It is an important time for addiction science. The opioid crisis continues to claim tens of thousands of American lives as well as contribute to the spread of infectious disease. And, after the election this past November, most Americans now live in a state where marijuana is legal either for adult recreational use or for therapeutic use, and the effects of this drug’s wider availability on public health demand scientific study. The need for better substance use disorder treatments, better diagnostic methods, and better prevention strategies has never been greater. The beginning of a new year gives us an opportunity to take stock of all we have recently accomplished toward meeting these scientific goals, as well as to set our sights on the challenges facing us ahead.
Given the unique vulnerability of the developing brain to substance use and its many life and health consequences, NIDA retains a strong focus on adolescence. 2016 brought the launch of the Adolescent Brain Cognitive Development (ABCD) study in partnership with the National Institute on Alcohol Abuse and Alcoholism, the National Cancer Institute, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the Office of Behavioral and Social Sciences Research, the National Institute of Child Health and Human Development, and the National Institute on Minority Health and Health Disparities. This landmark, 10-year longitudinal study will explore how adolescent behaviors including substance use impact brain structure and function and is now recruiting participants at 21 research centers nationwide. 2016 also brought some good news about adolescent substance use: The annual Monitoring the Future survey showed declines in the use of nearly all substances across all grades. The only exception was marijuana, which declined in the younger grades but has held steady for several years among 12th graders despite increasing use among adults and diminishing perceptions of the drug’s harms by all age groups.
In 2016, NIDA achieved several milestones that will aid in the fight against the opioid overdose epidemic. In February, Nasal Narcan, an intranasal naloxone formulation that can immediately restore normal breathing in a person overdosing on prescription opioids or heroin and thus save their life, became available. This formulation was developed through a NIDA partnership with Lightlake Therapeutics, Inc. (a partner of Adapt Pharma Limited). And in May, the buprenorphine implant, Probuphine, for which NIDA funded early trials, was approved by the FDA. The implant provides sustained therapeutic levels of buprenorphine for 6 months, potentially improving treatment adherence and reducing the potential for diversion.
Also last year, NIDA-funded research at Yale School of Medicine revealed the benefits of starting opioid-addicted emergency department patients on buprenorphine immediately (as opposed to referring them to treatment). Initiating treatment in emergency departments during a moment of crisis increases treatment engagement, and could potentially reduce relapse risk while waiting for treatment if all that is offered is a referral. Another study found that initiating extended-release naltrexone in opioid-addicted prison inmates reduced their relapse rate compared to brief counseling and referral to community treatment.
In 2016, NIDA also partnered with the Appalachian Regional Commission (ARC) to fund epidemiological research into injection opioid use that could lead to improved interventions in an economically distressed part of the country that has been hit especially hard by the opioid crisis. NIDA, ARC, the Centers for Disease Control and Prevention, and the Substance Abuse and Mental Health Services Administration offered additional funding to support work with state and local communities in developing best practices for responding to opioid injection epidemics in rural communities.
At the root of the opioid crisis is the overuse of opioids to treat pain. Lessening our use of these drugs comes with an enormous responsibility to find new pain treatments that are effective but pose a lower risk for misuse, addiction, and overdose. Recently NIDA-funded researchers at Wake Forest University reported findings on a novel opioid analgesic, BU08028, that lacked abuse liability in primates—a possible first step toward safer pain medications.
But as part of the goal to improve pain treatment, we also need new, objective ways to assess pain that would enable us to identify subpopulations whose pain has distinct causes. To that end, NIDA has been investing in research to develop new biomarkers, including neuroimaging biomarkers, which could not only improve our ability to diagnose pain, but also clarify the underlying neuropathology. NIDA-funded research at the University of Colorado is working to develop an fMRI-based signature of physical pain, which could potentially help researchers identify novel treatment targets.
In 2016, NIDA also continued to advance basic research on the neurobiological and psychosocial underpinnings of substance use disorders. New technologies enabling researchers to trace relationships between input and output (or TRIO) are giving us greater understanding of reward circuits and how information flows through them. Other recent research has identified competing brain circuits that control the transition between goal-directed and habitual behaviors. A deeper understanding of the brain circuits that mediate addiction-related behaviors is helping researchers to identify new targets for prevention and treatment that address the specific neurobiological drivers of risk for substance use disorders and the loss of control in addiction.
NIDA-funded studies from 2016 also advanced our understanding of the structure of receptors that mediate the rewarding properties of drugs—including the Cannabinoid type 1 (CB1) receptor, the mu opioid receptor, and the alpha 4 and beta 2 nicotinic receptors. This research could provide the foundation for new medications for pain and addiction. Our research is also paving the way toward better understanding of the role played in various brain disorders by epigenetic processes—which produce stable, potentially heritable changes in gene expression without altering the sequence of DNA. For example, NIDA-funded researchers at Harvard Medical School for the first time used PET imaging to characterize an epigenetic marker (histone deacetylase) in the healthy human brain. This will illuminate the role of epigenetics in addiction and recovery, including that of transgenerational inheritance of addiction risk.
New treatments are not limited to traditional pharmacotherapies. NIDA is continuing to fund research on the development of vaccines and other compounds that recruit the body’s own immunologic defenses against drugs, as well as non-drug approaches like transcranial magnetic stimulation (TMS), deep-brain stimulation, and neurofeedback. Last year our intramural research program, in collaboration with Italian researchers, reported positive findings that TMS reduced cocaine use and cocaine cravings in patients with cocaine addiction. Follow-up studies will examine the use of this technology in treating pain and addiction to opioids and nicotine. NIDA also continues to fund investigation of existing medications that could be repurposed for addiction treatment—which would shorten the pathway to FDA approval. This includes a clinical trial on lorcaserine, an FDA-approved medication for obesity, for the treatment of cocaine use disorder.
This just scratches the surface of what NIDA has been doing to ensure that science drives the solutions to drug misuse and addiction. In 2017, we will continue our hard work in addressing the opioid epidemic both by developing new pain and addiction treatment strategies and by improving the delivery of evidence-based treatments through implementation science. We will continue to intensively study the consequences of changing marijuana policies around the country to better understand how to minimize the public health consequences of greater marijuana availability. In parallel, we will continue our commitment to basic science research, which gives us the fundamental knowledge with which to develop solutions to address the problems associated with drugs and addiction.