and the structural and functional consequences of inflammasome activation in different anatomical brain regions under the influence of SUD and HIV-1 infection
- Differential expression and activation of inflammasomes in CNS cells - including resident myeloid cells (such as microglia and perivascular macrophages), astrocytes, oligodendrocytes and neurons - in the presence of addictive drugs and HIV-1 infection
- Impact of addictive substances and HIV on myeloid cell mediated inflammation in CNS
- Heterogenous inflammasome signatures in CNS myeloid cells and their use as biomarkers of neuroinflammation in people using addictive substances and living with HIV
- Role of inflammasomes in humoral and cellular immune responses against HIV in people with substance use history
- Mechanistic studies of myeloid cell-mediated inflammasome activation and its impact on cognition and behavior
- Identify and develop pharmacological approaches that regulate initial inflammasome activation in the context of SUD and HIV-1 infection
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
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.
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
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.
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
Microglial Pathophysiology in Comorbid HIV and SUD
Posted February 2023
Substance use disorders (SUD) are a common comorbidity in people with HIV and the co-occurrence of SUD and HIV results in cognitive-behavioral and neuro-pathologies that are distinct from either condition encountered alone. The disruption of neural circuits and region-specific inflammation in brain regions known to play roles in SUD (e.g. basal ganglia, frontal cortex) have been described as shared factors, but the mechanisms underlying these region- and circuit-specific effects produced by SUD in the context of HIV need investigating. Microglia represent a potential link, as they are the principal CNS reservoir for HIV, and even latent viral infection impacts cellular protein dynamics and disrupts signaling processes. Microglia are also involved in the establishment and progression of substance use disorders through activities such as synaptic pruning, metabolic regulation, and neuromodulatory signaling which impact both neuronal and nonneuronal cellular functions. The interactions of HIV infection and drug-induced alterations in microglial neuroimmune interactions with neurons and other CNS-resident cells are likely key contributors to HIV/SUD pathology. The diversity of signaling pathways and neuroanatomical circuits involved in the complex interactions of substance use and HIV makes it challenging to isolate and validate discrete causal mechanisms and key circuit components. Focusing on impacts to microglial protein expression and linking those changes to alterations in microglial functions in the context of HIV and SUD will provide a novel pathway towards therapeutic interventions that target the mutual exacerbation of these conditions.
The goal of this research initiative is to generate brain region and cell-type specific microglial protein profiles in the context of HIV and SUD. It is known that HIV co-occurring with SUD produces brain region and cell-type specific functional effects, and that microglia are a crucial lynchpin in the complex comorbidity of both conditions. The mechanisms underlying those region and cell-type specific effects and the role of microglia in their manifestation is a significant knowledge gap. This knowledge deficit can be addressed by profiling microglial protein expression and posttranslational modifications in discrete brain regions in the context of each condition alone and when presented together. These data will then inform mechanistic studies of how the identified disruptions in microglial protein expression and regulation are contributing to neural circuit dysfunctions and what key processes are viable intervention targets. These studies could be performed on human and NHP CNS tissues, and in rodent models where sufficient cellular complexity and regional architecture are present to capture the critical elements of altered microglial signaling and function. Ultimately this research will yield foundational knowledge that may inform the development of a future HIV cure and therapies for patients with and without SUD.
Tristan McClure-Begley, PhD and Anne Tsai, PhD, Integrative Neuroscience Branch, Division of Neuroscience and Behavior
Kathleen Borgmann, PhD, Da-Yu Wu, PhD, Jonathan Pollack, PhD, Genetics, Epigenetics and Development Branch, Division of Neuroscience and Behavior
SCORCH (Single Cell Opioid Responses in the Context of HIV) Program: Data Coordination, Analysis, and Scientific Outreach
Posted February 2023
The NIDA-funded SCORCH Program currently supports one data center and twelve projects generating single cell transcriptomic and epigenomic data sets from +/- HIV-infected, +/- substance use disorder (or drug exposed) human, non-human primate, and rodent brain regions. Drugs include opioids, cocaine, methamphetamine, or polysubstance. https://nida.nih.gov/about-nida/organization/divisions/division-neuroscience-behavior-dnb/basic-research-hiv-substance-use-disorder/scorch-program
This renewal would support a SCORCH data center to:
- Ingest additional data sets from SCORCH data generation projects
- Link the molecular data with appropriate metadata including clinical metadata from the National NeuroHIV Tissue Consortium (NNTC) and other post-mortem brain banks and sources
- Incorporate new data types from other NIDA projects investigating HIV/SUD effects on brain function using assays such as spatial transcriptomics, neuronal circuit analyses, or functional readouts
- Process SCORCH data sets using standardized data pipelines and perform initial data analyses
- Make the SCORCH data sets FAIR (Findable, Accessible, Interoperable, and Reusable) and available to the scientific community for data mining to identify candidates for SUD or HIV therapeutic targets
- Archive the SCORCH single cell data sets in appropriate NIH-supported archives
John Satterlee, PhD, Division of Neurobiology and Behavior
SCORCH (Single Cell Opioid Responses in the Context of HIV) Program: Data Mining and Functional Validation
Posted February 2023
The NIDA-funded SCORCH Program currently supports one data center and twelve projects generating single cell transcriptomic and epigenomic data sets from +/- HIV-infected, +/- substance use disorder (or drug exposed) human, non-human primate, and rodent brain regions. Drugs include opioids, cocaine, methamphetamine, or polysubstance. https://nida.nih.gov/about-nida/organization/divisions/division-neuroscience-behavior-dnb/basic-research-hiv-substance-use-disorder/scorch-program The consortium is currently working to enable sharing of the data generated with the scientific community.
The purpose of this initiative would be to:
- Support mining of SCORCH data to identify cell types, transcripts, enhancers, or transcriptional networks that play a role in HIV/ART or SUD molecular responses
- Support functional validation studies (e.g. epigenomic or transcriptomic manipulation, high throughput secondary screening, etc.) to confirm or deny a biological role for data-mined cell types, transcripts, enhancers, or transcriptional networks in HIV/ART or SUD molecular responses
- Provide foundational knowledge for understanding SUD and/or HIV/ART molecular mechanisms and to generate validated targets that could serve as a foundation for new SUD or HIV therapeutics (including NeuroHIV cognitive phenotypes)
John Satterlee, PhD, Division of Neurobiology and Behavior
ABCD Study® Data Sharing Platform
Posted February 2023
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.
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
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.
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
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.
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
Rural Community-Centered Prevention and Harm Reduction Research—Responding to the Fourth Wave Opioid/Psychostimulant Epidemic and its HIV/HCV Consequences in the U.S.
Posted September 2022
Data suggest that we have entered a fourth wave of the opioid epidemic, notable for the combination of opioids and stimulant misuse and continuing increases in overdose. There also is increasing recognition of mental illness as a co-occurring condition. It is estimated that only 12.7% of individuals with co-occurring mental illness and SUD receive services for both. Individuals who live in rural areas face unique challenges to accessing services such as greater stigma, fewer providers, more reliance on publicly funded services, and longer travel distance to service settings, with gaps in Wi-Fi coverage limiting the reach of telehealth. The COVID pandemic has made it more difficult to receive treatment, prevention, and harm reduction services to reduce drug misuse and contain the spread of infectious diseases such as HIV and HCV.
In 2017, NIDA launched the Rural Opioid Initiative to inform community responses to promote comprehensive, integrated approaches to prevent HIV and hepatitis C virus (HCV) infection among people who inject drugs in rural US communities. The proposed concept would build upon the success of this effort, testing interventions to improve substance use and infectious disease outcomes across the continuum of prevention and care, including health promotion, primary prevention, harm reduction, treatment, and recovery. This concept capitalizes on prevention approaches that are not specific to a single substance. Projects supported through this effort would propose intervention strategies to address more than one point on a continuum of prevention and care, including strategies to intervene early to interrupt the progression from substance use to SUD. Studies should test relevant theories of behavior change in the context of offering scalable interventions based on evidence-based practices to respond to the fourth wave of the opioid epidemic. As with the first rural opioid initiative projects, this initiative will test strategies tailored to local communities, with attention to changing drug use trends, available health services, financing capabilities, and stigma in the context of receiving services. Ultimately, the goal is to provide communities with packages of interventions that could be executed in response to community needs – be that a need to prevent new cases of OUD, stimulant use disorder, HIV, and HCV while providing high-quality harm reduction, treatment, and recovery services to individuals in rural areas who have opioid or other substance use disorders.
Aria Crump, Sc.D., Division of Epidemiology, Services, and Prevention Research,
Using Cost‐Effective Technology to Develop Accessible and Affordable Products to Reduce (or Even Eliminate) Disparities in Substance Use Disorder (SUD) Diagnosis and Treatment
Posted September 2022
More than 100,000 deaths from overdose were reported from April 2020 to April 2021 alone, continuing the upward trend from the previous decade. To stem the tide of deaths, there is a need to expand the current model of diagnosis and treatment.
Research suggests that 75% of the patients who receive treatment eventually recover and lead healthy normal life. Furthermore, it has been shown that long-term treatment significantly lowers rates of illicit drug use. Therefore, increasing the availability of treatment may help saving lives.
Currently, there are often significant barriers to receiving any treatment, which include geographical location, cost and stigma. In states with low population density, access to treatment can be hindered by the distance to treatment facility, especially in rural areas. Furthermore, the full cost of treatment (intervention services, patient care, tests, etc.) currently vary between $15k and $27k. Often, these numbers are deterrent to lead many individuals to not enter treatment as they think they cannot afford it. Stigma can also prevent a person from seeking help.
Therefore, there is a significant unmet need for better access to SUD diagnosis and treatment, together with the ability to quickly initiate and sustain it at the point of need. Many patients experience significant hurdles in finding appropriate treatment options, commuting for required appointments, getting the prescriptions filled, receiving sufficiently long treatment and staying in remission after recovery. The problem is that there is a paucity of field-deployed, cost-effective point-of-care technologies (POCT) that encompass the patient journey through SUD. Of specific interest would be technologies for use in low resource settings (e.g., community treatment centers in poor neighborhoods, jails, rural communities) that enable initiation and/or continuity of treatments. The availability of such technologies will allow to bring the treatment to the patient, and not the patient to the treatment.
This concept seeks to bring POC technologies SUD treatment in lower resource settings to commercialization. Specifically, the applications may address:
- Cost-effective POCT devices and approaches for diagnostics and treatment,
- POCT methods and devices that support therapeutic regiment while reducing the stigma from the treatment (technology that anonymizes the patient to everybody but the physician, eases access to prescription with exposing it to community, etc.)
- Cost-effective POCT devices for physiological monitoring during the treatment and recovery.
- POCT technologies that increase access to treatment in poor and rural communities, correctional facilities, as well as in tribal areas.
- POCT devices for non-pharmacological treatment and/or sustained abstinence (TMS, US, VR, etc.)
Yordan Kostov, Ph.D., Office of Translational Initiatives and Program Innovations (OTIPI)
Marijuana Farm and Analytics to Support the Availability of Consistent, High-Quality Material to Facilitate Cannabis Research
Posted September 2022
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.
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
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.
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
Translating Socioenvironmental Influences on Neurocognitive Development and Addiction Risk (TransSINDA)
Posted September 2022
There is a substantial body of evidence regarding the impacts of the social environment - defined as one’s social network and its interaction with the physical environment - on brain and cognitive development. As recent examples, prospective longitudinal studies such as HBCD and ABCD are integrating approaches informed by public health, developmental cognitive psychology, and neuroscience to examine the impact of socioenvironmental factors on brain development in the context of risk for SUD and its comorbidities.
Currently, there exists a gap in how socioenvironmental factors influencing SUD risk are incorporated into animal model research relevant to SUD. Multiple factors contribute to this gap, including a relative paucity of longitudinal non-human studies and computational models of early social environment in neurocognitive development and SUD risk phenotypes in adolescence and/or adulthood. A consortium of animal model research programs utilizing common research design elements and contributing data to a collaboratively designed and coordinated data archive would be foundational to supporting data-driven, translational computational approaches that will allow animal model findings to inform and be informed by human studies such as ABCD and HBCD.
The goal of this concept is to create pathways to support a coordinated animal research program aimed at addressing the overarching question: What are the mechanisms mediating the impact of the social environment during early life on neurobehavioral development and the emergence of SUD risk-relevant behaviors? This program would support longitudinal research in animal models to discover and test causal mechanisms. Supported projects would be required to incorporate
- Research questions informed by the human developmental research examining the impact of social environmental factors on neurocognitive development and SUD risk.
- Animal model paradigms (e.g., from developmental psychobiology) that have been validated as mechanistic models of specific psychosocial or socioenvironmental factors impacting neurobehavioral development.
- Research designs that incorporate 1) developmentally appropriate. precisely timed socioenvironmental and neurobiological manipulations, 2) longitudinal readouts of neurocognitive function and 3) adolescent/adult neurobehavioral phenotypes relevant to SUD risk.
Programs supported under this concept will leverage established paradigms for modeling early-life socioenvironmental factors and SUD-relevant neurocognitive phenotypes, and for which the “toolbox” for cell-specific and temporally precise manipulations of neural circuits is rapidly expanding. The supported programs will also address development of strategies and tools for optimal throughput of data collection and analysis, as well as tools for computational modeling using these data.
Holly Moore, Ph.D., and Janani Prabhakar, Ph.D., Division of Neuroscience and Behavior
Mechanistic Research on Neuromodulation for SUD Treatment
Posted September 2022
Given the marked heterogeneity in the etiology, pathophysiology and trajectory of substance use disorders (SUD), a toolbox of therapies will be required to mitigate this crisis. In addition to pharmacological, immunological and behavioral therapies, neuromodulation is gaining new interest, particularly given its efficacy in treating disorders that are often comorbid with SUD, such as depression. Mechanistically guided use of neuromodulation promises to be a new avenue for SUD treatment. Current research on neuromodulation for SUD treatment has been based on knowledge gained from clinical trials and has been limited to specific preselected cortical targets (i.e. DLPFC/OFC) with little understanding of the mechanism of therapeutic effect. The goal of this RFA is to identify mechanisms by which neuromodulation influences a broader set of cortical targets and related cognitive constructs relevant to SUD treatment. It promises to identify and validate new neuromodulation targets outside of the clinical trials framework and to provide a more complete understanding of the behavioral and neurobiological effects of stimulation to new identified targets, leading to stronger mechanistic understanding of SUD and its treatment
In addition to providing direct insight into the causal mechanisms of SUD, the proposed concept would inform subsequent clinical trial design via the identification of both new treatment-relevant targets and selection of more proximal metrics of efficacy in subsequent clinical trials.
Further, a funding opportunity more directly focused on the mechanistic effects of neuromodulation will engage researchers without the background or necessary infrastructure to undertake a full-scale clinical trial.
John Fedota, Ph.D., Division of Neuroscience and Behavior
Advancing Psychedelics Research for Treating Addiction
Posted September 2022
Recent clinical studies with ketamine, 3, 4-methylenedioxy-N-methamphetamine (MDMA) and classical psychedelics such as lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), ibogaine, mescaline and psilocybin have provided evidence regarding their therapeutic potential for treating psychiatric disorders. Moreover, observational data and preliminary studies have shown that these compounds induce persistent reductions in cannabis, opioid, and stimulant use thus indicating their potential for treating substance use disorders (SUD). Psychedelics have long been known to modulate the classical neurotransmitter systems while affecting neural, sensory, emotional, and cognitive function. Convergent evidence suggests that their therapeutic potential results from their ability to promote structural and functional synaptic plasticity through modulation of the function of several plasticity-related proteins. Despite such findings, there are prevailing knowledge gaps regarding their precise mechanisms of action on CNS receptors, signaling pathways, and on brain activity and connectivity, especially in the context of SUD. While certain neurobiological mechanisms underlying the physiological and pharmacological actions of psychedelics have been proposed, refinements of additional overarching experimental frameworks are necessary for advancing the field, especially to better understand the translational aspects of psychedelics, including sex differences. Moreover, across cognitive and emotional processes, more precise definitions of the specificity and duration of the post-acute effects of psychedelics are necessary to fully guide their therapeutic use. In addition to animal studies, it is necessary to replicate and extend the basic findings in mechanistic studies in humans since this will establish stronger links between the known pharmacologic effects and the relevant changes in cognitive, emotional, and social processes relevant to human SUD.
The overarching goal of this concept is to encourage research on mechanisms underlying the physiological and pharmacological actions of psychedelics. There is an emerging interest in the potential of psychedelics as therapeutics agents for neuropsychiatric disorders and for treating addiction. This concept will support basic and clinical research to address key knowledge gaps on psychedelics while encouraging collaborative efforts and multidisciplinary approaches to systematically evaluate the biological targets, mechanisms of action and other translational aspects of psychedelics including their safety, pharmacokinetics/pharmacodynamics, and efficacy, in the context of substance use disorders (SUD).
Kiran Vemuri, Ph.D., and John Fedota, Ph.D., Division of Neurosciences and Behavior
Remote Assessment 1: Identifying and Addressing Barriers to Participant Engagement
Posted September 2022
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.
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
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.
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
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).
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
Leading Addiction, Diversity, and Discovery in Education and Research (LADDER)
Posted February 2022
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.
- 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
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.
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
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.
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
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.
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