NIDA - National Institute on Drug Abuse Grants

NIDA - National Institute on Drug Abuse

Project Summary: The rising incidences of synthetic opioids misuse and emerging psychoactive substances pose significant challenges for public health and forensic toxicology. Conventional detection methods such as liquid chromatography-mass spectrometry (LC-MS) offer high sensitivity and specificity but are costly, require skilled operators, and are not feasible for rapid, point-of-care applications. To address these limitations, this project aims to develop a Surface-Enhanced Raman Spectroscopy (SERS)-based lateral flow assay for the rapid detection and quantification of existing and emerging illicit drugs in urine samples. This platform is designed to provide comparable analytical performance of LC-MS while reducing costs, increasing portability, and enabling drug testing in resource-limited settings such as rural health clinics, emergency departments and harm reduction centers. The proposed approach integrates three key innovations: (1) a SERS-active lateral flow cartridge that processes the urine sample – removing potential interferents while simultaneously separating drug mixtures and metabolites by Thin Layer Chromatography (TLC). Raman signals are enhanced via embedded nanoparticles in the TLC material for high-sensitivity detection. The SERS approach is a label-free technique that directly measures the unique vibrational modes of drug molecules, eliminating the need for biological elements like antibodies or aptamers. Unlike labeled methods, it has no strict shelf-life or storage requirements and can rapidly adapt to emerging drugs, for which specific biological recognition elements are unavailable; (2) a low-cost, Fourier Transform Raman (FT-Raman) instrument engineered for portability. The FT-Raman system offers several advantages over typical dispersive Raman systems: It provides higher spectral accuracy through interferometer-based calibration. Additionally, FT-Raman system uses a NIR excitation source to reduce fluorescence from biological samples. With fewer moving parts, the FT-Raman system offers more stability and requires less maintenance; (3) advanced chemometrics / machine learning algorithms for spectral analysis, enabling precise identification and quantification of drug compounds and their metabolites. Future phases will focus on prototype refinement and commercialization, targeting a per-test cost below $10 to enhance accessibility. Successful development of this technology has the potential to transform drug testing by enabling real-time, reliable, highly sensitive detection in decentralized settings, improving clinical decision- making and public health interventions.

NIDA - National Institute on Drug Abuse

Project Summary/Abstract: The basal ganglia are a group of interconnected subcortical brain nuclei that play a crucial role in motor control and decision-making and are affected in various neurodevelopmental, neurodegenerative, and psychiatric disorders, making a basic understanding of the function of this circuitry highly translationally relevant. The 2026 Basal Ganglia GRC meeting will bring together the world's leading basal ganglia researchers to discuss recent advancements and new insights into the function of basal ganglia circuits in health and disease. The five-day conference will concentrate on presenting unpublished data. The program features speakers and discussion leaders from various career stages, institutions, and subfields, with the goal of fostering interdisciplinary discussions that connect knowledge about synapses and circuits to higher-level computations. Afternoon free time and communal meals will provide opportunities for informal networking, welcoming trainees into the field and fostering lasting collaborations and friendships within our scientific community. The meeting will also incorporate an additional 1.5-day GRS organized exclusively by and for trainees. The programs for the 2026 Basal Ganglia GRC & GRS were designed to celebrate investigations of basal ganglia circuits from multiple scientific viewpoints, with contributions from innovative researchers around the world. Given that the meeting has always been held in the United States since its inception in 2014, and since previous reviews of the conference emphasized a desire for more international representation, we have moved the 2026 meeting to Italy. A deliberate effort was also made to include new speakers and topics that were not covered in previous meetings, for example with a specific session on astrocyte functions in the basal ganglia. Other topics include non-motor functions of the basal ganglia, complex neuromodulatory interactions, new technologies for investigating basal ganglia function, and new models for understanding the plasticity and function of basal ganglia circuits. As such, the overall title of “Linking Synapses, Circuits, and Computations in the Basal Ganglia” was chosen. The 2026 Basal Ganglia GRC & GRS have 3 specific aims: (1) Create a forum for the discussion of cutting-edge basic science related to basal ganglia function, inclusive of the innovative new contributions of early-career researchers, (2) Connect across multiple levels of investigation, from synapses to circuits to computations, by bringing together a wide variety of researchers from around the world, and (3) Promote collaboration and mentorship by providing a welcoming, interactive conference environment for early-career researchers. Completing these aims will advance basal ganglia research by encouraging new ideas and collaborations among researchers who might not otherwise come together and inspiring the next generation of scientists. These activities will accelerate the pace of discovery and translation to the clinic, consistent with the mission of NIH.

NIDA - National Institute on Drug Abuse

Recovery from substance use disorder (SUD) is challenging for individuals with criminal legal system (CLS) involvement, who often face resource insecurities, stigma, and damaged relationships. Involvement of loved ones is critical for recovery, providing valuable support to help individuals build and sustain recovery capital, the internal and external resources that help individuals to initiate and sustain recovery. However, loved ones may lack support, education, and resources that would help them to effectively support the recovering individual. This application responds to RFA-DA-26-024 with the overall aim of improving recovery capital for recovering persons with CLS involvement and increasing support for their loved ones through adapting and testing an innovative, dyadic intervention. By providing support to both the recovering person and their loved one, this intervention (Support Towards Addiction Recovery [STAR]) will facilitate positive connections and enhance social support – critical factors in building recovery capital and sustaining recovery efforts. Specific aims of this phased project include: R61 – Adaptation and Feasibility Testing: Aim 1: To strategically adapt coaching services for loved ones to serve dyads of recovering individuals with CLS involvement and their identified supportive loved ones for delivery in recovery community centers (RCCs). Guided by the ADAPT-ITT framework, the STAR Intervention will include one-on-one sessions with two types of coaches – a recovery coach (RC) for the recovering person and Loved One Coach for the loved one – and structured joint dyad sessions. R33 – Intervention Effectiveness and Implementation: Aim 2: To evaluate effectiveness of the adapted STAR Intervention for recovering persons and their loved ones. The R33 phase will use a hybrid type 1 effectiveness-implementation design. Dyads will be randomly assigned to receive one of the following 6-week conditions: (1) RC-Only (n=100 dyads), with weekly RC services for the recovering persons and the loved ones receive referrals to RCC services only; or (2) STAR Intervention (n=100 dyads), in which both dyad members receive weekly coaching sessions (4 individual, 2 joint) from an RC or Loved One Coach. It is expected that the STAR Intervention will lead to (1) increased recovery capital, reduced days of substance use, and reduced CLS contact for the recovering person; (2) improved psychological well-being, coping skills, and resource knowledge for the loved one; and (3) enhanced social support and connection for both dyad members. Aim 3: To examine implementation outcomes of acceptability and appropriateness as correlates of intervention outcomes, as well as obstacles and facilitators to intervention implementation, using a mixed methods approach. The implementation outcomes will be measured through participant-level surveys and qualitative interviews with participants and coaches. The STAR Project addresses a crucial research gap by focusing on both recovering individuals and the capacity of their loved ones to provide support – a critical need for CLS-involved individuals – and has the potential to make a significant impact towards enhancing scalable, sustainable services in RCCs.

NIDA - National Institute on Drug Abuse

In this R13 application we request support for the 4th Gordon Research Conference (GRC) on “Neurobiology of Drug Addiction,” taking place in May 2026 in Castelldefels, Spain. The objectives of this GRC are to foster open discussion of novel research developments, build new collaborations, and propel the next generation of both scientific advances in addiction research and addiction neuroscience researchers. To achieve these objectives, we will pursue the following four specific aims at the meeting: 1) To create an international forum that will promote deeper understanding of the neurobiology of addiction, based on groundbreaking findings from basic science, clinical, and community focused research; 2) Introduce novel and emerging research techniques to facilitate understanding of drug addiction; 3) Promote interdisciplinary interactions amongst addiction researchers, stimulating the exchange of ideas and collaborations that will advance the field of addiction research; and 4) Foster the development of the next generation of addiction researchers by facilitating and encouraging the participation of students, postdoctoral fellows, and early career investigators. The conference focuses on presentations and discussions at the frontiers of addiction research. The scope of the lectures will be confined to basic and clinical studies involving addictive drugs (including alcohol) and the nervous system and will focus on mechanisms of compulsive drug use, relapse, and vulnerability to addiction. The meeting will also break down barriers to progress by uniting investigators with synergistic and complementary expertise in areas ranging from molecular mechanisms to translational clinical research, community focused research, and addiction theory. The conference will provide a forum to address the latest developments in addiction research in an open and highly interactive GRC format, which includes formal talks interspersed with ample discussion time, poster sessions, and informal discussion periods that cultivate communication and collaborations. This conference setup differs from that of other meetings in the field and will provide a unique opportunity for close interactions among investigators at all stages of their careers and among investigators with different research approaches and cultural perspectives. Concerted efforts to support participation of students, postdoctoral fellows, early-stage investigators, and rigorous scientists from across a range of backgrounds and intellectual foundations in addiction research will nurture the growth of the next generation of addiction researchers. We will hold an accompanying Gordon Research Seminar (GRS) in 2026 immediately prior to the GRC, as we did in previous years. The GRS will provide a forum for students and postdoctoral fellows. In addition, a substantial number of GRC talks will be delivered by early career scientists. We envision that the Neurobiology of Drug Addiction GRC will continue to significantly advance our understanding of the neural mechanisms underlying drug addiction and stimulate the development of novel hypotheses, research directions, and therapeutic approaches.

NIDA - National Institute on Drug Abuse

PROJECT SUMMARY/ABSTRACT Advancements in neuroscience, including magnetic resonance imaging (MRI), have significantly improved our understanding of opioid use disorder (OUD) and brain function, yet due to the heterogeneity in the disorder and complexity of the brain, controlled comprehensive approaches in heterogeneous populations are a necessity to characterize individual variability. Here, longitudinal multi-parametric MRI is proposed to assess brain features associated with OUD in genetically heterogeneous stock rats sourced from the NIDA-funded Rat Oxycodone Biobank (U01DA051937), which provides rats with fully characterized genome and addiction-like behaviors, going through a state-of-the-art pipeline with escalation of oxycodone intake following extended access to intravenous oxycodone self-administration. Leveraging features from structural, diffusion, and functional MRI, our investigation seeks to capture the individual differences in the brain, at baseline before oxycodone exposure (Aim 1: pre-existing), and following the oxycodone extended self-administration paradigm during acute withdrawal (12 h) (Aim 2: oxycodone- induced), within the same rats that show vulnerability or resilience to developing oxycodone addiction-like behaviors. We hypothesize that there will be an interaction between the results from both aims. The I/START R03 proposal will allow for the introduction of MRI imaging into the PARC research environment, as a for the PI new, clinically relevant approach, which will complement her current preclinical work with single- cell whole-brain imaging and simplify the translation of the findings for human applications. The collaborative pilot with the Rat Oxycodone Biobank thus aims to set up the basis for larger follow-up studies that will allow for the generation of a heterogeneous, high-quality imaging dataset that will be made publicly available and complement already extensive genomic and behavioral characterization in the same animals. This data will significantly contribute to our understanding of the variable impact of opioids on the brain and individual differences in vulnerability to OUD, providing a unique opportunity to disentangle pre-existing differences from those that are a consequence of exposure to oxycodone. Ultimately, this research seeks to pave the way for improved prevention and personalized treatment strategies, thereby reducing illness and disability associated with OUD.

NIDA - National Institute on Drug Abuse

Project Summary/Abstract Opioid agonist treatment (OAT) is highly effective in preventing morbidity and mortality related to opioid use disorder (OUD), but long-term engagement is complicated by physical, social, and structural factors, especially for women. Postpartum women with OUD face the challenging transition from hospital care to the community, both for themselves and their newborns. Fear of judgment from healthcare providers may discourage women from asking for help or accessing necessary support services. The presence of supportive individuals—such as family or friends—can increase recovery capital; however, support people may require additional education and skills to effectively assist their loved ones, representing a critical gap in their ability to influence treatment outcomes. Theory-based, evidence-supported Patient Navigation (PN) interventions improve OAT engagement by addressing social, structural, and internal barriers (e.g. mistrust) using motivational techniques and providing tangible resources. This study aims to leverage the strengths of both PN and supportive family or friend involvement to enhance recovery capital and, secondarily, improve retention in community-based OAT. We hypothesize that training and engaging support persons will promote recovery capital by targeting social capital (by fostering stronger relationships), human capital (through increasing self-efficacy), and cultural capital (by promoting norms and values that support recovery). This project aligns with the objectives of RFA- DA-26-024, which emphasizes innovative strategies to improve care transitions and enhance recovery capital. The proposed study is a randomized controlled trial of a PN intervention called Supporting Treatment for Opioids and Recovery Capital (STORC) that blends PN with an added component designed to enhance recovery capital for postpartum women through additional training for chosen support persons. This intervention will provide patients with care coordination and resource referrals, and will provide support persons with comprehensive tools, including knowledge about OUD treatment, effective communication strategies, and emotional support. Patient navigation, combined with targeted training for support persons, equips family and friends with the skills and knowledge to offer more effective, impactful support for their loved ones in recovery. This project is significant to public health because it employs a recovery capital framework to explore how support persons can play a critical role in the recovery efforts of new mothers at high risk of overdose.

NIDA - National Institute on Drug Abuse

PROJECT SUMMARY The prefrontal cortex (PFC) is essential for all aspects of affect, cognition, and behavior and has established roles in all forms of mental illness, aging, development, and substance use disorders. The PFC has been studied intensely over the past four decades, although it has only been relatively recently that scientists have been able to routinely monitor neural activity in such a way as to be able to decode ongoing cognitive processes and affective responses. This highlights that PFC research is at a new and exciting point in time. With this new frontier in PFC research, a new Gordon Research Conference (GRC) on the Frontal Cortex was established in 2022 to provide a forum for researchers interested in the PFC to quickly exchange ideas. This meeting brings together researchers studying humans as well as different animal models (non-human primates, rats, mice) and a variety of experimental approaches (e.g., lesions, pharmacology, anatomy, physiology, molecular tools, computational models). The meeting has been highly successful at developing a strong community of scientists interested in discussing topics across disciplines, concepts, models, and techniques. The next GRC will convene in Holderness, NH in August 2026. It is our hope that financial support can be obtained from NIDA and NIA to build upon our successes and support the meeting. This support will allow us to offset the attendance costs of our invited speakers and trainees, especially early career investigators. We propose the following Aims: (1) To convene a multidisciplinary scientific workforce around fundamental questions in cross-topic, cross-species frontal cortex research. The conference will feature panels on aging, development, circuit function, therapeutics, affect, cognitive control, and more, in keeping with the goal of connecting disparate scientific fields whose interaction could lead to exciting research and novel therapeutic approaches. (2) To unite a multidisciplinary scientific workforce around powerful, emerging technologies in frontal cortex research. Sessions will discuss the use of powerful tools such as optogenetics, chemogenetics, calcium imaging, computational modeling, and more, and how they can be used to link studies in animal models such as mice and rats to findings from work in humans and non-human primates. (3) To promote the development of early-career researchers in frontal cortex research. In the service of this goal, we will support participation from trainees and early-career investigators, including providing financial support for attendance, and we will have the discussion leader of the last session focus on facilitating meaningful conversations among GRC attendees across all career stages to discuss barriers to career advancement and/or strategies that support professional development.

NIDA - National Institute on Drug Abuse

Substance use disorders (SUDs) are one of the most prevalent chronic behavioral health issues in the United States and are responsible for significant morbidity and mortality. However, there is a high rate of recovery from SUDs. The loved ones of those in recovery can be an important source of support. Unfortunately, relationships are often strained by the chronic relapsing and remitting nature of SUDs, and SUD-related stigma may impede support from loved ones. Efforts to implement evidence-based interventions for loved ones have been hampered by a number of factors, including required specialized training for interventionists and the lengthy nature of the interventions. Efficacious and scalable interventions are therefore needed to guide the loved ones of those in recovery in evidence-based approaches to support the recovery process. mHealth facilitated interventions could be used to address these barriers, allowing for more efficient use of interventionist time through automation while maintaining “on demand” availability and the human touch that many find helpful. We propose to refine the recovery specific content of the KulaMind Platform (KM-R), which is an AI-powered online program that aims to improve healthy family/social network behaviors and self- regulation skills of loved ones of those in recovery to strengthen the social support network. In addition to online skill building and educational modules, each loved one is matched with a coach who provides emotional support, accountability, and troubleshooting via one-on-one video sessions and “on demand” text-based support. Lastly, KM-R includes access to a community forum that allows loved ones to connect with others with shared experience. In the R61 phase, we will work with our Community Advisory Board to refine the content of KM-R; conduct an open label pilot study with 30 dyads (individual in early recovery and a loved one), in which the loved ones receive access to KM-R for 3 months, to examine the feasibility, acceptability, and preliminary signs of efficacy of the intervention; and further refine KM-R based on participant experiences. In the R33 phase, we will randomly assign 460 dyads consisting of an individual in recovery and a nominated loved one to the KM-R condition (3 months of access to KM-R for the loved one) vs. loved one referral to Nar-Anon. We will follow the dyads for 6 months. It is hypothesized that KM-R, relative to Nar-Anon referral, will result in higher recovery capital among individuals in recovery and less SUD-related stigma among loved ones (primary outcomes). In addition, in dyads assigned to KM-R vs. Nar-Anon referral, we expect better relationship satisfaction; less substance use among the individuals in recovery; and enhanced knowledge about SUDs and evidence-based treatment and greater self-efficacy to support recovery among loved ones (secondary outcomes). From study outset, we will solicit Community Advisory Board, participant, and stakeholder input regarding potential implementation challenges. This will allow us to proactively address these challenges and will enhance future clinical integration should KM-R be found efficacious.

NIDA - National Institute on Drug Abuse

Project Summary. The prevalence of daily cannabis use and cannabis use disorder (CUD) has increased in the United States over the past two decades. Unfortunately, psychosocial treatments produce minimal long- term abstinence rates and no FDA-approved medications for CUD exist. Thus, identifying novel CUD treatment targets is an increasingly urgent public health need. Stress-elicited cannabis use motivation has been implicated in worse CUD outcomes, but a mechanistic understanding of how acute stress increases cannabis use motivation in CUD is limited. The PI’s work has demonstrated that acute psychosocial stress enhancement of subsequent cannabis cue incentive salience, as indexed by the late positive potential (neural measure of approach-motivated attention recorded using electroencephalography [EEG]), was associated with worse CUD severity and intervention response, independent of subjective craving. Moreover, hypothalamic pituitary adrenal [HPA]-axis, rather than noradrenergic or subjective reactivity to the psychosocial stressor was associated with subsequent potentiation of the cannabis cue-elicited late positive potential. These studies suggest that non-genomic, rapid glucocorticoid effects may be a contributing mechanism in stress amplification of neural drug-cue reactivity, but their correlational designs preclude causal inference. Further, psychosocial stressors are unable to isolate HPA-axis vs. noradrenergic components of stress reactivity. To isolate HPA- axis activation and test causality, pharmacological manipulations, common in animal models but rare in human studies, will be used to produce separate and co-operative glucocorticoid (hydrocortisone) and noradrenergic (yohimbine) activation. We will employ a 2x2 randomized, placebo-controlled double-blind crossover design in 36 cannabis users with severe CUD. Our primary aim is to test the causal potentiating effect of glucocorticoids on neural drug-cue reactivity, and further determine if the effect depends on co-occurring noradrenergic stimulation. Preclinical work indicates that glucocorticoids can potentiate reward motivation via mobilization of endocannabinoid activity (primary target of cannabis). Thus, as an exploratory aim in line with NIDA priorities (NOT-DA-22-048), we will obtain plasma samples to test the impact of pharmacological stress on circulating endocannabinoids and their mediating role in glucocorticoid potentiation of neural drug-cue reactivity. This project represents a highly novel integration of a rigorous pharmacological challenge design with biological markers of drug-cue incentive salience and endocannabinoid system activity. If hypotheses are confirmed, one causal mechanism through which stress increases neural cannabis cue reactivity will be known, which has immediate implications for testing experimental therapeutics. The long-term goal is to understand how a stress- related mechanism predictive of worse CUD phenotype is generated and can be blocked in CUD. Development of this model will provide a valid, efficient and (relative to other neuroimaging methods) low-cost approach to screen candidate medications and optimize psychosocial drug cue exposure therapies.

NIDA - National Institute on Drug Abuse

PROJECT SUMMARY The U.S. overdose crisis remains an urgent public health concern, with recent data demonstrating an increase in fatal overdoses due to polydrug use with stimulants and opioids. People living with HIV (PLWH) are at increased risk of drug-related overdose, with studies showing that HIV seropositivity increases overdose risk. There is a gap in U.S.-based studies conducted in the past 5 years examining overdose trajectories and risk factors among PLWH during the ongoing opioid crisis. Syndemics theory posits that the co-occurrence of two or more health conditions (i.e., drug use and HIV) exacerbates the negative health effects of any or all health conditions involved. Research examining syndemic risk factors for drug overdose among PLWH has been limited to cross-sectional designs, has not measured access to overdose prevention services (e.g., naloxone, medication for opioid use disorder; MOUD), or assessed risk factors across the socio-ecological model levels. Further, there is a critical gap in examining trajectories of drug overdose risk and access to services among PLWH during the most recent wave of the opioid crisis (2019-2025), characterized by polydrug use of stimulants and opioids. This Substance Use Dissertation Research Award (R36) aims to develop a syndemics framework to identify overdose risk factors among PLWH who use drugs across the levels of the socio-ecological model (individual, social, and structural). This quantitative research study will address two research aims: (Aim 1) to examine trajectories of overdose incidents, risk, and access to overdose prevention services (e.g., naloxone, MOUD) among PLWH, and (Aim 2) to examine the influence of syndemic risk factors across the levels of the socio-ecological model on trajectories of overdose incidents, risk, and access to overdose prevention services among PLWH. Longitudinal, multilevel modelling will be used to estimate trajectories of self-reported overdose incidents, polydrug use with psychostimulants and/or opioids, naloxone availability, and MOUD access over time from 2019-2025 among PLWH in the CFAR Network of Integrated Clinical Systems (CNICS) database. Syndemic risk factors at the individual-level (Hepatitis C co-infection, depression), social-level (intimate partner violence, childhood trauma), and structural-level (housing instability, recent incarceration) will be included in the modelling to identify how syndemic factors influence overdose risk among PLWH. This dissertation grant will contribute to the applicant’s goal of an academic research career and will advance an innovative research program investigating overdose risk among PLWH through a multisystemic lens. By adopting a transdisciplinary approach and collaborating with experts in syndemics theory, multilevel modeling, and social science scholarship, this research seeks to provide novel insights into the determinants of overdose risk among PLWH who use drugs. Our ultimate goal is to develop a comprehensive syndemics framework that integrates the socioecological perspective in identifying risk factors across the individual-, social-, and structural-levels. The outcomes of this research will guide targeted interventions to reduce drug overdose among a high-risk, underserved population.

NIDA - National Institute on Drug Abuse

ABSTRACT The ongoing opioid crisis in the United States, with over 80,000 overdose deaths in 2023, disproportionately affects rural communities where access to medications for opioid use disorder (MOUD) remains limited. Natural disasters, such as hurricanes, further disrupt healthcare infrastructure, treatment continuity, and medication supply chains—exacerbating barriers to care in these underserved regions. Yet, little is known about how such disasters impact MOUD systems, especially in rural areas. This 12-month R36 study will investigate how hurricanes affect MOUD access through two complementary aims. First, a triple-difference analysis will quantify changes in buprenorphine and methadone distribution to pharmacies and treatment centers across rural and urban counties using ARCOS (Automation of Reports and Consolidated Orders System) data—a national DEA-managed database that tracks controlled substance shipments at the transaction level. Second, in-depth interviews with MOUD providers in Western North Carolina, a rural region severely affected by Hurricane Helene, will explore how providers adapted to treatment disruptions. Guided by the Healthcare Resilience Model, this multi-methods approach will assess system absorptive, adaptive, and transformative capacities in disaster contexts. Findings will provide actionable insights to strengthen rural health system resilience, inform disaster preparedness policy, and improve continuity of MOUD care during future emergencies—supporting NIDA’s priority to overcome barriers to addiction treatment.

NIDA - National Institute on Drug Abuse

PROJECT SUMMARY The 2026 Gordon Research Conference on Membrane Transport Proteins, “The Dynamic Membrane Transporter: Gateways to Health & Disease,” will convene ~200 investigators from academia, industry, and medicine at the Renaissance Tuscany Il Ciocco, June 14–19 (trainee-led GRS, June 13–14). This location facilitates participation by a broad international community of scientist, trainees, and early-career scientists working on membrane transport proteins. The broader scientific exchange directly benefits public health in the United States by speeding advances in the understanding of disease mechanisms, the development of new drugs, and the identification of promising therapeutic strategies. It also ensures that the United States researchers remain fully engaged with the discoveries, technologies, and research shaping drug discovery in this important field. Membrane transporters comprise roughly 10 % of the human genome, yet fewer than 4 % are clinically exploited, despite their central roles in prevalent disorders, including autism, depression, ADHD, addiction, and diabetes, and in rare diseases such as Christianson syndrome and mucoviscidosis. Breakthroughs in cryo-EM, AI-driven structure prediction, live-cell biosensors, and human-derived disease models now make it possible to translate fundamental transporter biology into first-in-class therapeutics, creating a timely need for a forum that seamlessly links molecular mechanisms to clinical applications. The program’s nine themed sessions and two plenary lectures deliberately pair structural and mechanistic discoveries with preclinical and clinical perspectives, covering topics from vesicular neurotransmitter loading and blood–brain-barrier gateways to ABC/OCT1-mediated drug disposition. Interwoven “Technology Spotlight” talks and “Reality-Check” panels will showcase state-of-the-art methods while candidly addressing their limitations, establishing rigorous, field-wide standards. A 1.5-day, trainee-run Gordon Research Seminar, anchored by keynote mentors Drs. Sara Jones and Walter Boron, plus mentoring innovations such as “Scientist Speed-Dating” lunches and the forum Breaking the Mold: Overcoming Barriers to Career Advancement will foster an inclusive, supportive environment that cultivates the next generation of transporter scientists. Guided by three specific aims, catalyzing translational science, elevating rigor and reproducibility, and building a global workforce, the conference is poised to reveal new transporter ligands, biomarkers, and drug-delivery strategies; to disseminate best-practice methodologies; and to launch enduring mentorship networks. By uniting siloed disciplines in a confidential, off-the-record environment that encourages presentation of unpublished data, the 2026 GRC will accelerate transporter-based solutions for some of today’s most urgent unmet medical needs.

NIDA - National Institute on Drug Abuse

Project Summary Capillary liquid chromatography (LC) using UV-absorption detection alone does not have enough sensitivity to detect trace amounts of new emerging psychoactive substances and harmful adulterant compounds, such as fentanyl and xylazine in urine samples at the required 1 ppb level without laborious and time-consuming sample preparation steps. In comparison, detection using tandem mass spectrometry (i.e., MS/MS) eliminates most of these sample preparation steps because of its exceptional sensitivity and selectivity. Unfortunately, LC-MS/MS instrumentation is large, expensive, and beyond the operating expertise of typical workers involved in treating substance use disorders. On the other hand, an analogous technique, ion mobility spectrometry (i.e., IMS), is much smaller, simpler to operate, and possesses the required high sensitivity. In this project, we propose to construct and evaluate a miniature tandem IMS detector (i.e., IMS/IMS) that can be easily mounted in the column-detector cartridge of our commercial compact, portable Axcend Focus capillary LC for trace analysis of current and emerging psychoactive substances in bodily fluids and other samples. The use of tandem IMS with field induced fragmentation introduces structural content into mobility spectra to ensure positive compound identification. We have assembled a team comprised of top scientific experts in capillary LC and miniaturized IMS to ensure successful completion of this proposed work. The success of this Phase I project will pave the way to develop and commercialize a powerful new analyzer to address trace analysis needs related to drug addiction and overdose as well as many other diverse applications.

NIDA - National Institute on Drug Abuse

PROJECT ABSTRACT Over 60% of adolescents with substance use disorders relapse within 90 days of completing treatment, largely due to fragmented data, delayed intervention, and lack of adolescent-specific clinical guidelines. This Phase I SBIR project aims to develop and validate the technical feasibility of LEVL, a novel clinical decision support (CDS) system designed specifically for early detection of relapse risk among adolescents. LEVL integrates physiological markers (heart rate, heart rate variability, sleep), behavioral data, and environmental context into an adaptive, FHIR-compliant platform that proactively alerts clinicians when elevated relapse risk is detected. The platform also features an adolescent-facing mobile application to support timely interventions and self-management. The primary goal of this Phase I study is technical feasibility, establishing the prototype’s usability, clinician adoption, and preliminary validation of the predictive risk model. Clinical predictive validity and direct clinical effectiveness in reducing relapse will be rigorously evaluated in future Phase II trials. This study will use a structured Delphi process for expert consensus on biomarkers, proprietary analytics for predictive relapse risk detection, iterative usability testing, and a 90-day feasibility trial to refine the prototype. Adolescents experiencing untreated or recurrent SUD may incur lifetime healthcare expenditures exceeding $30,000–$40,000, making early intervention a valuable cost-savings strategy. Early identification and proactive intervention have strong potential to significantly reduce healthcare costs associated with relapse. By enabling clinicians to intervene earlier through proactive alerts, LEVL aligns with federal healthcare priorities emphasizing evidence-based care, targeted cost-savings, and early intervention in substance use disorders.

NIDA - National Institute on Drug Abuse

Project Summary This STTR Phase I application brings together a company, Unchained Health, Inc., with the mission of reducing the burden of addiction, and a leading addiction researcher, Dr. Danielle Dick, Director of the Rutgers Addiction Research Center, to develop an interactive, web-based personalized prevention program for addiction for commercialization. Substance use disorders (SUDs) are among the most costly health conditions, creating a tremendous burden on affected individuals, families, and society at large. Because the development of SUD is preceded by a prolonged trajectory of risk related behavior, there should be ample opportunity to intervene early to prevent progression to problems. Based on the current research, we know who is most at risk for SUDs; however, there is no product currently available to bring this information to the public at scale. ~80% of individuals say they would want to receive personalized risk information for SUDs. This proposal would create a novel interactive program that will deliver personalized risk information, followed by tailored evidence-based recommendations and resources to reduce risk. Unchained Health, Inc. plans to bring this interactive feedback program to the public on a scale appropriate to the magnitude of the problem. It capitalizes on Dr. Dick’s 20+ years of NIH funded research on risk prediction for addiction, and how to create engaging prevention programming. Importantly, Dr. Dick’s preliminary work suggests that personalized risk information is more effective at reducing substance use than standard prevention programs. The Phase I Specific Aims focus on feasibility and commercial potential. In Phase I we will (Aim 1) Build the interactive personalized feedback program on Unchained Health, Inc. platform. The program will consist of two primary parts: (Part 1) the delivery of personalized risk estimates, and (Part 2) the provision of tailored resources to reduce risk. (Aim 2) Conduct an initial market survey to gauge interest and evaluate product price points from two primary target audiences: (1) emerging adults, who are entering a high risk period for the onset of SUDs, and (2) parents of emerging adults, who want to assist their children with avoiding problems and promoting well-being as they transition into adulthood. We will also (Aim 3) seek input from the FDA about possible regulatory requirements. Phase 1 Deliverables will be an executed licensing agreement with Rutgers, a minimum viable product, market data on interest and customer acquisition costs to guide direct-to-consumer marketing strategy, and guidance from the FDA. These activities will lay the foundation for a Phase II application, which will focus on customer feedback on the platform for program refinement, an RCT to evaluate and quantify effects on substance use and mental health associated with program engagement, and further refinement of marketing strategies. At the completion of Phases I and II, we aim to have a novel prevention program ready for commercialization, with the ultimate goal of reducing the burden of addiction and promoting healthy outcomes.

NIDA - National Institute on Drug Abuse

ABSTRACT Approximately 5.3 million individuals in the United States used cocaine in the last year and 1.4 million met the diagnostic criteria for Cocaine Use Disorder (CUD). CUD is a devastating disease with significant consequences for affected individuals, their families and society, yet there are currently no FDA-approved treatments. Recently developed methodologies in tissue clearing and cell-specific labelling allow for unbiased interrogation of brain regions that are activated in response to cocaine and other drugs. These imaging techniques can advance our understanding of neural processes that contribute to addiction by identifying functional brain networks that are perturbed in response to repeated drug exposures. Previous studies have successfully used whole-brain c-Fos mapping along with functional connectivity analysis in cleared brains to identify patterns of activity that change in response to cocaine, methamphetamine, opiates and alcohol. These studies only considered a single genetic background, however, which could limit translational significance. Only about one in five people who use cocaine will go on to develop CUD suggesting that individual differences, including genetic factors, contribute to risk. However, little is known about genetic and neural mechanisms that drive the transition from cocaine use to CUD and why some individuals are more at risk than others. Identifying brain networks that are differentially activated in response to cocaine in genetically heterogeneous mice would inform our understanding of how individual genetic differences contribute to drug response and reward. These studies will reveal interactions between drug exposure and genetic background that could uncover unique mechanisms that increase risk for CUD and lead to novel targets for prevention and treatment.

NIDA - National Institute on Drug Abuse

Project Summary Recent estimates show 85% of United States adults own a smartphone and 56.6% report using a mobile health application in the past year. Mobile health applications targeting substance use and use disorder can fill numerous treatment gaps, such as providing broader access, enhanced flexibility, and opportunity for individual self-determination. At the same time, app quality is variable, poorly understood, and both academic and commercial developers are flooding the marketplace. The proposed Phase One STTR project will establish foundation research and development for the Addiction Application Gradebook, a web platform dedicated to the description, evaluation, and market assessment of smartphone- and web-based applications for substance use disorder (SUD) information/prevention, harm reduction, treatment, and recovery. While increased availability of mobile apps for SUD is an important step forward, rapid growth coupled with the absence of an infrastructure for organizing, evaluating, and tracking these products has resulted in a large and difficult to navigate landscape. Therefore, the Phase One aims of this proposal are to conduct research and development in three key areas related to SUD app 1) Identification, 2) Evaluation, and 3) Tracking to yield a minimum viable product design that would set the stage for Phase Two development, testing, and commercialization. The proposed project outlines clear and measurable milestones for success that include a procedure for ongoing app identification, assembling an expert Delphi panel, and creating a novel SUD app evaluation framework as well as a model for understanding the SUD app innovation pipeline. The culmination of project milestones will be foundation data for a web platform with functionality for no cost public education (i.e., the public can search and find the right app for a given SUD need) and commercialization via a business-to-business membership model (i.e., app developers, employee assistance contractors, mHealth investors and scientific funders can obtain market assessments, product comparisons, and innovation trajectory analytics). The proposed project is well aligned with NIDA Strategic Priorities, particularly Areas 2 and 5 related to prevention, treatment, harm reduction, recovery, and scientific innovation translation. The Addiction Application Gradebook can fill several needs in a rapidly growing mHealth market valued at 93 billion dollars in 2023. There is currently no comparable product while there is commercial potential for the general business model we propose (i.e., app selection, market research, and analytics). Phase One is focused on building the platform scientific base; in Phase Two we will prioritize web-design, incorporation of artificial intelligence capabilities, and commercialization.

NIDA - National Institute on Drug Abuse

PROJECT ABSTRACT Non-disordered drug use (NDDU) is a severe public health concern. Stimulants like methamphetamine cause long-term damage to regions of the brain that regulate cognitive functions, psychiatric symptoms, and promote drug-seeking behavior. Methamphetamine use increases the risk of stroke and damage to white matter (WM), both of which can impact cognitive function. We have a collection of MHC class II constructs that bind to and downregulate the expression of CD74—the primary receptor for macrophage migration inhibitory factor (MIF), a key inflammatory indicator of methamphetamine use. These constructs have a therapeutic impact in animal models of stroke and can reverse the axonal dysfunction observed in a mouse model of multiple sclerosis. These constructs also have been shown to improve cognitive function and decrease the inflammation associated with exposure to methamphetamine, suggesting a highly effective therapeutic profile. Methamphetamine has been shown to exacerbate the increased infarct volume and decreased cognitive function observed following transient middle cerebral artery occlusion in mice. The direct effects of methamphetamine use on white matter function and vulnerability to ischemia remain unexplored. The primary objective of this STTR proposal is to evaluate our third-generation molecule, DRhQ, which has been optimized for CD74 binding and future clinical use, by determining whether it can reduce or even reverse neuronal and axonal damage caused by methamphetamine use. In Aim 1, we will evaluate whether DRhQ decreases infarct volume and improves cognitive function from methamphetamine-associated stroke. In Aim 2, we will examine the impact of methamphetamine alone on the function of myelinated and unmyelinated axons in the corpus callosum from mice, and then, we will determine whether any reduction in axon function and integrity can be reversed following treatment with DRhQ. At the end of this Phase 1 feasibility study, we will have determined whether DRhQ has the potential to be an effective treatment for neuronal and axonal damage caused by methamphetamine use including whether it can reduce or reverse the severity observed in methamphetamine-associated stroke. If successful, DRhQ may be a valuable therapeutic in treating complications from methamphetamine use. Phase 2 studies would look to expand preclinical testing and work to advance DRhQ into clinical testing.

NIDA - National Institute on Drug Abuse

This project aims to develop software that addresses key challenges in providing care for individuals with serious mental illness (SMI), which is strongly associated with both non-disordered and disordered drug use. The first specific aim is to develop user interfaces to support the execution of Coordinated Specialty Care (CSC). Evidence-based approaches such as CSC have demonstrated clear benefits for treatment of SMI and substance use, but have not yet achieved scale, in part due to the lack of tools to provide continuity of care. Our innovative approach, leveraging Cognitive Task Analysis (CTA), will help address the challenges of coordinating collaborative decision-making and seamless connectivity among providers, patients, and family members who serve as caregivers. The second specific aim is to develop a Large Language Model-based role-playing capability which enables families to practice realistic appointment scenarios in advance. In this domain, families and patients consistently report that appointments are not efficient, and do not foster a sense of collaborative decision-making, instead being focused on catching the provider up on the patient’s symptoms. Through realistic role-playing conversations, families can gain confidence, improve communication skills, and support patients more effectively. Recent advances in LLM research suggest that software can provide a scalable, realistic, high-fidelity, clinically accurate approach sufficient for this task. The proposed approach uses LLMs in combination with novel prompting techniques to minimize the LLM’s propensity to fabricate information, to vet potential statements for clinical accuracy, and to ensure adherence to key principles such as best practices from substance use treatment and CSC. To evaluate the platform's feasibility, usability, and potential impact, this effort includes a formative study with our internal team and a pilot summative evaluation with users, which will pave the way for a full effort to validate the project’s objectives under Phase II. Ultimately, this project has the potential to enhance CSC delivery and improve outcomes for individuals with SMI and substance use issues, thereby reducing and mitigating adverse effects of substance use, and reducing the strain on families as they provide care for patients.

NIDA - National Institute on Drug Abuse

Opioid analgesics (e.g. fentanyl, morphine, oxycodone) are widely used to treat and manage moderate to severe acute pain resulting from trauma or surgery as well as some types of chronic pain. It is well established that these drugs exert their influence through activation of the µ-opioid receptor. Unfortunately, opioids are also highly addictive and physical dependence on these drugs can be established after as little as a few days of sustained use. Between 1999 and 2020, >565,000 people died from an opioid involved overdose, and in 2022 nearly 70% of drug overdose deaths (~74K of ~108K) involved synthetic opioids, primarily fentanyl. In addition, according to the National Survey on Drug Use and Health, ~2.7 million people were suffering with opioid use disorder (OUD) in 2020 and the economic impact of the opioid crisis in the US was ~$1.5 trillion. Although treatments such as Methadone (Dolophine), Buprenorphine (Subutex) and Naltrexone (Revia) are available, only 24% of OUD patients received treatment in 2022 and the risk of relapse is high. The danger of long-term opioid use extends beyond the risk of overdose death, as patient experiencing OUD are at increased risk for a wide range of additional negative health consequences. There is a clear, present, and persistent need to develop novel therapies for OUD. Studies demonstrate that antagonism of the 5-HT7 receptor can regulate key dopamine pathways involved in substance use disorder and improve cognitive flexibility and memory. These improvements are especially noted in assays with links to negative states such as psychosis, depression, stress, and withdrawal. We have identified a series of novel, drug-like 5-HT7 antagonists that include a lead compound, PRA078, which produces a statistically significant reduction in a cue-induced reinstatement rat model of cocaine use disorder. In this program, we will determine the impact of our lead compound on rat models of opioid use disorder. This data will support our continued advancement of this compound into pre-clinical IND enabling studies as a treatment for opioid use disorder.

NIDA - National Institute on Drug Abuse

PROJECT SUMMARY / ABSTRACT Cocaine use disorder (CUD) is a serious public health concern in the United States. Approximately 0.5% of the US population have CUD, and these people are more prone to death, particularly by overdose, suicide, and cardiovascular events. CUD treatment focuses on psychological therapies, which are expensive and only moderately effective. There are no approved medications for CUD, thus identifying novel pharmacotherapies for this disorder is an important unmet need. The long-term goal of this project is to bring to market a safe and effective pharmaceutical drug treatment that leverages novel mechanisms of action to reduce cocaine use and improve abstinence. We have discovered two molecules featuring different mechanisms of action that may plausibly be effective in treating CUD. The current project will evaluate these two compounds for their effects in behavioral models evaluating cocaine- and non-drug-related reinforcement, and stress-induced reinstatement of drug-seeking behavior. Specifically, we will evaluate the ability of these two molecules to reduce the number of cocaine infusions in cocaine self-administration studies based on a fixed ratio schedule of reinforcement. We will then evaluate the most effective molecule in a stress-induced reinstatement assay, which evaluates the ability of the compound to prevent a relapse induced by stress after a drug-free period. If our compound is effective with a single dose, we will examine whether it remains effective at suppressing stress-induced reinstatement after repeated administration. Finally, we will evaluate whether the effects of the compound also modify the reinforcing value of food in a fixed ratio schedule of reinforcement. The resulting data will help us understand to what extent the effects of the compound are selective for drug and non-drug reinforcers.

NIDA - National Institute on Drug Abuse

Project Summary This proposed project aims to address the public health challenges posed by non-disordered drug use through an innovative AI-driven mobile application powered by cloud technology. We propose developing a real-time app that allows drivers to assess their state regarding non-disordered drug use before operating a vehicle, especially focusing on school and college bus drivers in the United States. This app will utilize a multimodal AI framework that analyzes overall facial and body pose features to distinguish between individuals who are under the influence of drugs and those who are not. By employing our advanced transformer-based customized AI framework, the proposed app will assess various facial characteristics, including changes in facial symmetry, gauntness, and overall appearance, which can indicate drug use. The app will provide immediate feedback on the user's fitness to drive and will notify the school/college administration as well the law enforcement authorities when a driver qualifies as fit to operate a vehicle. This cloud-based solution not only enhances detection accuracy but also ensures scalability and accessibility across various devices, ultimately promoting safer driving practices and improving public safety outcomes.

NIDA - National Institute on Drug Abuse

Abstract The opioid epidemic has led to widespread morbidity and mortality, with xylazine, an animal sedative, emerging as a common adulterant in illicit opioids. Xylazine causes severe skin ulceration and necrosis due to its vasoconstrictive effects, resulting in impaired tissue oxygenation and chronic vascular damage. This project aims to develop Chimectin, a first-in- class fibronectin matrix mimetic, as a novel therapeutic to accelerate healing of xylazine- induced skin injuries. Chimectin, a recombinant fibronectin fragment, mimics the structural and functional properties of native fibronectin fibrils, stimulating local vasodilation and promoting revascularization of wounds. In preclinical studies, Chimectin accelerated healing of excisional wounds in a diabetic mouse model. The proposed research will first develop a topical formulation of Chimectin, followed by testing its efficacy in an established preclinical model of ischemic skin ulcers to mimic xylazine-induced vascular damage. The Chimectin formulation will undergo stability and performance testing, with wound healing efficacy evaluated at different concentrations (10, 20, and 40 µM). Successful outcomes will provide the foundation for advancing Chimectin toward clinical development for xylazine-induced and other chronic skin wounds. This innovative therapy aims to address a critical unmet medical need and has the potential to reduce the significant healthcare burden associated with chronic wound management.

NIDA - National Institute on Drug Abuse

Project Summary Smoking, linked to severe health issues and deaths, sees low cessation rates with current therapies due to relapse. Inhaled nicotine, unlike other nicotine replacement therapies (NRT), offers better pharmacokinetics and sensory satisfaction, potentially improving quit rates. Despite growing regulatory support for innovative cessation solutions, no FDA-approved inhaled NRTs exist, revealing a significant market opportunity for new developments. Our latest innovation, Water Inhalable Nicotine (WIN), revolutionizes smoking cessation, featuring an easy-to- use, cartridge-based design for inhaled NRT. WIN utilizes a proprietary water formulation tailored for inhalation, offering rapid and effective nicotine delivery that replicates the sensory satisfaction of smoking. This system is enhanced with an intelligent dose algorithm integrated into a mobile app, supported by a color-coded step-down treatment regimen, enabling personalized cessation strategies. The design ensures minimal inhalation toxicity and environmental impact, while its precise, controlled delivery improves medication compliance and balances abuse liability, making it ideal for adult smokers and underserved populations. This innovative approach positions WIN at the forefront of smoking cessation solutions, combining user safety with environmental responsibility. In Aim 1, we will focus on optimizing WIN’s design for three nicotine strengths (High/Medium/Low) through comprehensive aerosol and chemical characterizations. We will conduct extensive aerosol testing to quantify nicotine emissions under varied conditions and analyze aerosol particle size to ensure optimal lung deposition. Additionally, assessments of harmful constituents such as carbonyls, VOCs, heavy metals, etc. will confirm WIN’s safety and efficacy, aiming for precise delivery and consistent performance. Aim 2 involves in vitro assessments to confirm the safety of WIN by testing its aerosol condensates for cytotoxicity using MTT assays on human alveolar epithelial cells (A549 cell ALI model) and for genotoxicity using Ames tests on Salmonella strains. The goal is to maintain >80% cell viability and achieve <2-fold increase in revertant colonies, aligning with scientific and regulatory benchmarks for further clinical development. Aim 3 seeks to optimize the WIN device's usability by gathering non-identifiable feedback from smokers on various prototypes through anonymous third-party interviews and simulated use scenarios. Feedback will be analyzed to refine UI elements such as mouthpiece orientation, materials, LED display, and app integration, enhancing the device’s intuitiveness and user-friendliness to improve smoking cessation outcomes. To strategically navigate the regulatory pathway, we will consult with experts and schedule a Pre-IND meeting with the FDA, ensuring our strategy aligns with regulatory standards. SBIR Phase II will involve GLP-compliant toxicity tests and a Phase 1 clinical study to assess WIN’s pharmacokinetics and safety, progressing towards FDA approval and enhancing public health by aiding smokers in quitting.