Nora's Blog

Reflecting on NIDA’s 50th year and looking to 2025

By Dr. Nora Volkow
A child points excitedly out of an airport window onto the airfield while being held by an attentive father, both sharing a moment of discovery.

This past year, NIDA commemorated its 50th anniversary, which made me reflect on how far addiction science has come in a half century—from the barest beginnings of an understanding of how drugs work in the brain, and only a few treatment and prevention tools, to a robustly developed science and multiple opportunities to translate that science into clinical practice. Yet the challenges we face around drug use and addiction have never been greater, with annual deaths from overdose that have vastly exceeded anything seen in previous eras and the proliferation of increasingly more potent addictive drugs.

Our 50th year brought hope, as we finally saw evidence of a sustained downturn in drug overdose deaths. From July 2023 to July 2024, the number of fatal overdoses dropped nearly 17 percent, from over 113,000 to 94,000. We still don’t know all the factors contributing to this reversal, so investigating the drivers of this decline will be crucial for sustaining and accelerating the downturn. We also need to recognize that the decline is not homogenous across populations: Black and American Indian/Alaskan Native persons continue to die at increased rates. And 94,000 people dying of overdose in a year is still 94,000 too many. 

As we begin a new year, I see four major areas deserving special focus for our efforts: preventing drug use and addiction, preventing overdose, increasing access to effective addiction treatments, and leveraging new technologies to help advance substance use disorder (SUD) treatment and the science of drug use and addiction.

Preventing drug use and addiction

The brain undergoes continuous development from the prenatal period through young adulthood, and substance exposures and myriad other environmental exposures can influence that development. Prenatal drug exposure can lead to learning and behavioral difficulties and raise the risk of later substance use. Adverse childhood experiences, including neglect, abuse, and the impacts of poverty, as well as childhood mental disorders, can negatively impact brain development in ways that make an individual more vulnerable for drug use and addiction. Early drug experimentation in adolescence is also associated with greater risk of developing an SUD. 

Early intervention in emerging psychiatric disorders as well as prevention interventions aimed at decreasing risk factors and enhancing protective factors can reduce initiation of drug use and improve a host of mental health outcomes. Research on prevention interventions has shown that mitigating the impact of socioeconomic disadvantage counteracts the effects of poverty on brain development,1 and some studies have even documented evidence of intergenerational benefits, improving outcomes for the children of the children who received the intervention.2 Studies have also shown them to be enormously cost-effective by reducing later costs to healthcare and other services, providing health and economic benefits to communities that put them in place.3 

Yet, in the United States, efforts to prevent substance use have been largely fragmented, and the infrastructure and funding required to bring effective programs to scale is lacking. What kinds of policy innovations could we put into place to ensure that everyone who could benefit from evidence-based prevention services has access to them, whether through school, healthcare, justice, or community settings?  NIDA, along with other NIH Institutes, the Centers for Disease Control and Prevention, and the Substance Abuse and Mental Health Services Administration, have charged the National Academy of Sciences, Engineering, and Medicine with creating an actionable blueprint for supporting the implementation of prevention interventions that promote behavioral health. The report is due out early this year and has the potential for tremendous public health impact.4

Preventing overdose

We also need to continue research toward mitigating fatal overdoses. Comprehensive data on overdose reversals do not currently exist, but recipients of SAMHSA State Opioid Response grants alone reported more than 92 thousand overdose reversals with naloxone in the year ending March 31, 2023, and this is likely just a small fraction of the lives saved. We do not yet know the extent to which greater use of naloxone has played a role in the recent declines in overdose fatalities, but this medication, the first intranasal formulation of which was developed by NIDA in partnership with Adapt Pharma, is a real public health success.

NIDA is supporting research to evaluate approaches to naloxone distribution, for instance through mobile vans and peer-run community services that also provide sterile injection equipment to prevent HIV and HCV transmission. We are also supporting research on new approaches to reversing drug overdoses, such as wearable devices that would auto-inject naloxone when an overdose is detected and electrical stimulation of the phrenic nerve to restore breathing, a method already used in resuscitation devices.5 We are also supporting research on compounds that could potentially reverse methamphetamine overdoses, such as monoclonal antibodies and molecules called sequestrants that bind and encapsulate methamphetamine in the body.6 

Improving access to addiction treatment

In 2023, only 14.6 percent of people with an SUD received treatment, and only 18 percent of people with an opioid use disorder (OUD) received medication.7 Stigma, along with inadequate coverage of addiction treatment by both public and private insurers, contributes to this gap. To fix this will require partnering with payors to develop and evaluate new models for incentivizing the provision of evidence-based SUD care. 

Increased access to methadone is a particularly high priority in the era of fentanyl and other potent synthetic opioids. Results from a recent study in British Columbia showed that risk of leaving treatment was lower for methadone than for buprenorphine. Risk of dying was similarly low for both groups.8 Currently in the United States, methadone is only available from specialized opioid treatment centers, but studies piloting access through pharmacies have shown promise.

OUD medications also need to be accessible to people with SUD in jails and prisons. Research conducted in justice settings has shown that providing access to all three FDA-approved medications for OUD during incarceration reduced fatal overdose risk after release by nearly 32 percent.9 Access to buprenorphine during incarceration was also associated with a 32 percent reduction in recidivism risk.10 Through NIDA’s  Justice Community Overdose Innovation Network (JCOIN), we continue to promote research into innovative models and strategies for integrating medications for OUD in justice settings.

I am also hopeful that we will soon see increased utilization of contingency management for treating stimulant use disorders. Providing incentives for treatment participation and negative drug tests is the most effective treatment we have for methamphetamine and cocaine addictions, but implementation has been hindered by regulatory ambiguities around caps on the dollar value of those incentives. However, demonstration projects underway in four states (California, Washington, Montana, and Delaware) are implementing contingency management with higher incentives and could further bolster evidence for the effectiveness—including cost effectiveness—of this approach.

Leveraging new treatments and technologies

There are many promising new technologies that could transform the treatment of addiction, including central and peripheral neuromodulation approaches. Transcranial magnetic stimulation (TMS) was already approved by the FDA as an adjunct treatment for smoking cessation and peripheral auricular nerve stimulation was approved for the treatment of acute opioid withdrawal. TMS, transcranial direct current stimulation (tDCS), and peripheral vagal nerve stimulation are under investigation for treating other SUDs. Low-intensity focused ultrasound—a non-invasive method that can reach targets deep in the brain—is also showing promise for the treatment of SUD. NIDA is currently funding clinical trials to determine its safety and preliminary efficacy for treating cocaine use disorder11 and OUD with or without co-occurring pain.12 

Advances in pharmacology have helped identify multiple new targets for treating addiction that are not limited to a specific SUDs like OUD. Instead, these targets aim to modulate brain circuits that are common across addictions; they include among many others D3 receptor partial agonists/antagonists, orexin antagonists and glucagon-like peptide 1 (GLP-1) agonists. The latter are particularly promising, as these types of drugs, including semaglutide and tirzepatide, are already being used for the treatment of diabetes and obesity. 

Anecdotally, patients taking GLP-1 agonists report less interest in drinking, smoking, or consuming other drugs. Recent studies based on electronic health records have revealed that people with SUDs taking GLP-1 medications to treat their obesity or diabetes had improved outcomes associated with their addiction, such as reduced incidence and recurrence of alcohol use disorder,13 reduced health consequences of smoking,14 and reduced opioid overdose risk.15 NIDA is currently funding randomized clinical studies to assess the efficacy of GLP-1 agonists for the treatment of opioid and stimulant use disorders and for smoking cessation. 

Creation of large data sources and repositories in parallel with advances in computation and analytical modeling including AI are helping in the design of new therapeutics based on the 3D molecular structure of addictive drugs and the receptors they interact with.16 NIDA-funded researchers have published studies showing that AI could be used to provide more timely, comprehensive data on overdose, such as by using social-media to predict overdose deaths.17 It could be used to enable higher-resolution analyses in basic neuroscience research18 and facilitate studies using large data sources like electronic health records.19 AI is also being used to support delivery of behavioral therapies and relapse prevention in virtual chatbots and is being studied in wearable devices. Although there is much work to be done to ensure that AI is deployed safely and ethically, particularly in clinical settings, this technology has considerable potential to enhance and expand access to care.

AI will also be transformative for analyzing big data sets like those being generated by the Adolescent Brain Cognitive DevelopmentSM (ABCD) Study and HEALthy Brain and Child Development Study. These landmark NIH-funded studies are gathering vast quantities of neuroimaging, biometric, psychometric, and other data across the first two decades of life. They will be able to answer important questions about the impacts of drugs and other environmental exposures on the developing brain, inform prevention and treatment interventions, and establish a valuable—and unprecedented—baseline of neurodevelopment that will be a crucial resource in pediatric neurology. 

The field of addiction science has progressed at a breathtaking pace. These advances could not have been made without the commitment of an interconnected community of people. Researchers, clinicians, policymakers, community groups, and people living with SUDs and the families that support them all play a role in collaboratively finding solutions to some of the most challenging questions in substance use and addiction research. Together, we turn our eye to 2025 and the challenges and opportunities ahead. 

References
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