2022-2026 NIDA Strategic Plan
Priority Scientific Area #2: Develop and Test Novel Prevention, Treatment, Harm Reduction, and Recovery Support Strategies

Developing evidence-based interventions to prevent substance use initiation or escalation to SUDs, treat those who have already developed SUDs, reduce adverse outcomes associated with drug use, and support long-term recovery of people following treatment are top priorities for NIDA research. To speed progress toward these goals, interventions must not only be feasible and cost-effective to implement but they must also be informed by the lived experience of the people who will benefit from them. Given the increasingly contaminated illicit drug market, it is more urgent than ever to prevent, or even delay, early drug experimentation to reduce the risk of adverse outcomes. 

A similar harm reduction mentality should apply to drug treatment and recovery. While abstinence may be a goal for some individuals in SUD treatment, approaches that reduce use, minimize harms, and address related symptoms can contribute in important ways to improving health and quality of life. NIDA will continue to support research to evaluate effective harm reduction approaches, such as preventing and reversing drug overdoses as well as mitigating the spread of HIV and other infections. Further, there is an urgent need for science to inform evidence-based approaches to recovery support, which can take multiple forms and may require different supports at different times—from behavioral coping strategies to secure housing, employment, and transportation. Prevention, harm reduction, treatment, and recovery are all central to national and community-level efforts to address the current drug crisis, and NIDA is committed to advancing innovative research in each of these areas.

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 social-environmental factors that increase the risk of substance use as well as the many factors that can be protective. Knowledge about risk and protective factors has informed the development of an array of effective interventions for preventing substance use initiation and the transition from use to SUDs. 

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 evince 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 or escalation to OUD among students in school settings and in 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 on new interventions to target these factors in diverse systems, including education, human services, and health care, where there is greater potential for uptake, scalability, and sustainability. 

We've got to create spaces in our schools where we can train people to talk to our children, because they want to talk... When I shut my mouth and open my ears, these kids tell me what they need. Until we can start just asking 'Why?' and not 'What's the matter with you?' we're not going to solve it. And I think the school is the best place to solve this." - Michelle Lipinski, Principal at a Recovery High School

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.
  • Develop and evaluate preventive interventions in settings where they are intended to be delivered to decrease the research-to-practice gap.
  • 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 use to more harmful use or SUDs.
  • Support studies to address knowledge gaps identified by the U.S. Preventive Services Task Force, including research on screening and interventions for unhealthy drug use.
Goal  2.2: Accelerate the science of harm reduction 

Abundant research shows the value of interventions and services aimed at reducing harms associated with drug use. Overdose deaths are significantly reduced in communities that distribute naloxone to people who use drugs and to their families or other potential bystanders, and syringe-services programs (SSPs) reduce the spread of HIV and other infectious diseases like HCV, and they help link people to addiction and infectious disease screening and treatment. 

NIDA supports extensive research on SSPs, including on the expanded provision of sterile syringes, HIV/HCV testing and linkage to care, and integrated pre-exposure prophylaxis (PrEP) delivery and highly active antiretroviral therapy (HAART) to reduce HIV/HCV transmission as well as to prevent overdose. Through the HEALing Communities Study, researchers are using novel community-based approaches to deliver opioid treatment and overdose education, combined with naloxone distribution to prevent opioid overdose. Other studies are exploring models to initiate buprenorphine maintenance treatment in SSPs, implement SSPs in rural communities vulnerable to opioid injection-related HIV outbreaks, and examine whether integrated health services delivered through mobile clinics improve outcomes for both HIV and SUDs. Still other studies are examining the effects of harm reduction policies on public health. NIDA will continue to support research to examine how best to implement effective harm reduction strategies and to explore the effectiveness of novel approaches such as overdose prevention centers and drug-checking technologies.

Key Focus Areas

  • Identify and address individual-, policy- and system-level barriers to harm reduction services. 
  • Evaluate the effectiveness and safety of novel harm reduction approaches such as overdose prevention centers and drug-checking technologies.
  • Determine the effectiveness of harm reduction education and service provision in novel settings.
  • Develop and evaluate harm reduction strategies for stimulant use disorders and polysubstance use.
  • Evaluate the role of stigma and other social determinants of health on harm reduction services.
Goal 2.3: Expand the range of treatment options for SUDs and their consequences 
"I am... in recovery and one reason I am alive today is because of Narcan/Naloxone.  I am able to share my story of addiction and my recovery because Naloxone game a second chance at life." - Christina, individual in recovery

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 concurrent 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 drug will also be vital for combating the drug overdose crisis. In addition to exploring novel therapeutic strategies—including the use of psychedelic, cannabinoid, and kratom compounds 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 below, “Medications Development for Opioid and Stimulant Use Disorders and Overdose”)

"Buprenorphine saved my life. I struggled with heroin for 16 more years than I wanted to, until I found buprenorphine. I'm a huge believer in it." - David, person in recovery and advocate

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. 

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. Suboptimal patient retention in treatment regimens, policy barriers that limit prescribing, and stigma around opioid agonist medications all contribute to their underutilization. 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, reduce diversion, and help address the stigma associated with medications for OUD. 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 vaccines and monoclonal antibodies. 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 vaccine 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 vaccines, and the repurposing of existing medications.  

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 as well as devices to detect and rapidly reverse overdose. 
  • Develop new formulations of existing medications to improve the treatment of OUD. 
  • Develop novel medications for the treatment of all SUDs and concurrent SUDs, including concurrent alcohol use disorder.
  •  Advance immunotherapies, including vaccines, monoclonal antibodies, and other biologics.
  •  Explore neuromodulation techniques, such as transcranial magnetic stimulation, peripheral nerve stimulation, 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 treatment strategies for adolescents across the continuum of care
  • 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.
Goal 2.4: Advance the science of recovery support
"He was ashamed of his addiction and always thought he could beat it on his own... He used alone and died alone." - Betsy, mother who lost son to overdose.

"After 20 years of keeping secrets, recovery did not automatically start when I got sober. I had to start opening up about it." - David, individual in recovery

"The stigma of having a child struggling with addiction caused us to withdraw rather than seek help. We learned how to live life with the truth hidden in the back of our hearts." - Darlene, mother who lost son to overdose.

Recovery from SUDs means different things to different people. Broadly speaking, it is a process of change through which people improve their health and well-being while abstaining from or lessening their substance use or by switching to less risky drug use. For some, this may mean complete abstinence; for others, recovery could be ceasing problematic drug use, developing effective coping strategies, improving physical and mental health, or experiencing some combination of those or other outcomes. 

Recognizing that there are potentially many 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. The HEALing Communities Study is implementing training for peer recovery support and enhancing linkages to recovery support services (see callout box, “Testing and Implementing Evidence-Based Strategies in Diverse Settings”). In addition to developing effective recovery strategies, it is necessary to address stigma, racial inequities, housing instability, legal system barriers, and other barriers that keep people with SUDs from receiving the ancillary services 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 beyond abstinence and reduced drug use, 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 stigma and other social determinants of health on recovery.