Developing new and improved substance use interventions for prevention and treatment is a top priority for NIDA, particularly interventions that are feasible to implement, cost-effective, and informed by insights of the people who will benefit from them. This includes supporting research to prevent substance use initiation and the escalation to SUDs for individuals across the life span. NIDA is also prioritizing research to prevent overdose, drug-related infectious disease, and other serious adverse outcomes of drug use. In addition to advancing research on prevention, there is an urgent need for additional SUD treatments. While abstinence may be a treatment goal for some individuals, interventions that reduce use, protect against adverse health consequences, address related symptoms such as withdrawal, or improve overall health are also important outcomes and priorities for NIDA-supported research. NIDA has also significantly expanded its investment in science to inform evidence-based approaches to recovery support and build the science of recovery itself. NIDA is committed to advancing innovative research across the continuum of SUD care to support national and community-level efforts to address the drug landscapes that drive substance use and SUD and the current overdose crisis.
- Goal 2.1: Develop and test novel strategies for preventing drug use, SUDs, and their consequences
Decades of NIDA-supported research have illuminated biological, developmental, and environmental risk and protective factors for substance use and SUD. This knowledge has informed the development of an array of effective interventions for preventing substance use initiation, the transition from use to SUDs, and the adverse consequences of substance use, including overdoses and infectious diseases.
Early substance use can create problems in school and with family, make it difficult to meet the increasing demands of maturation, and increase the risk of developing SUDs as a young adult. Data show that some effective interventions can be delivered in early childhood and even during the prenatal period (e.g., nurse home visitation of pregnant women). Because substance use often begins during adolescence and young adulthood, this is also a critical period for prevention. Indeed, for youth, prevention interventions aimed at reducing risk, promoting resilience, and identifying and addressing substance misuse at an early stage can have effects that go well beyond reducing later substance use to encompass many other behavioral health benefits. Moreover, longitudinal studies that track the effects of preventive interventions across the lifespan and even across generations demonstrate the long-term positive impact of preventive approaches early in life. NIDA has a robust prevention portfolio and leads programs within the NIH Helping to End Addiction Long-Term® (HEAL) Initiative focused on preventing opioid use and escalation to OUD among young people in school settings and justice settings, where substance use is a significant factor for reinvolvement with the legal system.
Preventive interventions can also be effective for other groups, including adults and pregnant women. Yet despite strong evidence for the effectiveness of individual-, family-, and community-level prevention strategies, relatively few such interventions have been widely adopted or faithfully implemented, and thus their potential to positively impact public health has been limited. Further, research shows that how a program is implemented can determine its effectiveness and that prevention interventions must be tailored to meet the needs of specific populations in various settings. Therefore, NIDA is prioritizing research to develop interventions that can be implemented across systems, including in education, human services, and health care, where there is greater potential for uptake, scalability, and sustainability.
Prevention of overdose and other adverse consequences of substance use is a priority for NIDA. Overdose deaths are significantly reduced in communities that distribute naloxone to people who use drugs and to their families or other potential bystanders. Interventions to reduce the spread of HIV, HCV, and other infectious diseases, and link people to infectious disease testing and care, are also important, including integrated pre-exposure prophylaxis (PrEP) delivery and highly active antiretroviral therapy (HAART) to reduce HIV/HCV transmission. Through the HEALing Communities Study, researchers used community-based approaches to deliver opioid treatment and overdose education, combined with naloxone distribution to prevent opioid overdose. Other studies are exploring new models for preventing the spread of infectious diseases, including in rural communities vulnerable to opioid injection-related HIV outbreaks, and examining whether integrated health services delivered through mobile clinics improve outcomes for both HIV and SUDs. NIDA will continue to support research to test the efficacy and implementation of these and other strategies for preventing risky drug use and its adverse consequences.
Key Focus Areas
- Identify and target pathways or mechanisms for preventing substance use and SUDs, including those common to SUDs and other mental illnesses, across the lifespan.
- Develop interventions that enhance resilience and buffer against stressors to prevent substance use and promote healthy behavior across the lifespan.
- Evaluate the sustainability of prevention interventions.
- Develop interventions for populations who are at especially high risk for drug use and SUDs.
- Develop interventions to prevent the progression of substance misuse to more harmful use or SUDs.
- Address knowledge gaps identified by the U.S. Preventive Services Task Force, including research on screening and interventions for unhealthy drug use.
- Evaluate effectiveness and safety of novel approaches to decrease overdose and other adverse consequences of drug use.
- Determine the effectiveness of prevention education and service provision in novel settings.
- Develop and evaluate strategies to reduce risks associated with stimulant use disorders and polysubstance use.
- Goal 2.2: Expand the range of treatment options for SUDs and their consequences
NIDA supports research on pharmacological and non-pharmacological approaches for treating SUDs and overdose, including the development of medications, immunotherapies, digital therapeutics, neuromodulation, and behavioral treatments. This work has led to several effective interventions, including the nasal formulation of naloxone to reverse opioid overdose; buprenorphine and naltrexone, which along with methadone, are FDA-approved medications for treating OUD; lofexidine to treat the symptoms of opioid withdrawal; and nicotine replacement therapy, bupropion, and varenicline for treating tobacco use disorder.
Despite these successes, a much wider array of treatments for SUDs and overdose is still needed. Due in part to the complex nature of addiction and the unique needs of patients, medications for OUD and tobacco use disorder do not work for everyone who needs them. Moreover, no FDA-approved medications exist for stimulant use disorders, cannabis use disorder, or poly-SUDs, making these important areas of research focus. Developing new overdose-reversal drugs that are effective against fentanyl and opioids used in combination with stimulants and other drugs will also be vital for combating the drug overdose crisis. In addition to exploring novel therapeutic strategies—including the use of psychedelics, cannabinoids, and kratom among others as potential SUD treatments, NIDA will continue to support research to repurpose existing FDA-approved compounds as SUD treatments, an approach that could significantly expedite the drug development process (see callout box, “Medications Development for Opioid and Stimulant Use Disorders and Overdose”).
Non-pharmacological treatments are also valuable, alone and in combination with medications, and decades of NIDA-supported research have led to the development of effective interventions. For example, NIDA-funded research established the efficacy and cost-effectiveness of contingency management for methamphetamine use disorder, led to the first “digital medicines” to receive FDA approval for the treatment of addiction, and supported the development of other commercial products to intervene on SUDs and their consequences (see table “Health Technologies Developed with NIDA Support”). NIDA is also leveraging neuromodulation techniques, such as transcranial magnetic stimulation, direct current stimulation, peripheral nerve stimulation, and deep brain stimulation, to develop treatments for reducing cravings, withdrawal, and drug use.
As NIDA’s portfolio evolves, there are increasing opportunities to make SUD treatment more holistic, nuanced, and dynamic, similar to current approaches for other mental and physical disorders. This includes identifying additional endpoints in clinical trials, beyond abstinence, to define successful treatment. Reducing opioid use, for example, would lessen the risk of overdose even if an underlying OUD persists. Reducing cravings, withdrawal symptoms, depressive symptoms, and anxiety or improving poor sleep are other approaches that could reduce substance use. Treating medical consequences of substance use, such as neonatal abstinence syndrome, is also essential to addressing the addiction public health crisis and is a key priority for NIDA. Developing personalized approaches to treatment that account for individual preferences and needs as they may change over time is also key.
Key Focus Areas
- Develop new overdose-reversal medications for fentanyl and stimulants and their combinations as well as devices to detect and rapidly reverse overdoses.
- Develop new formulations of existing medications to improve the treatment of OUD or overdoses.
- Develop novel medications for the treatment of all SUDs including poly-SUD.
- Advance immunotherapies, including monoclonal antibodies, and other biologics.
- Explore neuromodulation techniques, such as transcranial magnetic stimulation, transcranial direct current stimulation, peripheral nerve stimulation, low intensity focused ultrasound, and deep brain stimulation.
- Identify and validate new patient-centered endpoints for clinical trials, including those that address symptoms of SUDs.
- Develop and evaluate personalized treatments.
- Develop new treatment strategies that address the particular needs of adolescents.
- Accelerate research on medical consequences of drug use, including neonatal abstinence syndrome, pain, and co-occurring infections.
- Apply cutting-edge data science methods to capture and analyze patient data and develop new diagnostic, prognostic, and clinical decision support tools.
- Develop and test new digital health technologies to deliver novel prevention, treatment, and recovery interventions.
Medications Development for Opioid and Stimulant Use Disorders and Overdose
While effective medications exist for OUD (e.g., buprenorphine, methadone, naltrexone), these medications are underutilized. More options are needed to help people with OUD achieve long-term recovery, and NIDA is funding innovative projects to develop improved formulations, such as extended-release methadone and buprenorphine that could improve treatment retention and reduce diversion. In addition, NIDA is supporting basic science research that could lead to novel pain management medications with reduced addiction liability.
NIDA leads the Novel Therapeutic Options for Opioid Use Disorder and Overdose program with funding from the NIH HEAL Initiative®, which has already resulted in more than 30 Investigational New Drug applications filed with the FDA and authorized for human studies. These studies focus on a variety of drug targets as well as immunotherapies. Others are repurposing existing medications for OUD indications, such as the FDA-approved insomnia medication suvorexant, based on known overlaps between brain signaling systems involved in sleep and addiction. Due to the increased prevalence of fentanyl in the United States and its uniquely dangerous properties, NIDA is leading research to develop treatments specifically for fentanyl addiction and overdose, including a monoclonal antibody to prevent fentanyl from entering the brain. Research into non-opioid medications is also ongoing to increase available treatment options, with a new focus on polysubstance use to address the reality that most people with OUD also use other substances.
Overdose deaths involving stimulants continue to climb, yet there are currently no FDA-approved medications for stimulant use disorders. NIDA’s Clinical Trials Network (CTN) demonstrated that bupropion plus naltrexone was effective for reducing methamphetamine use and craving in individuals with moderate to severe methamphetamine use disorder. This is one of NIDA’s highest priorities, with current research spanning novel biological targets for new medications, anti-cocaine and anti-meth immunotherapies and sequestrant drugs, and the repurposing of existing medications.
- Goal 2.3: Advance the science of recovery support
While recovery from SUDs means different things to different people, NIDA defines recovery as a process of change through which people improve their health and wellness, live self-directed lives, and strive to reach their full potential. For some, this may mean complete abstinence; for others, recovery could be developing effective coping strategies, improving physical and mental health, or experiencing some combination of those or other outcomes.
Recognizing that there are different paths to recovery, NIDA research is exploring numerous recovery strategies, such as family-based support networks for youth, peer recovery support models, virtual reality-based mindfulness, and other digital health approaches, as well as strategies tailored to specific populations and settings. NIDA is also working to enhance infrastructure to study recovery support services by supporting recovery research networks that include researchers, payors, individuals in recovery, and other stakeholders. In addition to developing effective recovery strategies, it is necessary to address the many barriers that keep people with SUDs from receiving the ancillary services (e.g., housing, transportation, job-related support) and care that they need to achieve and sustain long-term recovery.
Key Focus Areas
- Understand the mechanisms by which recovery support groups exert their effects.
- Support research on different pathways by which people recover from SUDs.
- Incorporate a broader range of clinical outcomes in recovery research, such as improved quality of life and health or reduction in risk behaviors and medical consequences.
- Develop and refine research methods for evaluating recovery support services, and support research on the efficacy of these services.
- Develop novel interventions for sustained recovery that target factors that increase vulnerability for relapse.
- Investigate the impact of environmental factors on recovery.