Halting opioid abuse aim of several grants from NIH, CDC

Tapped for their work aimed at stemming opioid abuse and halting what has become an epidemic in the United States, researchers at Washington University School of Medicine in St. Louis have received federal grants totaling more than $10 million from the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC). The grants are part of a nationwide push to fund research targeting the epidemic.

At the School of Medicine, much of the grant funding is directed toward improving treatments for chronic pain; curbing rates of opioid-use disorder and overdoses; gaining a better understanding of why, and among whom, overdoses and deaths are occurring; helping patients achieve long-term recovery from opioid addiction; and other efforts.

Among those receiving grants is Robert W. Gereau IV, PhD, the Dr. Seymour and Rose T. Brown Professor of Anesthesiology at Washington University, who is collaborating with John A. Rogers, PhD, a professor of biomedical and neurological engineering at Northwestern. They have a two-year, $4.2 million grant from NIH — as part of its HEAL (Helping to End Addiction Long-Term) Initiative — to develop an implantable device that would automatically deliver life-saving doses of the drug naloxone (Narcan) to people experiencing acute opioid overdoses. The device they are developing would deliver naloxone to a person experiencing respiratory distress, the primary cause of overdose deaths.

They envision the devices being implanted under the skin in people who have been treated for opioid-use disorder or who have been incarcerated after abusing opioids, resulting in long periods of abstinence from opioids.

“People in treatment for opioid addiction and those who have been incarcerated have a high risk of relapse,” said Gereau, who directs the Washington University Pain Center. “While Narcan can prevent deaths, it is not always readily available, and even if it is available, there is not always another person around to administer the medicine. This device could fill that void, helping to ensure that if a person relapses and gets into trouble, there would be a fail-safe way to deliver the drug that could save them.”

A second grant, also from the NIH HEAL Initiative, is providing more than $1.5 million to Gereau and colleagues at Vanderbilt University. The group is investigating ways to block a nerve cell receptor that Gereau’s laboratory has studied for many years. The receptor, called mGlu5, is known to interfere with the pain response, and drugs that interfere with that receptor potentially could provide sustained pain relief without causing the euphoria that makes opioid drugs so seductive.

Previously developed compounds aimed at interfering with the mGlu5 receptor haven’t made it through clinical trials. But in the new study, Gereau and his colleagues will test new, highly selective modulators of that receptor with the hope that they can identify effective pain-killing compounds with much lower potential for abuse and misuse.

Impact on young brains

Another grant focuses on the impact of opioids on expectant mothers and their babies. Cynthia E. Rogers, MD, an associate professor of psychiatry and of pediatrics, and Christopher D. Smyser, MD, an associate professor of pediatric neurology, share the renewable, one-year $1 million planning grant with colleagues from Northwestern.

Using advanced neuroimaging and clinical measurements, the team will test the feasibility of assessing healthy brain development in infants compared to brain development in the babies of mothers who used opioids during pregnancy. The project involved in this grant will assess brain development only in babies who have been exposed to opioids.

The grant also will involve analysis of legal and ethical issues surrounding opioid use by pregnant women in the states of Missouri and Illinois, where the legal approaches regarding drug use by expectant mothers are very different.

“Washington University neuroscientists and experts on substance use, child welfare, and maternal and child mental health will collaborate with experts in neuroscience, bioethics, pediatric population health, addiction and other specialties at Northwestern,” Rogers said. “Together, we hope to get a better handle on the impact of the opioid epidemic and the risk it poses to the health and development of children and families.”

Simultaneous treatments

Another grant will fund research involving people who inject illicit drugs. Drug users also accidentally may inject bacteria, viruses or fungi into their bloodstreams, putting them at high risk for life-threatening infections of heart, bone, liver or other organs. Successfully treating such infections requires simultaneously treating such infections and the underlying substance-use disorder. Otherwise, patients are likely to return to a hospital later with the same infection, sometimes in worse form.

To tackle both issues, the CDC has awarded $1.57 million to a multidisciplinary team at the School of Medicine, the Barnes-Jewish Consortium and the University of Missouri-St. Louis.

Michael J. Durkin, MD, an assistant professor of medicine in the Division of Infectious Diseases at Washington University, will lead the urban arm of the project, based at Barnes-Jewish Hospital. Meanwhile, Stephen Yuan-Tung Liang, MD, an assistant professor of medicine in the school’s infectious diseases and emergency medicine divisions, will lead the rural arm of the study at Missouri Baptist Sullivan Hospital in Sullivan, Mo., and Parkland Health Center in Farmington, Mo. Both hospitals serve residents in rural Missouri.

The researchers will work to develop and implement treatment plans that include prescription drugs for withdrawal and maintaining sobriety, naloxone rescue kits in case of overdose, vaccinations and HIV-prevention medications, education on safe injection practices, and referral to harm-reduction programs and other appropriate services.

“The goal is to provide a full suite of services and to develop an implementation toolkit to guide other hospitals struggling with the opioid epidemic,” Durkin said. “We hope to provide treatment for at least 400 people at our three sites during the course of the next year and a half.”

While not all NIH and CDC grants have been announced, other related grants to Washington University investigators include:

• A three-year, $447,000 grant for Sarah Hartz, MD, PhD, an assistant professor of psychiatry, to work with educational leaders to implement a medical school curriculum to ensure that graduating medical students have the training necessary to be certified in medication-assisted treatments for opioid-use disorder. The funding also would address such training for residents in psychiatry, emergency medicine and internal medicine. Other investigators involved in the training and curriculum development include Carrie Mintz, MD, an instructor in psychiatry, David Liss, MD, an assistant professor of medicine in the Division of Emergency Medicine, and Evan S. Schwarz, MD, an associate professor of emergency medicine. This grant is from the Substance Abuse and Mental Health Services Administration of the U.S. Department of Health and Human Services.
• Yu-Qing Cao​, PhD, an associate professor of anesthesiology at the Washington University Pain Center, has received a two-year, $500,000 grant from the National Institute of Neurological Disorders and Stroke of the NIH to validate the potassium channel TRESK as a novel target for chronic pain medicine. The Cao lab is particularly interested in migraine headaches and developing ways to prevent pain from such headaches without use of opioid drugs.
• Ann Marie Dale,​ PhD, an associate professor of medicine, has received a three-year, $707,918 grant from the NIH to develop and test evidence-based workplace guidelines to reduce opioid use and misuse among working-age people. Her research primarily will focus on the construction industry. Workers in this industry are among the populations most affected by the opioid crisis.

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