As of 2014, nearly 27 million Americans were current users of illicit drugs, and almost 67 million Americans were current users of tobacco products.1 Drug use and substance use disorders (SUDs) represent major public health problems that affect millions and place enormous burdens on society. The accumulated costs to the individual, the family, and the community are staggering and arise as a consequence of many direct and indirect effects, including compromised physical and mental health, loss of productivity, reduced quality of life, increased crime and violence, abuse and neglect of children, and health care costs. The combined yearly economic impact of these factors is estimated at $193 billion for illicit drug use and $295 billion for tobacco use.3,4
The profound complexity of human behavior and of behavioral disorders like SUDs requires a deeper understanding of the fundamental processes that give rise to them. How do biological and environmental mechanisms influence behavior, and how does the disruption of these mechanisms lead to addiction? A more detailed understanding of the links between genes, brain structure and function, and behavior—in both health and disease—will lead to more personalized and precise interventions to prevent and treat addiction. For example, we now have an unprecedented capacity to screen for thousands of genetic variations and catalog how they affect addiction risk by influencing brain maturation and architecture, brain circuit function, and behavioral patterns.5 NIDA-supported researchers are using whole-genome sequence analysis to identify genes that modulate addiction risk and exploring how environmental factors—such as early-life stress and peer influences—can affect the expression of those genes (via epigenetic modifications) to either increase or decrease risk across the lifespan and across different stages of the addiction trajectory.
Stunning technological advances, particularly in the field of neuroscience, are allowing scientists to ask questions that were unimaginable only a few years ago. Ever more powerful tools in neuroimaging, transgenics, opto- and chemogenetics, molecular modeling, and bioinformatics are supporting the systematic identification of genetic, environmental, and neural circuit variables that influence an individual’s risk for drug use and addiction. For example, clustered regularly interspaced short palindromic repeats (CRISPR), a powerful new gene editing technology, is poised to revolutionize biomedical research.6 This technology is inexpensive, fast, and easy to use and has rapidly been adopted by researchers across the country to understand the role of specific genetic variations in complex processes including addiction. This research will improve our overall understanding of the various phases of addiction and identify targets for new therapies that could ultimately revolutionize our prevention, diagnosis, and treatment capabilities. It will also inform our understanding of the role of genetics in the susceptibility to adverse medical consequences associated with drug use.
Recent advances in clinical technologies are also presenting new opportunities for research. Technologies that can target and modulate brain activity, including transcranial magnetic and electrical stimulation and electric deep brain stimulation, as well as neurofeedback techniques are being explored to translate new knowledge about the underlying neurobiology of addiction into novel diagnostic techniques and personalized therapeutic approaches.
NIDA is also committed to harnessing recent advances in health care technologies. Recent federal efforts7 have led to a rapid increase in the adoption of electronic health records by health care providers and spurred advances in other health information technologies, including telehealth and mobile health applications. These technologies have the potential to revolutionize behavioral health care and related research. The synergistic implementation and deployment of these technologies with Big Data mining will allow researchers to draw on unprecedented amounts of health information, transforming our understanding of how individual-level factors contribute to health and disease and ushering in a new era of personalized medicine. It will also provide a better understanding of how substance use and SUDs influence outcomes for diverse health conditions.
To understand the causes and trajectories of SUDs, it is critical to investigate the biological, medical, social, and economic factors that contribute to them. NIDA strives to translate the returns of its investments in genetics, epigenetics, neuroscience, pharmacotherapy, behavioral science, and health services research into the most effective strategies for preventing and treating substance use and addiction. In addition to advancing basic and clinical sciences related to drug use and its consequences, NIDA prioritizes research efforts relevant to current public health challenges, such as:
- the opioid overdose epidemic
- changes in state marijuana laws
- implementation of evidence-based SUD interventions
- emerging drugs and new delivery systems
- spread of infectious disease
In recent years, the interrelated problems of prescription opioid misuse and heroin use have awakened high levels of public health awareness and concern, demanding a robust, evidence-based, and multifaceted response. An estimated 1.9 million people in the United States suffered from SUDs related to prescription opioid pain medications in 2014, and 586,000 suffered from a heroin use disorder.1 These high rates of opioid use disorders are accompanied by devastating medical and social consequences, including deaths from overdose, a rising incidence of neonatal abstinence syndrome in newborns due to maternal opioid use during pregnancy, and increased spread of infectious diseases such as HIV and hepatitis C (HCV) due to sharing of needles for injection drug use and increased risky sexual behaviors.8–11
Research has demonstrated the efficacy of multiple types of interventions, including behavioral prevention interventions12; monitoring and risk reduction through prescription drug monitoring programs13–16; programs to provide overdose education and distribute the overdose-reversal drug naloxone to opioid users and potential bystanders9,17,18; drug courts in lieu of incarceration to increase access to treatment19; pharmacological treatments including methadone, buprenorphine, and extended-release naltrexone, combined with behavioral interventions20–23; and abuse-deterrent formulations for opioid pain relievers.24,25 NIDA will continue its close collaborations with other NIH institutes and private industry partners to develop analgesics with reduced abuse potential and to identify biomarkers of pain severity that can be used to evaluate new treatments and further personalized interventions. Similarly, NIDA will continue its partnership with other federal agencies and communities in addressing the challenges posed by abuse of prescription opioids and heroin in this country.
Saving Lives: Intranasal Naloxone
Deaths from opioid overdoses (prescription pain relievers and heroin) have skyrocketed since 1999, leading the U.S. Department of Health and Human Services to deem the trend an epidemic and prompting widespread federal, state, and local actions. We can attack the epidemic on several fronts, including reducing the diversion of prescription drugs, making effective medical treatments more available to people who are addicted, and creating new ways to treat pain that do not involve addictive opioid compounds. But another crucial way we can combat the epidemic of deaths from opioids is with naloxone, a medication that reverses an opioid overdose. Naloxone can quickly restore normal breathing to a person in danger of dying from an opioid overdose.
Naloxone is already carried by emergency medical personnel and other first responders. But by the time an overdosing person is reached and treated, it is often too late to save him or her. To solve this problem, several experimental Overdose Education and Naloxone Distribution (OEND) programs have given naloxone directly to opioid users, their friends or loved ones, and other potential bystanders, along with brief training on how to use this medication. These programs have been shown to be a very effective, as well as cost-effective, way of saving lives.18,26,27
Until recently, only injected forms of naloxone were approved by the U.S. Food and Drug Administration (FDA), but many OEND programs use syringes fitted with an atomizer so the drug can be sprayed into the nose. Because the drug is not designed to be given this way, the dose and other properties of the medicine may not be optimal. However, in November 2015, the FDA approved a user-friendly intranasal formulation of naloxone, Narcan® nasal spray, that matches the injectable version in terms of how much of the drug gets into the body and how rapidly. The development of Narcan® nasal spray was supported by NIDA through a public-private partnership with Lightlake Therapeutics, Inc. and Adapt Pharma.
According to the Centers for Disease Control and Prevention, more than 74 Americans die each day from an overdose involving prescription pain relievers or heroin.28 If we are to reverse these trends, we need to do all we can to ensure that emergency personnel, as well as at-risk opioid users and their loved ones, have access to life-saving tools like intranasal naloxone.
Marijuana is the most commonly used illicit drug in the United States, with more than 22 million people (8.4 percent) over the age of 11 reporting use in the past month.1 In light of rapidly shifting state policies regarding marijuana use for medical and recreational purposes, it is more important than ever to produce and disseminate accurate information about marijuana’s health effects and potential therapeutic uses and to conduct the research needed to fill the gaps in our knowledge.
Regular use of marijuana among adolescents is correlated with detrimental changes in the developing brain and negative social and behavioral outcomes29; however, it is currently unclear how changes in local, state, and national policies will impact—and will be impacted by—adolescent use and related outcomes, particularly during the most formative years of learning and development. There are many open questions related to marijuana legalization that research can help to address, including how policy changes will affect:
- use of marijuana and related health outcomes, including mental illness
- health outcomes—positive and negative—related to medical marijuana use
- usage patterns of other drugs, alcohol, and tobacco
- public safety outcomes related to drugged driving, crime, etc.
- potency and cannabinoid content of commonly consumed strains
- new routes of administration (e.g., vaping, dabbing, edibles)
- societal norms and perceptions
In addition, more research is needed to develop prevention interventions that target marijuana use among youth in the context of changing norms, to understand the health consequences related to the increasing potency of marijuana, to characterize the consequences of marijuana use on the developing brain, and to develop new treatment strategies for cannabis use disorders. NIDA-supported science aims to address these gaps and to help inform decision-making related to state and federal marijuana policies. In addition, in line with NIDA’s mission of reducing the burden of drug use and SUDs, ongoing research will continue to explore the therapeutic potential of marijuana-derived compounds for pain and addiction.
Addiction is a complex but treatable disorder that affects brain function and behavior. Unfortunately, we have a significant and ongoing treatment gap in our nation. Among those who need treatment for an SUD, few receive it. In 2014, 22.5 million Americans needed treatment for an SUD, but less than 12 percent received treatment at a specialty substance abuse facility.1 Further, many specialty treatment programs do not provide current evidence-based treatments—less than 50 percent provide access to medication-assisted treatment for opioid use disorders.30 In addition, it is clear that preventing drug use before it begins—particularly among young people—is the most cost-effective way to reduce drug use and its consequences.31 However, evidence-based prevention interventions also remain highly underutilized.
NIDA is committed to reducing these gaps using a multipronged approach including health services and implementation research to develop and test strategies to:
- Facilitate the dissemination and sustainable adoption of evidence-based treatments for SUDs in diverse health care settings including primary care and the criminal justice system
- Increase access to evidence-based treatments including pharmacotherapies and behavioral interventions for SUDs
- Identify individuals with problematic drug use and connect them to appropriate care
- Address stigma and discrimination to encourage people to seek treatment
- Facilitate the dissemination and sustainable adoption of evidence-based prevention interventions, including both targeted and community-based interventions, in diverse settings including communities, schools, health care, and criminal justice
NIDA works with diverse stakeholders to raise awareness about the value of addiction prevention and treatment interventions and to encourage people with problematic drug use to seek care. Our NIDAMED initative and Blending Initiative develop medical education courses and materials to train clinicians on evidence-based practices related to prescribing for pain, on identifying individuals with risky substance use, and on treating adolescents with SUDs. In addition, NIDA, through the NIH Pain Consortium, helps to fund 11 Centers of Excellence in Pain Education that act as hubs for the development, evaluation, and distribution of pain management curriculum resources for medical, dental, nursing, and pharmacy schools.
NIDA monitors and investigates emerging threats to public health stemming from new patterns of drug use. One current trend of concern is the increasing use of synthetic drugs, including synthetic cannabinoids (e.g., K2, herbal incense), synthetic cathinones (e.g., bath salts, Flakka), and synthetic hallucinogens (e.g., 2-C, NBOME). Recent surges in calls to poison control centers, hospitalizations, and deaths linked to consumption of synthetic drugs have prompted concern across the country.32 Basic research is needed to better understand the pharmacology and health effects of these synthetic drugs, sociocultural factors that influence their use, and effective strategies for prevention and treatment.
Another trend that NIDA researchers are watching closely is the rising popularity of e-cigarettes and vaporizer (vape) pens. E-cigarettes are often promoted as safer alternatives to traditional cigarettes, which deliver nicotine by burning tobacco, but little is actually known about the neurobiological consequences and health risks of using these devices. While they do not produce tobacco smoke, e-cigarettes often contain nicotine—a highly addictive drug—along with other potentially harmful chemicals and additives, such as formaldehyde, acetaldehyde, and toxic metals.33 E-cigarettes are increasingly popular among adolescents, a population that is particularly vulnerable to the addictive power of nicotine and other drugs. A recent study found that adolescent e-cigarette users are significantly more likely to begin smoking conventional cigarettes compared to those who have not used e-cigarettes.34 NIDA is also concerned about the use of these devices for administration of other drugs, including high-potency cannabis extracts (hash oil) and synthetic cannabinoids. It is not yet clear how use of these devices will affect risk for addiction or other adverse health effects.
Between January and August 2015, a rural community of 4,200 residents in southern Indiana saw the emergence of 184 people newly infected with HIV35, 95 percent of whom were co-infected with HCV. This outbreak was driven primarily by injection of the opioid medication oxymorphone.8 This highlights that injection drug users cannot be ignored in the efforts to achieve an AIDS-free generation and eliminate HCV. Even in the United States, where significant progress had been made in reducing the number of new HIV infections attributable to injection drug use (IDU)36, the latest report coming out of Indiana highlights the challenges that IDU presents in tackling the intertwined HIV and HCV crises. Effective, evidence-based strategies exist for preventing the spread of HIV and other infectious diseases among drug-using populations. This includes the use of antiretroviral therapy as prevention for HIV transmission—a strategy known as Seek, Test, Treat, and Retain37—combined with treatment for opioid use disorders with medication-assisted treatment to improve compliance with antiretroviral treatment.38 However, implementation of these treatment strategies among substance users has been slow, highlighting the need for new research to scale up efforts in this area. In addition, basic research is still needed to develop approaches to identify and eliminate HIV reservoirs and latent virus and to understand how drugs of abuse affect them. Unlike HIV, HCV can be cured39; however, new research is needed to identify effective models for linking comorbid HIV- and HCV-positive drug users to appropriate care and improving their treatment retention and outcomes.
When making tough decisions about how to spend precious research dollars, institutions often naturally lean toward projects with a reasonable chance of success and shy away from more risky proposals. But the fact is that some of the biggest research payoffs may actually flow from out-of-the-box, untested, high-risk ideas. To capture those ideas, we need to be creative and flexible in our funding mechanisms.
The NIDA Avant-Garde Award Program for HIV/AIDS and Drug Use Research is one such mechanism. It was created to support highly innovative investigators with groundbreaking ideas that are likely to open new areas of research on the prevention and treatment of HIV/AIDS among drug users. Although it is open to investigators at all career stages, the Avant-Garde Award has not attracted many in the early stages of their careers who may not have the data needed for an NIH Research Project Grant (R01). This deficit called for some programmatic tweaking, which led to NIDA’s creation of two Avenir (meaning "future" in French) Award Programs: the Avenir Award Program for Research on Substance Abuse and HIV/AIDS and the Avenir Award Program for Genetics or Epigenetics of Substance Abuse. These programs complement Avant-Garde by focusing on exceptionally creative early-stage investigators who propose trailblazing—and possibly transformative—approaches to these two major problem areas in biomedical and behavioral research.
The Avenir Award Program for Research on Substance Abuse and HIV/AIDS (DP2) supports highly innovative research aimed at improving prevention and treatment, long-term retention in care, and ultimately, eradication of HIV within at-risk, substance-using populations. In 2015, NIDA funded four new Avenir Awards for Research on Substance Abuse and HIV/AIDS. These projects will use a wide range of approaches, including:
- Exploring interventions to reduce HIV transmission among people who inject drugs
- Using high-resolution computer modeling to develop community-specific responses to HIV transmission among people who inject drugs
- Examining the potential for a new single-dose antibody therapy to suppress viral replication in HIV-infected people, which would be highly beneficial for substance users who have trouble adhering to current HIV treatments
- Integrating neurobiological and behavioral research techniques to advance our understanding of HIV-related decision-making in drug users
The Avenir Award Program for Genetics or Epigenetics of Substance Abuse (DP2) is funding projects in the following areas:
- Drug-related behaviors and how they alter epigenetic modifications in the brain, to develop more effective epigenetic-based addiction treatment and prevention strategies
- Epigenetic mechanisms underlying nicotine dependence, to provide a foundation for developing new treatments to help people stop smoking
- Development of novel technologies and methods for genetic and epigenetic analysis
- Integration of epigenetics and genetic analyses