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Oklahoma State University

Addressing Addiction

Friday, November 1, 2019

Osteopath manipulative treatment (OMT) is being evaluated by researchers at OSU Medicine for its use in helping treat pain without opioids.

OSU Medicine's National Center for Wellness & Recovery takes a broad approach to solving the opioid crisis

The nationwide opioid crisis has definitely made it to Oklahoma — and the National Center for Wellness & Recovery at OSU Medicine is leading the battle against it.

A look at the numbers:

  • In 2017, Oklahoma was one of the top opioid- prescribing states, with 88.1 prescriptions written per 100 people.
  • More than 3,000 Oklahomans died from drug overdoses from 2015-2018.
  • Oklahoma leads the nation in nonmedical use of prescription pain medicine among people aged 12 or older, based on a 2017 study completed by the federal Substance Abuse and Mental Health Services Administration.

Addiction to prescription opioid medications is widespread — crossing race, education, age, gender, levels of education and economic classes. Too often, promising lives are caught in the grip of addiction.

Doctors now know that addiction is not a lifestyle choice but a chronic brain disease, caused by a confluence of genetic, biological, behavioral and social factors. When once we thought detox and in-patient medical care were required, now we have pharmacological treatments to take the place of detox for opioids and strong outpatient medical systems with recovery support and management that allow health care systems to offer excellent care for more of the population.

Although we have made great strides in understanding the science of addiction, more research is needed to improve treatment results and to prevent addiction altogether.

In November 2017, OSU Medicine President Kayse Shrum, D.O., established the National Center for Wellness & Recovery at OSU Medicine to address the opioid epidemic. Its mission is to improve lives affected by pain and substance use disorders through clinical services, training, research and advocacy. The center aims to promote collaborative and interdisciplinary approaches to prevention, care, education, research and public policy associated with the study, treatment and public understanding of pain and substance use and misuse.

Randall Davis

Dr. Randall Davis, a professor of pharmacology, is part of a team at OSU Medicine working to improve substance abuse treatment outcomes.

“Without evidence to support our practices, we could not train providers to treat addiction,” said Julie Croff, Ph.D., executive director of the center. “Research is necessary to inform our clinical services, training and advocacy initiatives.”

In order to address addiction, the center employs several overlapping, intersectional models of research. First, it’s engaged in translational research, which involves the use of cellular and animal models to inform human subjects research. Second, the center is engaged in innovative research across the life course, including multi- generational approaches. Third, it engages in research across the ecological levels of influence from individual level to community.

The translational research involves multidisciplinary teams.

“Addiction is a brain disease that has multiple intersecting causes, so it is ideal that we work across fields to develop a comprehensive approach to treatment and prevention of addiction,” said Alicia Ford, Ph.D., clinical assistant professor of psychiatry and behavioral sciences. By creating partnerships between clinical and biomedical scientists, OSU seeks to reduce lag time between important findings and clinical outcomes. For example, opioids and other substances of abuse cause changes in many areas and pathways of the brain and often lead to decreases in a person’s cognitive functioning, such as lower attention spans and impulse control. When a person stops using substances, it is expected that they will experience some level of cognitive improvement over time. Dr. Ford is collaborating with Dolores Vazquez Sanroman, Ph.D., assistant professor of anatomy and cell biology, on a series of studies that evaluate the level of natural brain recovery that occurs during early abstinence. Repeated cognitive assessments and blood samples from patients are taken to evaluate changes in cognitive performance and supporting biomarkers over time.

“Our initial results indicate that when people enter inpatient treatment for opioid abuse, they are performing at one-half to one standard deviation below expectation in multiple cognitive areas,” Ford said. “After one month of abstinence they demonstrate improvements in cognitive performance, though not yet a full recovery.”

Dr. Vazquez Sanroman is analyzing multiple blood samples from each patient to determine if there is a pattern of biological changes that relate to this cognitive recovery. “In particular, we are looking at the levels of brain-derived neurotrophic factor. BDNF is a neural protein that plays an important role in neurogenesis and neural plasticity — the brain’s ability to form new neurons and to change in response to the environment,” she said. Our translational teams are more effective by applying techniques from within their academic discipline to projects in partnership with multidisciplinary teams.

The center also values understanding the life course of addiction. In her lab, Vazquez Sanroman is investigating rodent models for BDNF as a potential biological marker underlying the mechanism of action of opioids on the adolescent central nervous system.

“Using a rodent model of place preference, animals that preferred to expend time on the opioid-associated environment showed a dysregulation on BDNF levels in brain areas involved in addiction,” Vazquez-Sanroman said.

As part of the life course model, the center seeks to understand the biological and behavioral impacts on addiction.

Croff has a research trajectory examining the role of mother’s substance use directly and indirectly acting upon birth and child outcomes. Croff and Amanda Sheffield Morris, Ph.D., hope
to win a grant from the National Institutes of Health as part of a multisite consortium. The goal of the HEALthy Brain and Cognitive Development (HBCD) study is to develop a research protocol that will gather data on potentially important factors about the environment of mother and 
baby, including drug and alcohol use, environmental toxins, social interactions and nutrition. The final protocol will be established to follow the development of babies until age 10. According to the National Institute on Drug Abuse, “Medicine has thus far lacked detailed baseline standards of normative brain development in childhood, and HBCD will help produce such standards. The information gained from the study will create an invaluable reference for pediatricians, pediatric neurologists, and psychiatrists.”

Another area of focus for the center’s research is alternative options for chronic pain. Many people with opioid addiction were first exposed to the drug via prescription to treat chronic pain. Because opioid medications are powerful analgesics, it can be difficult for patients with continued pain to stop their use without experiencing potent withdrawal symptoms. Over time, opioid use can escalate, and many individuals will develop an opioid addiction. Persons with opioid addiction and chronic pain are at a higher risk for relapse unless their pain can be managed with other methods.

“Using a rodent model of place preference, animals that preferred to expend time on the opioid-associated environment showed a dysregulation on BDNF levels in brain areas involved in addiction,” Vazquez-Sanroman said.

As part of the life course model, the center seeks to understand the biological and behavioral impacts on addiction.

Croff has a research trajectory examining the role of mother’s substance use directly and indirectly acting upon birth and child outcomes. Croff and Amanda Sheffield Morris, Ph.D., hope
to win a grant from the National Institutes of Health as part of a multisite consortium. The goal of the HEALthy Brain and Cognitive Development (HBCD) study is to develop a research protocol that will gather data on potentially important factors about the environment of mother and 
baby, including drug and alcohol use, environmental toxins, social interactions and nutrition. The final protocol will be established to follow the development of babies until age 10. According to the National Institute on Drug Abuse, “Medicine has thus far lacked detailed baseline standards of normative brain development in childhood, and HBCD will help produce such standards. The information gained from the study will create an invaluable reference for pediatricians, pediatric neurologists, and psychiatrists.”

Another area of focus for the center’s research is alternative options for chronic pain. Many people with opioid addiction were first exposed to the drug via prescription to treat chronic pain. Because opioid medications are powerful analgesics, it can be difficult for patients with continued pain to stop their use without experiencing potent withdrawal symptoms. Over time, opioid use can escalate, and many individuals will develop an opioid addiction. Persons with opioid addiction and chronic pain are at a higher risk for relapse unless their pain can be managed with other methods.

Osteopathic manipulative treatment, or OMT, is a set of techniques that osteopathic physicians use to treat musculo- skeletal problems. The techniques include various hands-on stretching, gentle pressure and resistance procedures. OMT has been found to be an effective treatment for low back pain, the most common type of non-cancer pain.

Ford and Vazquez Sanroman (co-principal investigators) are leading a two-year research study funded by the American Osteopathic Association to evaluate the use of OMT with patients who have both opioid addiction and chronic back pain. Their interdisciplinary team, with colleagues Randall Davis, Ph.D., professor of pharmacology; Robin Dyer, D.O., chair of osteopathic manipulative medicine; and Croff will be evaluating the effectiveness and potential mechanisms of OMT in reducing pain and improving substance abuse treatment outcomes.

“Both opioid addiction and chronic pain have known effects on one’s mood, cognition, and general life functioning,” Ford said. “These are accompanied by a host of neurobiological changes. We hope that by providing an effective non- medication treatment for pain that our participants will experience improvement in multiple areas and be more successful in remaining abstinent from opioids.”

Center researchers are also exploring ecological models of addiction. Research on individuals can determine how training medical professionals can transform treatment of their patients and how patients recover with different treatments. Research at the interpersonal level can answer questions about how to support families of individuals living in active addiction and the role that group therapeutic services play in recovery. Research at the health system level can inform how we can best screen for and identify this disease. And research at the community level can help us prevent substance use disorders by targeting the underlying causes of pain and addiction. Our translational teams will continue to seek answers across the lifespan for individuals, families, schools, churches, health systems and communities.

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