To help guide applicants on the technology areas funded through the program, the major NIDA SBIR/STTR portfolio areas are listed below. Applications proposing innovative technologies related to substance use disorders with strong commercial potential that fall outside these topic areas are also encouraged through this omnibus solicitation. Topics of special interest include:
- Biomarker Development for Substance Use Disorders
Currently, there are no biomarkers usable to assess or predict treatment efficacy or to categorize substance use disorders (SUD) into clinical subtypes. Thus, it is impossible to design effective treatments based on SUD patient categories with reproducible and predictive validity.
Long-term misuse of legal and illicit drugs can change the endogenous receptor systems (e.g., opioid, dopamine, cannabinoid) in the brain and peripheral immune cells. The program is interested in identifying biomarkers or potential predictive markers that could serve as objective prognostic indicators for the development of a SUD, predict adults’ response to SUD therapeutics, or facilitate diagnosis of infants with neonatal abstinence syndrome. The program is also interested in biomarker signatures that predict the course and potential development of a SUD.
The proposed biomarker research should emphasize the importance of biomarker signatures that can intersect a SUD and related conditions that are considered essential to the mission of NIDA. Projects may include proposing biomarkers that assess the probability of a SUD or allow an assessment of the treatment trajectory in patients in treatment for SUDs. Grant applications solely focused on biomarkers for pain in patients with pain not associated with a SUD are of limited interest.
- Drug Discovery and Development for Substance Use Disorders
Pharmacotherapy is an effective means of treating substance use disorders (SUDs). Currently, there are three pharmacotherapies approved by the Food and Drug Administration (FDA) for the treatment of opioid use disorder: methadone, buprenorphine, and extended-release naltrexone. Naloxone is another FDA-approved medication indicated for the emergency treatment of known or suspected opioid overdose. The drug lofexidine is approved to mitigate opioid withdrawal symptoms during detoxification. Varenicline, bupropion, and nicotine-replacement therapies (e.g., nicotine patches, gum, lozenges) are approved to treat nicotine cessation. However, given the diverse nature of a SUD, many patients have limited response to the available medications. In addition, there are no FDA-approved medications for stimulant (e.g., cocaine, methamphetamine) or cannabis use disorders. As a result, the need to develop and evaluate new, more efficacious SUD medications remains a high priority. Candidate medications may include novel and repurposed compounds. Grant applications that propose to study compounds already extensively investigated or currently being studied in patients with SUDs are of limited interest. Grant applications pursuing drug discovery and development for pain should propose the research in the context of SUDs.
Specific areas of interest include medications that target one or more components of the addiction cycle, including reward, stress, negative affect, incentive salience, executive function, habituation, and impulsivity/compulsivity. Compounds may be developed for indications such as preventing the initiation of a SUD, preventing of progression of the severity of a SUD, improving treatment adherence for a SUD, facilitating opioid agonist discontinuation, treating opioid withdrawal, treating neonatal opioid withdrawal, reducing the lethality of opioid or stimulant overdoses, reducing overdose during a return to using or recurrence of SUD symptoms, and reducing the risk of opioid respiratory depression. Additional targets for pharmaceutical development include agents that attenuate excessive substance use and other symptoms of SUDs, e.g., cravings, sleep problems, and negative affect, as well as those that hold promise for the treatment of tobacco, cannabis, cocaine, methamphetamine, heroin, or prescription opioid use.
Proposed projects may include applying emerging and existing technologies and platforms for SUD medication development, focusing on products with the potential to minimize drug use, address symptoms associated with addiction (such as disordered sleep), and prevent and reverse overdoses. Topics of interest include:
- Early therapeutic discovery activities ranging from target identification and validation through lead development
- Preclinical and/or clinical drug development
- Technologies or formulations to improve medication delivery or long-acting formulations of existing addiction medications
- Medications that address specific symptoms of withdrawal, such as cravings, depression, cognitive impairments, pain, and sleep problems
- Medications that, while not addressing addiction directly, target significant risk factors for a return to use such as insomnia, dysphoria, and depression
- Medications (neurochemicals) involved in social bonding that also modulate key processes associated with addiction, including reward and stress responses, and may enhance the efficacy of psychosocial addiction treatments
- Big data analytics and machine learning algorithm analysis yielding insight into behavioral and biological markers of a return to use risk, tools, or devices to avert recurrence of SUD symptoms
The Target Product Profile (TPP) is an important planning tool for developing a drug candidate from discovery to clinical development programs. Routinely, the TPP is designed in a format to summarize a drug development program described in terms of concepts and characteristics listed on the drug label. With the TPP, a drug developer specifies the labeling concepts that are the goals of the drug development program and documents the specific studies that are intended to support the labeling concepts, which could then be used to assist in a constructive dialogue with the FDA. TPPs are productively used in advanced translational programs at NIH, and the published examples of TPPs can be found here: https://neuroscienceblueprint.nih.gov/sites/default/files/documents/tpp-worksheet_508c.pdf. Frequently, pharmaceutical companies establish TPPs with marketing attributes integrated into the framework of the drug's labeling concepts. In this case, the tool guides clinical development decisions and directs the foundation for marketing success. The TPP also contributes to the ultimate goal of driving greater efficiencies and shorter timelines to approve an optimally marketable and profitable product. Applications proposing the development of pharmacotherapeutics for SUD are strongly encouraged to use the TPP as part of their development and commercialization strategy.
- Technologies for Safe and Controlled Methadone Dispensing for Use at Home
More than 350,000 Americans are prescribed methadone maintenance treatment (MMT)1 to treat opioid use disorder. By law, methadone to treat OUD can be administered or dispensed only through an opioid treatment program (OTP) that is certified by the Substance Abuse and Mental Health Services Administration (SAMHSA) and registered by the Drug Enforcement Administration (DEA). According to SAMHSA, methadone can be administered as a pill or a liquid. Patients must report to OTP centers to receive the medication, often daily. In most OTPs, the patient receives a daily dose of liquid methadone, with doses adjusted and tailored to the patient’s needs to reduce withdrawal symptoms and opioid cravings. Some of the significant barriers to methadone treatment are the restricted availability of timeslots at OTP centers for daily dosing and logistical constraints, and associated costs (e.g., travel from/to OTP centers).
In some circumstances, patients may be provided with take-home methadone doses for unsupervised use at home instead of requiring them to return to the clinic the next day for observed dosing. Take-home methadone prescribing is not available to every patient, is time-limited, and requires a specially designed lockbox for safe storage.
With take-home methadone, there are concerns related to treatment adherence, possible misuse and diversion, and patient vulnerability to theft and violence. Consequently, there is an urgent need for a comprehensive technological solution to continually assess the efficacy and safety of this medication strategy. There is also a need for an integrated solution explicitly addressing the intricacies of the methadone clinic, which combines multiple technological innovations and provides both OTP centers and patients with answers that allow for safe and effective MMT and secure access to take-home medication while reducing the burden and stigma that accompanies the current process.
Specific aspects of take-home technologies or approaches for MMT may include, but are not limited to, the following:
- Remote tracking of medication adherence
- Remote dose and time-controlled dispensing
- Personalized secure access to the medication dispenser
- Tamper-proof access to medication
- Digital health solutions that allow for patient-provider interaction (e.g., reminders for patients, telehealth solutions for providers)
- Deactivation of methadone in case of diversion or theft
Proposed tools and technologies should take into full consideration the unique legal, public health, and community aspects of MMT.
- FDA-regulated Medical Devices for Substance Use Disorders
Medical devices, including digital therapeutics, offer a promising means to monitor, diagnose, and treat substance use disorders (SUDs). Currently, there are only a few medical devices cleared by the Food and Drug Administration (FDA) for the diagnosis or treatment of a SUD. The evaluation and development of new medical devices that are safe and effective are a high priority. Applications are expected to address the needs of patients who have SUDs, and their caregivers, to ensure access to safe, effective, high-quality medical devices. Proposed activities are expected to lead to regulatory submissions for premarket clearance/approval with the FDA through the following pathways: pre-submission (Q-submission), investigational device exemption (IDE), 510(k), De Novo, or Premarket Approval (PMA) application. Additional preclinical activities may include, but are not limited to, the following:
- Bench testing or computational modeling studies
- Animal studies
- Good manufacturing practice (GMP) studies
- Toxicology, biocompatibility studies
Specific areas of interest:
- Imaging devices intended to investigate brain function and enhance monitoring and diagnosis of SUDs
- Devices that directly diagnose and/or reduce craving and withdrawal symptoms
- Devices that identify and/or treat neonatal opioid withdrawal syndrome (NOWS), also referred to as neonatal abstinence syndrome (NAS)
- Digital therapeutics focused on behavioral health interventions to alleviate the burden of SUDs
- Therapeutic devices (e.g., neuromodulation) intended to improve SUD treatment outcomes and return to use prevention
- Diagnostic devices used to detect and monitor opioid-induced respiratory depression
- Physiological monitoring devices (e.g., wearables) specifically intended for use by patients with SUDs
- Technological Approaches to Address Stigma Associated with Substance Use Disorders
The stigma against people with substance use disorders is a set of negative attitudes and stereotypes that can create barriers to treatment and make these conditions worse. Stigma may be internalized (personal endorsement of prejudice and stereotypes), enacted (experiences of discrimination from others), or anticipated (expectations of discrimination from others in the future, even if one has not experienced discrimination in the past).
Applicants are invited to propose projects demonstrating how the latest technology and evidence-based science could meaningfully reduce the stigma associated with SUDs. NIDA is especially interested in research with commercial potential that aims to reduce SUD stigma in the adolescent population and research on the effects of providing anti-stigma training to medical professionals and nonmedical providers (social workers, criminal justice, family members, and educators).
Examples of technological approaches:
- The use of neuromarketing tools and services to help develop and disseminate the most effective anti-stigma campaigns
- Digital compassion (anti-stigma) coaching for medical professionals delivering treatment to patients with SUDs
- Digital certification program for nonprofessional caregivers who provide support services for patients with SUDs
- Virtual employee assistance programs focused on SUDs and mental health that provide employees with support for issues that affect their well-being and enhance the effectiveness of a drug-free workplace program
- Digital Health Technologies to Address the Social Determinants of Health in the Context of Substance Use Disorders
Public health experts have long recognized the impact of social determinants on health outcomes, including SUD. According to the World Health Organization (WHO), social determinants of health (SDH) are the conditions in which people are born, grow, live, work, and age. Social determinants can directly shape health risk behaviors and manifest in the living conditions and resources that indirectly exacerbate the consequences of drug use. For example, inadequate housing can increase the likelihood of infectious disease transmission, while, conversely, a safe and clean neighborhood can increase the possibility of individuals accessing appropriate and supportive healthcare.
A full spectrum of interventions encompassing both SDH and individual-level factors should be considered to fully address the addiction and overdose crisis in the United States. Digital solutions can offer a new path forward in addressing SDH in drug addiction. These solutions provide evidence-based, continuous, and accessible experiences for individuals affected by drug use or living with SUDs. The advantages of digital technology also lie in its capacity to accommodate the changing context and environments that contribute to the 21st century SDH: new means of communication and mobility, new cultural contexts, new consumer behaviors, and new family and community dynamics.
Eligible small businesses can submit grant applications focused on transforming family, housing, employment, justice, and educational determinants of drug use. The proposed products should offer the most far-reaching and promising opportunities for the intended customers and end-users to contribute meaningfully to addiction and the opioid crisis.
Topics could include, but are not limited to, the following:
- Research, design, and validation of novel tools and approaches to address food and housing insecurities
- Research and design of novel tools to enable impactful housing programs that promote health (for example, the innovative housing programs that can co-locate employment, education, and behavioral health services)
- Design and validation of curriculum for soft skills(e.g., clear communication and emotional intelligence) development for addiction treatment providers
- Novel educational tools/novel educational delivery systems to foster compassion and eliminate the stigma associated with SUD
- Research and design of preventive systems for families to promote healthy behaviors, social skills, community opportunities, and productive social involvement
- Novel educational tools/novel didactic delivery systems focused on social stability (community, tradition, faith, family), self-regulation, and resilience
- Novel educational tools/novel didactic delivery systems to focus on happiness, well-being, belonging, positive, and fruitful communal life
- Design and validation of technologies that help create and enhance productive social support networks that facilitate recovery, engagement with care, and/or access to needed services
- Research and design of tools and technologies to help facilitate continuity of care, access to services, and prosperous community reintegration for people reentering communities following a period of incarceration
- Development of technology to facilitate data sharing among organizations that serve justice-involved individuals to increase coordination of services, enhance service quality, and/or increase engagement with effective services
- Research, design, and validation of novel approaches for job training (e.g., entrepreneurship, financial literacy, IT skills), especially for approaches delivered in recovery housing or while incarcerated
- Develop and validate the best practices for employer education and support to allow employers to hire, retain, and facilitate treatment for employees seeking help for SUDs
- New Technological Approaches for the Investigation, Diagnosis, and Certification of Deaths Related to Drug Overdose
Research proposals are needed to deliver devices and technologies to improve reporting and collection of mortality data related to drug overdoses, as drug overdose mortality counts for specific drugs may be underreported.2 NIDA is interested in technologies and diagnostic devices that improve and accelerate the work involved in death scene investigation, autopsy, toxicological analysis, and certification of death. Enhanced surveillance of fatal overdoses will give those in public health, public policy, research, and government the ability to identify threats in a timely manner and implement effective interventions in communities impacted by drug overdose.
Specific areas of interest:
- Curation and digitizing of the jurisdiction-dependent practices and protocols
- Improved tools to alleviate test backlogs
- Tools to improve communication and coordination among forensic pathologists, hospitals, and lab technicians (medical examiner/coroner)
- Improved methods to minimize the risk of infection with blood-borne pathogens (e.g., Hepatitis C or HIV) while performing the autopsy and toxicological analysis
- Qualitative tests to determine a therapeutic vs. toxic vs. lethal dose
- Rapid techniques and devices for field use
- Improved immunoassays (e.g., to include urine, to decrease the number of false positives and negatives)
- Testing technologies with the ability to accommodate changes in the new drug of choice
NIDA hopes that the development of these tools will improve the detection and reporting of opioid-related deaths. Improved surveillance will reveal the magnitude of opioid-related deaths more accurately, thus clarifying attempts to decrease the number of opioid-related deaths and improving public health by monitoring the effects of these interventions.
- Alderks CE. The CBHSQ Report. Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration; 2017. Accessed January 19, 2022. 8
- Boslett AJ, Denham A, Hill EL. Using contributing causes of death improves prediction of opioid involvement in unclassified drug overdoses in US death records. Addict Abingdon Engl. 2020;115(7):1308-1317. https://doi.org/10.1111/add.14943