Stigma around Substance Use Disorders (SUDs) represents a significant public health problem, despite growing understanding that SUDs are complex brain disorders with behavioral and physiological components. Recent scientific discoveries indicate that susceptibility to the brain changes in SUDs is substantially influenced by factors outside an individual’s control, such as genetics or the environment in which one is born and raised. Similar to other disorders, medical care is often necessary to facilitate recovery and prevent negative outcomes, including overdose. SUD is a chronic, treatable disease from which patients can recover and lead healthy lives, however stigma limits successful access to care. Nevertheless, stigma can be changed, instilling a sense of hope, and self-efficacy for change that contributes to this recovery. Stigma is understood as a socially constructed phenomenon that occurs when members of a group experience status loss or discrimination on the basis of some shared characteristic that is deemed undesirable by others. Its effects can occur through attitudes and beliefs internalized by stigmatized individuals (self-stigma), through overt discrimination by others (experienced or enacted stigma), and through the fear of such discrimination (felt stigma). As a result, many people are reluctant to disclose, seek treatment or even talk about substance use disorders, which leads to diminished access to treatment or decreased ability to receive adequate care. There have been promising advances in reducing stigma around other health conditions, for example depression or HIV, making these conditions more acceptable to discuss and breaking down barriers to treatment. Recently, the opioid epidemic impacted all levels of society in the United States and began to shift attitudes about SUD-related stigma as well. The Patient Protection and Affordable Care Act in 2014 has enabled the health care providers to offer reimbursable treatment services for SUDs. However, only 11% of patients that meet the criteria for substance use disorder receive treatment. SUD- related stigma is one of the important factors contributing to this persistent gap; therefore, mitigating stigma will facilitate SUD prevention and care. In addition, addressing SUD stigma will help to improve prevention and care for HIV and other SUD comorbidities such as HCV and sexually transmitted infections (STI). There is significant evidence that stigma undermines both mental and physical health. It may make people feel badly about themselves, leading to or exacerbating depression, anxiety, and other mental health issues or substance use. Stigma or negative bias among those healthcare providers who perceive a patient’s drug or alcohol problem as the patient’s own fault can lead to substandard care. People showing signs of acute intoxication or withdrawal symptoms are sometimes expelled from emergency rooms by staff suspecting drug-seeking behavior. The general public and some in healthcare and the justice system continue to view SUD as a result of moral weakness and people with addiction are continued to be blamed for their disease. Humiliation and rejection experienced by patients stigmatized for their drug use is a powerful social punishment. People with addiction may internalize this stigma, feeling shame and refusing to seek treatment. The health impact of stigma is magnified by the scarcity of available treatment options in rural and low-resource environments. Beyond being a barrier to care, stigma may enhance or reinstate drug use, playing a key part in the vicious cycle of addiction. SUD-related stigma is often intersectional with negative bias, discrimination, and other forms of stigma. They may include homelessness, socio-economic status, race and ethnicity, gender identify, mental illness, and/ or HIV. Negative bias may prevent parents from talking to their children about risks of substance use, screening for SUD, and seeking out or supporting treatments. Given that SUD and mental health conditions often start to manifest in early adolescence, stigma may result in missing crucial prevention and early treatment steps. Clinics and social care settings may create inhospitable environments to some SUD patients, where stigma can arise from policies and practices, behaviors of insufficiently trained non-clinical staff and sometimes clinical providers. Stigma remains one of the most important barriers to provision and utilization of prevention and care services for HIV and other SUD comorbidities, despite advances in diagnostics, prevention and treatment. Organizational and interpersonal stigma has a disproportionately large impact on access of SUD patients to treatment or life-saving procedures at the time of resource shortage due to disasters, for example the COVID19 pandemic. Demonstrated similarities in drivers and outcomes of health-related stigma across different domains suggest that successful interventions developed to address stigma in other areas (i.e. HIV, mental health) could provide conceptual support to anti-stigma efforts in the SUD field. Not all anti-stigma interventions are effective (despite demonstrated public reach); they may fail to reduce stereotype agreement, desired social distancing or even “backfire” (increase stigma). It has been suggested that certain personality traits may mediate resistance to anti-stigma campaigns. Focused interventions are required for specific age and cultural background subgroups. For example, cognitive mechanisms influencing messaging efficacy in adolescents may differ from those in adults; culturally appropriate community-based interventions have been critical to connecting American Indian and Alaskan Natives (AI/AN) to mental and behavioral health; and interventions for pregnant and parenting mothers with SUDs had to take into account the legal consequences of seeking SUD treatment. Recent studies of neural mechanisms of successful quitting campaigns and deeper understanding of neural circuitry underlying behavior change open new opportunities to identify, personalize and optimize anti-stigma interventions. In particular, fMRI activation of medial prefrontal cortex (MPFC) has been demonstrated to be more predictive of the success of selected health promotion messages than self-reports. Non-invasive EEG based classifier has been developed predicting (smoking) treatment success as another example of neural target-based behavior change approach. Intracranial EEG (iEEG) was successfully used in the research environment to describe components of the “brain valuation system”. Ventral striatum, inferior orbitofrontal cortex and ventromedial prefrontal cortex have been identified by an fMRI as components of a valuation system linked to the likelihood of behavior change. Interactive training and behavioral interventions delivered via immersive/ extended reality (XR) technologies are effective in reaching outcomes. This training could be further strengthened by the latest “serious” gaming approaches. This funding opportunity (FOA) seeks to combine novel technologies with evidence-based stigma reduction interventions to reduce stigma around SUD as a primary outcome, leading to reduced barriers to SUD prevention, treatment, and support during recovery long-term. Research Objectives. The goal of this initiative is to reduce stigma around substance use disorders (SUDs) by leveraging breakthrough technologies and the latest science to develop and commercialize products and services. To be responsive, grant applications submitted in response to this FOA should combine (1) the latest technology; (2) evidence-based science; (3) a method to demonstrate that the stigma to SUD will be reduced; and for Fast Track and Phase II show (4) potential measures of’ impact on SUD treatment intake, retention, and other outcomes. Applications may address individual (internalized, anticipated, or enacted), interpersonal, organizational, and/or structural levels of stigma. Applications and focus can be on any entry point along the continuum of care. Areas of specific research interest and SUD service contexts include, but are not limited to: providing anti-stigma training for medical professionals; targeting stigma reduction of non-medical providers (social workers, criminal justice, family members, and educators); anti-stigma training specific to adolescent substance use and prevention; enhancing both employee well-being and effectiveness of a drug-free and stigma-free workplace program. Technologies or approaches may include, but are not limited to: Natural Language Processing (NLP), Computer Vision (CV) and other Machine Learning (ML) tools to detect and analyze provider behaviors and medical records reflecting stigma around SUD alone and intersectional stigma; Digital compassion (anti-stigma) coaching for medical professionals delivering treatment to SUD patients exploring immersive technologies such as extended reality (XR); Digital certification program for nonprofessional caregivers who provide support services for patients with SUD; Virtual employee assistance programs with focus on SUD and mental health; Ecological momentary sampling and other digital phenotyping patient-centered tools to detect points of vulnerability and counteract internal stigma supporting the whole-person model of recovery; Neural activity-based tools and services to help develop and disseminate the most effective anti-stigma campaign. The SBIR/STTR program is a phased program. The main objective in SBIR/STTR Phase I is to establish the technical merit and feasibility of the proposed research and development efforts, whereas in SBIR/STTR Phase II it is to continue the R&D efforts to advance the technology toward ultimate commercialization. An overall objective of the SBIR and STTR programs is to increase private sector commercialization of innovations derived from federally supported research and development. At the conclusion of an SBIR/STTR Phase II, it is expected that the small business will fully commercialize their product or technology using non-SBIR/STTR funds (either federal or non-federal). Two types of applications are accepted in response to this FOA: Phase I. The objective of Phase I is to establish the technical merit, feasibility, and commercial potential of the proposed R/R&D efforts and to determine the quality of performance of the small business awardee organization prior to proceeding to Phase II. Fast-Track (Phase I/ Phase II) applications should include clear rationale of feasibility of the proposed approach and/ or technology application in SUD area; demonstrate a high probability of commercialization; propose clear, appropriate, meaningful and measurable goals (milestones) to be achieved prior to initiating Phase II; and indicate potential Phase III support/interest (non SBIR/STTR) from future commercialization partners. An NIH SBIR Fast-Track incorporates a submission and review process in which both Phase I and Phase II applications are submitted and reviewed together as one application to reduce or eliminate the funding gap between phases. The objective of Phase II (as a part of Fast Track applications) is to continue the R&D efforts initiated in Phase I to advance technologies to potential commercialization. Projects proposed for Phase II are based on the results achieved in Phase I (or equivalent) and aim to demonstrate scientific and technical merit and commercial potential. NIDA seeks to determine that both technical feasibility and commercial feasibility are established in Phase I before making the decision about proceeding to Phase II.