New R01 Grant from the National Institute on Drug Abuse: Targeting Chronic Pain and Prescription Opioid Misuse in Primary Care with Mindfulness-Oriented Recovery Enhancement

nidaRecently, I was awarded a R01 grant from the National Institute on Drug Abuse to conduct a full-scale clinical trial of Mindfulness-Oriented Recovery Enhancement (MORE) as an intervention to reduce chronic pain and prescription opioid misuse in primary care. This five-year study will compare the efficacy of MORE to supportive therapy for 260 chronic pain patients receiving long-term opioid therapy who are at risk for opioid misuse.

Opioids may be medically necessary for some individuals experiencing prolonged and intractable pain, and most patients take medicine as prescribed. Unfortunately, opioids rarely completely alleviate chronic pain, and when taken in high doses or for long periods of time, can lead to serious side effects, including death by overdose, as well as risk for opioid misuse, which affects about 1 in 4 opioid-treated patients. Misusing opioids by taking higher doses than prescribed or by taking opioids to self-medicate negative emotions can alter the brain’s capacity for hedonic regulation, making it difficult to cope with pain (e.g., causing hyperalgesia – an increased sensitivity of the nervous system to pain) and experience pleasure in life (e.g., reducing sensitivity of the brain to natural reward). As such, non-opioid pain treatments that target hedonic dysregulation may be especially helpful for reducing chronic pain and prevent opioid misuse.

Multiple studies suggest that MORE improves hedonic regulation in the brain, resulting in decreased pain and an increased ability to savor natural, healthy pleasure. People who participate in MORE show heightened brain and body responses to healthy pleasures, and report feeling more positive emotions by using of mindfulness as a tool to enhance savoring. These therapeutic effects of MORE on savoring may be critically important, because findings from several studies show that increasing sensitivity to natural reward through savoring may lead to decreased craving for drugs – a completely novel finding for the field of addiction science (Garland, 2016). Our NIDA-funded R01 will provide a rigorous test of whether MORE improves chronic pain and opioid misuse by targeting hedonic dysregulation.

In our NIDA-funded R01, patients are receiving MORE at community medical clinics throughout Salt Lake City. Providing MORE in the naturalistic setting where most chronic pain patients seek medical care will make the therapy accessible to the people who need it the most. Ultimately, my hope is that this project will advance a new form of integrative healthcare, in which doctors and nurses work alongside social workers and other behavioral health professionals to help patients reclaim a meaningful life from pain.

New Research Funding: Neuroimaging Research on the Effects of Mindfulness-Oriented Recovery Enhancement on Hedonic Regulation

mindfulness-centered-regulation-in-brainChronic pain is often treated with extended use of opioid analgesics, yet these drugs can alter the brain in ways that may make it difficult to cope with pain and may reduce the experience pleasure in life. Mindfulness-based interventions appear to be a promising means of addressing these issues, but research is needed to understand how such interventions change the brain to reduce suffering.

To that end, in September, 2016, I was recently awarded a five-year phased innovation grant from the National Institutes of Health’s (NIH) National Center for Complementary and Integrative Health entitled Effects of Mindfulness-Oriented Intervention on Endogenous Opioid Mechanisms of Hedonic Regulation in Chronic Pain (R61AT009296). The objective of the project is to study the effects of an innovative mindfulness-based intervention on brain mechanisms linked with pain and pleasure.

In the first two-year phase of the study ($800,000), I (Principal Investigator), along with my Co-Principal Investigator Jon-Kar Zubieta (Co-Principal Investigator), chair of the University of Utah’s Department of Psychiatry, will use positron emission tomography (PET) neuroimaging to assess the effects of Mindfulness-Oriented Recovery Enhancement (MORE) on restoring brain levels of endorphins in patients with chronic back pain who are being treated with prescription opioids.

This study represents the first use of PET in the history of science to quantify the effects of a mindfulness-based therapy on levels of endogenous opioids in the brain.

We will also use functional magnetic resonance imaging (fMRI) methods to assess how mindfulness training through MORE may increase people’s capacity to savor natural pleasure from positive and meaningful events in everyday life – a capacity that becomes diminished over time through the deleterious effects of chronic pain and prolonged opioid use on the brain. We will use a fMRI paradigm developed by my Co-Investigator Brett Froeliger, Assistant Professor of Neuroscience at the Medical University of South Carolina.

This study aims to test whether MORE might reverse this insensitivity to natural reward by targeting the endogenous opioid system and brain reward functions.

Following a successful first phase of the project, a three-year second phase ($2.2 million) will investigate whether patients with a particular genetic makeup that affects the expression of opioid receptors in the brain might benefit more from the mindfulness-based treatment. The second phase of the project will also assess the dose of mindfulness skill practice as a predictor of changes in endogenous opioid function and clinical correlates.

Based on the results of previous research, we hypothesize that mindfulness meditation training through MORE will restore proper function to the brain’s opioid receptors.  We will be able to measure how MORE changes the brain’s ability to regulate pain and respond to natural rewards, as well as deepen our understanding of exactly how these changes in neural mechanisms happen.

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Overall, this project will unite expertise in mindfulness-based interventions with expertise in neurogenetics and the use of PET and fMRI to probe the neurobiological mechanisms of pain and emotional experience. By elucidating a key mechanism of meditation-based therapies, this program of translational research will further the emerging field of social work neuroscience and enable us to rapidly optimize MORE to increase the effectiveness of the intervention as it is rolled out in clinical practice.

 

 

New Paper Accepted for Publication – Opioid Attentional Bias and Cue-Elicited Craving Predict Future Risk of Prescription Opioid Misuse

opioid_probe Today I had a new paper accepted for publication in the prestigious addictions journal, Drug and Alcohol Dependence. This paper, coauthored with my colleague Matthew Howard, describes new findings from a randomized controlled trial of Mindfulness-Oriented Recovery Enhancement for chronic pain patients prescribed long-term opioid painkillers. The new findings demonstrate that the extent to which an individual finds his or her attention automatically captured by opioid-related images (e.g., the image of an opioid pill bottle) significantly predicts whether they will misuse opioids 20 WEEKS LATER after completing treatment.

Before patients participated in the research treatments, they completed a dot probe task in which they were shown two pictures (displayed either for 200 ms, or 2000 ms), side by side, on a computer screen, and were asked to “choose the side with the dot” by clicking a button on a keypad. The computer recorded their reaction times down to the millisecond. We found that compared to people who did not misuse opioids at follow-up, people who ended up misusing opioids 3 months after completing treatment were significantly faster to choose the side with the dot when the dot replaced an opioid photo than when it replaced a neutral photo.  This reaction time difference indicated that their attention was captivated by opioids. This effect was evident for cues presented for 200 ms (that’s one-fifth of a second!), suggesting that this attentional bias occurred automatically, unconsciously, and before participants even had time to think about what they were doing. Even after statistically controlling for pain levels, opioid dependence, and pre-treatment opioid misuse, people with a stronger opioid attentional bias prior to entering treatment were significantly more likely to misuse opioids 20 weeks later than people with less attentional bias to opioids.

So what is the significance of this research study for helping people with addiction and chronic pain? The study findings suggest that people who take opioids for chronic pain may develop an automatic tendency to be fixated on their medication, even when they don’t want to be. This tendency might make it difficult to stop thinking about opioids, causing craving, distraction, or other kinds of disruption in life. It might even result in or foretell opioid misuse down the line, long after a person has completed treatment. Using a performance-based dot probe test delivered by computer to detect risk for future opioid misuse may help physicians and health care providers make more informed decisions about whether and when to prescribe opioids to patients suffering from chronic pain.

New Paper Accepted for Publication! The Downward Spiral of Chronic Pain, Prescription Opioid Misuse, and Addiction: Cognitive, Affective, and Neuropsychopharmacologic Pathways

My colleagues and I recently had a new paper accepted for publication in the highly esteemed, international journal Neuroscience and Biobehavioral Reviews. This paper draws upon current neuropsychopharmacologic research to provide a conceptual framework of the downward spiral leading to opioid misuse and addiction among chronic pain patients taking prescription opioids for pain relief. In brief, we theorize that addictive use of opioids is the outcome of a cycle initiated by chronic pain and negative emotions, leading to attentional hypervigilance for pain and drug cues, dysfunctional connectivity between self-referential and cognitive control networks in the brain, and allostatic dysregulation of stress and reward circuitry. We conclude the paper by introducing Mindfulness-Oriented Recovery Enhancement (MORE) as a potentially effective approach to disrupting the downward spiral. This is a particularly exciting publication for our research team, because it lays the theoretical groundwork for developing new and innovative efforts to help people recover from chronic pain and opioid addiction.

New Paper Accepted for Publication: Mindfulness-Oriented Recovery Enhancement Reduces Pain Attentional Bias in Chronic Pain Patients

My colleague Matthew Howard and I recently had a paper accepted for publication in the internationally-recognized journal, Psychotherapy and Psychosomatics. This paper describes a subset of findings from a randomized controlled trial (RCT) of Mindfulness-Oriented Recovery Enhancement for chronic pain patients who have been prescribed long-term opioid treatment (e.g., oxycontin, vicodin) for pain management. The study is the first in the scientific literature to demonstrate that a mindfulness-oriented intervention can reduce the pain attentional bias. In this study, 67 individuals suffering from low back pain, neck pain, arthritis, fibromyalgia, and other pain conditions were randomly assigned to participate in MORE or a support group and began treatment.

Participants in the MORE group received instruction in applying mindfulness and other psychological techniques to: discriminate between nociception (i.e., the signal that the body is being damaged), pain, and suffering; become aware of their automatic pain coping habits; disrupt the link between negative emotions, fear of pain, and catastrophizing; refocus attention from pain and stress to savor pleasant experiences; manage pain and opioid dependence; reduce stress; promote acceptance versus suppression of difficult experiences; and develop a mindful recovery plan. Mindfulness training involved meditation on breathing and body sensations, with an emphasis on metacognitive awareness and shifting from affective to sensory processing of pain sensations. In other words, participants learned to step back and observe their pain as innocuous sensory information rather than as an emotionally-anguishing event – e.g., seeing their pain as “sensations of heat, tightness, tingling, or coolness” rather than “terrible agony.”

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Participants in the support group were led to disclose their feelings and thoughts about topics related to chronic pain and opioid-related problems, as well as to provide advice and emotional support for their peers. The format of the support group was similar to conventional support groups used in many medical and psychotherapy settings.

We hypothesized that MORE would help participants to fixate less on their pain – freeing them to refocus on the meaningful, beautiful, or rewarding aspects of their lives. To measure attentional fixation on pain, or pain attentional bias, we used a dot probe task. In this task, participants were presented with two images, side by side, on a computer screen. One of the images was a pain-related image – the other was a neutral image. The images were presented for either 2 seconds or 200 milliseconds, and then were replaced with a dot. Participants were asked to press a button to indicate location of the the dot. Previous research demonstrates that chronic pain patients are faster to respond to pain images than neutral images, indicating that they exhibit an attentional bias, or attentional fixation, on pain-related information. Hence, people in chronic pain tend to automatically focus their attention on pain and things related to pain. This attentional fixation might occur unconsciously, without a person intending to focus on pain or even realizing that it is happening.

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In summary of our study results, we found that MORE led to significant reductions in the pain attentional bias, whereas the support group did not have any effect on pain attentional bias. Importantly, participants in MORE who experienced the largest decreases in the pain attentional bias felt like they had greater control over their pain following treatment. In addition, those people who felt that MORE had helped them to become less reactive to negative thoughts and feelings also had less pain attentional bias following treatment.

MORE_reduces_pain_AB

In conclusion, MORE appears to help people suffering from chronic pain and opioid-related problems learn to free their minds from fixating on pain, and in so doing, empower them to regain control of their lives.

Leading-Edge Science Supports the Notion of Recovery

Image By Sandy Burns

Over the past several decades there has been an explosion of research demonstrating that our feelings and thoughts are closely tied to the function of our brains, so much so that the 1990s were heralded as the “Decade of the Brain” by the Library of Congress and the National Institutes of Health. Neuroscience has come to have a powerful influence on our concepts of mental health, leading many people to believe that forms of psychological suffering like depression, anxiety, and addiction are caused by “biochemical brain imbalances.” While this view has removed a great deal of the stigma that was once associated with chronic mental health problems, it also may send the implicit and unfortunate message that change and recovery is not possible. If depression, anxiety, and addiction are diseases of the brain, how can anyone possibly change their brain? Isn’t the function and structure of the brain, like any other organ, determined by genes and fixed from birth?

The answer emerging from neuroscience research of the past decade is an unequivocal “NO!” We now know that the brain grows and changes throughout childhood, adolescence, and even into adulthood and old age! A number of factors can stimulate changes in the brain, known as neuroplasticity, including stress, diet, exercise, and even learning experiences. So, if chronic states of depression, anxiety, and addiction are partially the result of brain dysfunction (and, to be clear, a number of scholars have raised serious and important challenges to the neurobiological model of mental illness), many scientific studies demonstrate that learning and practicing new ways of thinking, acting, and responding to the challenges in our lives can change the way our brains function! Research is beginning to demonstrate that the very structure of our brains can be modified by mental training, not unlike the way people lift weights to build the size and strength of their muscles through physical training.

So what does all this groundbreaking and fascinating science mean for the idea of recovery from mental health and substance abuse problems? It explains how addiction treatment and mental health services can help people who have been diagnosed with a mental and/or substance use disorder to transcend their challenges to live a healthy and meaningful life. Innovative ways of helping people recover are continually being developed and tested, with promising results. The Trinity Institute for the Addictions at the FSU College of Social Work is dedicated to advancing new methods of promoting recovery.  Through my work at Trinity and through my prior work at the University of North Carolina at Chapel Hill, I have developed a new type of mental training program for people struggling with addiction, mental health problems, and chronic pain called Mindfulness-Oriented Recovery Enhancement, or MORE. MORE combines mindfulness training, cognitive-behavior therapy, and positive psychological principles into an integrative treatment strategy designed to help people increase self-control over their unhealthy habits and/or addictive behaviors, reduce their negative emotions (like feelings of anxiety, anger, and hopelessness), and improve their psychological well-being. I am currently conducting a clinical trial to test MORE as a way to combat chronic pain and problems related to prescription painkiller use – a growing epidemic in the U.S. and a frequent headliner in Florida’s news media.

Although this study is still in process, other studies suggest that mental training programs can be very helpful. For example, in previous research my colleagues and I found that mindfulness training reduced chronic pain symptoms by 38 percent and psychological stress by 31 percent! Another one of our studies indicated that mindfulness training helped people struggling with alcoholism to recover after being exposed to addictive triggers by calming their nervous system reactivity back towards baseline levels.  Other research suggests that mental training programs including cognitive-behavior therapy and mindfulness training can alter brain function and significantly reduce the symptoms of depression and anxiety, often with lasting positive effects.

The Substance Abuse and Mental Health Services Administration defines recovery as “a process of change through which individuals improve their health and wellness, live a self-directed life, and strive to reach their full potential” (SAMHSA, 2011). The latest neuroscience findings on neuroplasticity and results from clinical research on psychological therapies like mindfulness training and cognitive-behavior therapy provide strong evidence for the notion that recovery from mental health problems and substance abuse is possible. Time and time again, cutting-edge science and clinical findings reveal a simple, hopeful, and powerful truth: treatment is effective, and people do recover.

New Research Study Accepted for Publication! “Attentional bias for prescription opioid cues among opioid-dependent chronic pain patients”

I am excited to announce that a scientific article I wrote with my colleagues Brett Froeliger (Duke University), Steven Passik (Vanderbilt University), and Matthew Howard (University of North Carolina at Chapel Hill) was recently accepted for publication in the Journal of Behavioral Medicine. This article details the first evidence of an attentional bias toward prescription opioid cues ever documented in the scientific literature! We found that among a sample of people with chronic pain who were prescribed opioid painkillers, those individuals who met diagnostic criteria for opioid dependence paid significantly more attention to opioid-related images than opioid-users in chronic pain who were not dependent on opioids. To measure attention to opioids, we used a neurocognitive task that looked something like this:

Participants were shown two pictures (displayed either for 200 ms, or 2000 ms), side by side, on a computer screen, and were asked to “choose the side with the dot” by clicking a button on a keypad. The computer recorded their reaction times down to the millisecond. We found that, compared to non-dependent opioid users, opioid dependent people were significantly faster to choose the side with the dot when the dot replaced an opioid photo than when it replaced a neutral photo.  This reaction time difference indicated that their attention was captivated by opioids. Also, the more they reported craving their opioid medication, the more their attention was biased towards the opioid photos. This effect was evident for cues presented for 200 ms (that’s one-fifth of a second!), suggesting that this attentional bias occurred automatically, unconsciously, and before participants even had time to think about what they were doing.

So what does this research mean in terms of helping people with addiction and chronic pain? The study findings suggest that people who take opioids for chronic pain may develop an automatic tendency to be fixated on their medication, even when they don’t want to be. This tendency might make it difficult to stop thinking about opioids, causing craving, distraction, or other kinds of disruption in life. It might even lead to taking more medication than is necessary, although the current research study cannot answer that question.

If future studies replicate these findings, the opioid attentional bias may be an important treatment target for people struggling with prescription opioid misuse and addiction. Mindfulness-Oriented Recovery Enhancement (MORE) is designed to address attentional bias and may be particularly helpful in that regard. My preliminary research on MORE as a treatment for alcoholism found that MORE had a significant effect on attentional bias for alcohol cues. Research is currently underway to determine if MORE can have a similar effect on the opioid attentional bias.