2016-2020 NIDA Strategic Plan
Goal 3: Develop New and Improved Treatments

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GOAL 3: Develop new and improved treatments to help people with substance use disorders achieve and maintain a meaningful and sustained recovery

The last few decades have seen dramatic advances in our understanding of the biology of addiction, but the range of treatment options available for most substance use disorders (SUDs) remains limited. Pharmacotherapies approved by the U.S. Food and Drug Administration (FDA) exist for dependence on opioids (i.e., methadone, buprenorphine, and extended-release naltrexone), alcohol, and nicotine, and evidence-based psychosocial treatments (e.g., cognitive behavioral therapy, contingency management, etc.) are available for these and other SUDs91,92, but the efficacy of these treatments is far from ideal. There is a clear need to develop better treatment strategies that target the biological substrates of addiction across stages, including detoxification, recovery maintenance, and relapse prevention.

SUDs are chronic conditions that often require long-term management. The chronic nature of the disorder means that relapsing is common, with recurrence rates similar to those for other well-characterized chronic medical illnesses that have both physiological and behavioral components—such as diabetes, hypertension, and asthma.93 SUDs can be managed successfully in many cases, but available treatments are ineffective for others. In addition, the vast majority of individuals who have SUDs never seek treatment.1

There are many new approaches that show promise for the treatment of SUDs in preclinical studies including novel pharmacotherapies, behavioral therapies, vaccines, biofeedback, and direct manipulation of brain activity via transcranial magnetic stimulation (TMS) and electrical deep brain stimulation.94–98 Translating these promising interventions into clinical practice will require testing their efficacy in target populations in clinical trials. However, a key challenge in this area is the reticence of pharmaceutical companies to invest in developing treatments for addiction. This is due in part to the perception that the market for such treatments is small and in part to difficulties conducting clinical trials in patients with multiple comorbidities. In addition, the only end point currently accepted by the FDA for clinical trials examining therapeutics for SUDs is abstinence. This represents a particularly high bar, which discourages investment by the private sector.99 NIDA, together with the FDA and our academic and industrial partners, is working towards validating end points other than abstinence, and this will remain a strategic priority over the next 5 years.

Targeting the Brain’s Circuits to Treat SUDs: Transcranial Magnetic Stimulation

All mental and behavioral phenomena—whether healthy or disordered—result from electric currents coursing through neural circuits in the brain. Thus, it should be possible, at least in theory, to disrupt and perhaps even correct a disease process by activating or inhibiting specific brain circuits.

TMS, first developed in 1985, uses localized magnetic pulses to activate targeted regions of the brain. In October 2008, the FDA approved TMS as a noninvasive method of brain stimulation for treatment of major depression among patients who do not respond to at least one antidepressant medication. TMS is also being studied as a treatment for many other neuropsychiatric disorders.

Fortunately, we now have an increased understanding of the brain circuits that become disordered in individuals with SUDs. These include circuits governing impulse control, motivation, reward-dependent learning, and emotional processing. Growing evidence suggests that TMS may be helpful in the treatment of SUDs, particularly if the pulses are administered in rapid succession. This technique, referred to as repetitive TMS (rTMS), enables longer-lasting changes in brain activity. For example, two of four controlled clinical trials using rTMS to reduce nicotine craving found decreased cigarette smoking, and a trial in cocaine users found decreased cocaine use after treatment.100

We still have much more to learn about how to optimize rTMS treatment: what its duration should be, whether it can reduce cue-induced craving, and whether it can be combined with other treatments. We also still do not fully understand how rTMS achieves its effects in treating SUDs, so it is still considered experimental. As we learn more about brain circuit changes in the brains of addicted individuals, it could turn out to be a promising noninvasive and nonpharmacological treatment approach.

The ongoing transformation of the health care system also presents significant opportunities for advancing treatment for SUDs. Health reform initiatives are promoting the integration of behavioral health care into general health services. In addition, new payment models—including shared savings programs and the hospital readmission penalty—are creating financial incentives for addressing broader issues, including SUDs, that contribute to treatment success and long-term outcomes. Medical costs for treating patients with chronic physical health conditions can be two to three times higher in patients with comorbid behavioral health disorders101, and untreated SUDs are associated with poorer adherence to treatment plans and medications, leading to worse outcomes.102 However, less than 12 percent of people with SUDs receive treatment, and only a fraction of those receive care that is adequate, making addressing SUDs a prime target for reducing health care costs.1 Research can help to define how best to prevent substance use, identify individuals with problematic substance use or SUDs, and engage patients in appropriate treatment in general health care and integrated care settings.

Another element of the changing health care landscape that has the power to affect SUD treatment is the rapid development and adoption of technologies including electronic health records, telehealth, and mobile health technologies. These technologies have the power to revolutionize health services research and to drive new treatment delivery models by supporting more effective integration of care, extending the reach of the SUD treatment workforce, enabling real-time patient monitoring and support, delivering technology-based intervention, and engaging patients who are hesitant to participate in the traditional behavioral health treatment system. Research is needed to inform how best to leverage these new technologies to improve patient outcomes.

Ongoing reform efforts within the criminal justice system also present new opportunities for improving SUD treatment. It is estimated that one half of all prisoners meet the diagnostic criteria for drug abuse or dependence, yet less than 20 percent of prisoners with drug abuse or dependence receive treatment while incarcerated.103 Left untreated, drug-addicted offenders often relapse to drug use and return to criminal behavior. This represents a significant opportunity to intervene with a high-risk population. More research is needed to develop improved prevention and treatment models within the criminal justice system that fit the chronic nature of SUDs and ensure a continuity of treatment services upon community reentry. In addition, integrated implementation strategies are needed not only to incorporate the best criminal justice practices and therapeutic services, but also to use the best organizational practices to deliver them.

A primary goal of NIDA research is the amelioration of the health burden caused by addiction; the development of effective interventions is vital to the realization of this goal. To facilitate the development of innovative intervention strategies, NIDA will support research to:

Juvenile Justice: A Key Intervention Point

Drug use and involvement with the criminal and juvenile justice systems go hand in hand, and the number of incarcerated drug offenders continues to grow. There are many competing theories about how to best address this persistent and costly phenomenon, but the scientific understanding of addiction as a brain disorder should help us see that punishment alone cannot be effective at addressing SUDs. Instituting effective treatment programs for offenders whose criminal behavior is directly related to drug use is urgently needed as part of a humane and comprehensive public health and safety intervention. This rationale only strengthens when we consider that incarceration provides a unique opportunity to reach those who would otherwise not seek treatment.

NIDA funds a broad portfolio of research addressing adult SUD issues within the criminal justice system, but the ethical case for robust treatment options is particularly compelling when it comes to incarcerated adolescents. About half of all teens who enter the juvenile justice system need treatment for SUDs, and the remaining half would no doubt benefit from a drug use prevention intervention.104 While effective interventions exist for youth with substance use problems in general, the juvenile justice system has been slow to embrace evidence-based principles and practices; service delivery is typically inconsistent and continuity of care following release into the community remains a serious challenge.

To begin addressing these critical needs, NIDA has spearheaded the Juvenile Justice Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS), a $22.5 million, 5-year cooperative study designed to support research on the implementation of services to improve the continuum of SUD and HIV prevention and treatment interventions for youth under juvenile justice supervision. Collectively, the cooperative includes three key components: (1) a set of integrated, large-scale implementation research studies; (2) a large-scale national survey; and (3) two pilot implementation studies.

These complementary efforts are aimed at increasing the capacity of the juvenile justice system to address youth substance use. The large-scale implementation study is a randomized controlled trial designed to identify the most effective strategies to promote adoption of evidence-based prevention and treatment interventions in 36 juvenile justice systems across the country. The JJ-TRIALS survey is a tool for measuring the degree to which evidence-based practices are used throughout the U.S. juvenile justice system. Lastly, JJ-TRIALS pilot implementation studies will examine how well the strategies identified in the large-scale implementation study generalize to juvenile justice partnerships in other service sectors (e.g., public health departments to target HIV, the education system to target prevention services).

This initiative has the potential to enhance the implementation of SUD treatment in a context where youth engage multiple systems that must collaborate to ensure their complex needs are met. The JJ-TRIALS could become the foundation for future work exploring important questions about other systems affecting juvenile care, like coordinating treatment for co-occurring mental and SUDs, addressing family-level needs, and better utilizing technology and other system infrastructure in facilitating coordination among service providers.