As NIDA sets its sights on new goals and objectives for 2020 and beyond, I like to reflect on how far we have come in our research efforts, especially as they concern the opioid crisis, one of the biggest public health issues of our era. Although deaths from synthetic opioids like fentanyl continue to rise, glimmers of hope are starting to appear. Provisional numbers show that overall overdose deaths have held steady rather than increasing since 2018, and a massive federal investment toward finding scientific solutions to the crisis promises to further turn the tide against opioid and other drug use disorders.
The biggest news of the past year is the grant awards in the Helping to End Addiction Long-termSM Initiative, or NIH HEAL InitiativeSM. In Fiscal Year 2019, 375 grants, contracts, supplements, and cooperative agreements totaling $945 million were awarded in 41 states. As part of this aggressive, trans-agency effort, NIDA is funding research on prevention and treatment of opioid use disorder, including developing new treatments and expanding access to those that already exist.
The HEALing Communities Study led by NIDA in close partnership with the Substance Abuse and Mental Health Services Administration is testing the implementation of an integrated array of evidence-based practices in various healthcare, behavioral health, justice, and community settings in 67 hard-hit communities across four states. Objectives of the study include increasing the number of people with OUD receiving medications for their disorder, increasing naloxone distribution to help reverse opioid overdoses, and reducing high-risk opioid prescribing, with the goal of reducing opioid overdose deaths by 40 percent in those communities over of the next three years. Effective strategies learned from this project can then be exported to other communities.
Other HEAL projects are aimed at finding ways to address the prevention and treatment needs of the most at-risk populations. Grants to 12 institutions as part of the Justice Community Opioid Innovation Network (JCOIN) will create a network of researchers in 15 states and Puerto Rico to study ways to scale up and disseminate evidence-based interventions in a population with extremely high rates of OUD and overdoses, including evaluating the use of the different medications for OUD in jails and prisons as well as in parolees suffering from OUD. In a separate set of projects, NIDA is funding research aimed at preventing the transition from opioid use to OUD in young adults, including projects targeting rural and American/Indian communities.
NIH HEAL money has also allowed NIDA to greatly expand our Clinical Trials Network and, in partnership with other Institutes, is additionally partially supporting pilot studies in preparation for a large-scale study of brain health and development across the first decade of life. The HEALthy Brain and Child Development (hBCD) study, along with the already-underway Adolescent Brain and Cognitive Development (ABCD) study (not funded through HEAL), will contribute in innumerable ways to our understanding of brain development and the many factors influencing risk and resilience for substance use during childhood and adolescence.
Basic Science Highlights
In 2019, researchers at NIDA-funded Yale University made significant strides toward understanding biological predictors of addiction and relapse. Using functional magnetic resonance imaging and machine learning, Sarah W. Yip and colleagues found that functional connectivity among a number of brain regions predicted chances of achieving abstinence in patients receiving treatment for cocaine use disorder. Their results, published in the American Journal of Psychiatry last February, could lead to new approaches to treating cocaine addiction by intervening directly in those pathways.
Genetic approaches are also yielding important insights in this area. An analysis of genome-wide association studies (GWAS) published in Nature Genetics last January identified hundreds of gene loci associated with tobacco and alcohol use and related health conditions. Genes involved in dopaminergic, nicotinic, and glutamatergic signaling were among those identified. Another partially NIDA-supported GWAS study published in Nature Neuroscience in July identified an association between expression of the gene for the cholinergic receptor nicotinic α2 subunit with cannabis use disorder in brain tissue from a large Icelandic sample.
NIDA-supported basic science is also shedding important light on opioids and the brain’s opioid signaling systems. Research published in June in ACS Central Science provided new insights while raising new questions about the drug kratom. Its active ingredient mitragynine acts as a weak partial agonist at the mu-opioid receptor (MOR), but new findings by a team that included researchers at Columbia and Memorial Sloan-Kettering found that the drug’s analgesic properties are significantly mediated by a metabolite produced when mitragynine is consumed orally, called 7-hydroxymitragynine. In mice, at least, this compound seems to provide analgesia but with fewer respiratory-depressing and reward-associated side effects than other opioids such as morphine. These findings point toward the potential of this drug in pain research as well as the need for further research on the pharmacology of kratom’s constituents, their toxicity and potential value in the treatment of OUD.
Although the MOR system is most commonly associated with pain and pain relief, other receptors are also involved. One important dimension of pain is the negative affect commonly associated with it, and NIDA-supported research published in Neuron in March found that the kappa-opioid signaling system, specifically in cells located in the shell of the nucleus accumbens, are involved in processing pain-associated negative affect. This discovery could perhaps provide new targets for treating the emotional distress associated with many pain-associated syndromes.
Translating addiction science into new treatments and treatment tools is another area where NIDA is having an impact. For example, in the past few years, NIDA has been extremely successful in winning interest for biotechnology investment in devices and other products to address the opioid crisis and addiction more generally. Historically, addiction is a market that has scared away pharmaceutical companies and investors, who viewed it as small and risky and one that would not lead to recovery of investment. However, NIDA’s medication development program expansion along with NIDA’s Office of Translational Initiatives and Program Innovations (OTIPI) are turning this around. OTIPI, which I highlighted previously on this blog, uses a wide array of funding mechanisms to support startups in developing or adapting devices, apps, and other technologies in ways that can better deliver treatment to people with substance use disorders and related conditions.
NIDA science continues to contribute knowledge to help guide policy. One example is from our annual Monitoring the Future (MTF) survey, which in 2019 showed steep increases in the use of vaping devices both for nicotine and for marijuana among teenagers. The survey also revealed that a large proportion of teens vaped because they liked the taste. When these vaping data (along with those of the National Youth Tobacco Survey) were released last November, it prompted the makers of the popular Juul devices to pull their mint flavored products from the shelves, and it prompted the FDA to finalize their enforcement policy on flavored vaping (e-cigarette) products.
The new scientific knowledge and innovations generated by our Institute in 2019 and the unprecedented investment in large-scale, coordinated studies through HEAL leave us poised to make considerable scientific progress in 2020 toward effective strategies for addiction prevention and treatment. As the ABCD study has already begun to, these new research programs will generate vast troves of data that promise new opportunities for collaboration and an accelerated pace of discovery.