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First fMRI Pilot Study Published on the Effects of Mindfulness-Oriented Recovery Enhancement on Reward Processing in Addiction

IMORE-fMRI-SB‘m pleased to announce that the first fMRI brain imaging study of Mindfulness-Oriented Recovery Enhancement (MORE) has been published in the open-access journal Evidence-Based Complementary and Alternative Medicine (Froeliger et al., 2017). My colleague Brett Froeliger and I conducted this proof-of-concept pilot study at his TRAIN Lab at the Medical University of South Carolina to examine the effects of MORE on reward processes in the brains of people addicted to cigarettes. A sample of 13 smokers participated in a study testing MORE versus a comparison group. All participants underwent two fMRI scans 8 weeks apart. Between the first and second fMRI scan, participants in the MORE group learned mindfulness and reappraisal skills to decrease addictive reactions to cigarettes and savoring skills to increase responsiveness to natural rewards (e.g., social connection, natural beauty, healthy behaviors). Participants in the comparison group completed research measures but did not receive any treatment. Relative to the comparison group, MORE was associated with significant decreases in smoking (66% decrease) and significant increases in positive emotions. Crucially, MORE participants evidenced significant decreases in neural activity while viewing cigarette images in reward-related brain regions including the ventral striatum and ventral prefrontal cortex. MORE participants also demonstrated significant increases in neural activity in these same reward-related brain regions while they savored positive, natural-reward related images. Importantly, increases in brain activity during savoring were significantly correlated with smoking reduction and increased positive affect. Though this study had a number of limitations, including the small sample size and lack of a randomized design, these pilot findings provide preliminary evidence that MORE may facilitate the restructuring of reward processes and play a role in treating the pathophysiology of nicotine addiction. These findings converge with results from our other psychophysiological studies indicating that MORE may restructure reward processes in prescription opioid misuse (Garland, Froeliger, & Howard, 2014; Garland, Froeliger, & Howard, 2015; Garland, Howard, Zubieta, & Froeliger, 2017). Taken together, these data provide initial support for my restructuring reward hypothesis which asserts that mindfulness training may enhance a domain-general cognitive resource for restructuring reward learning from valuation of drug-related rewards to valuation of natural rewards and thereby reverse the downward spiral of addiction.

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 Interview by Mind and Life Institute

mind_and-_lifeI was recently interviewed by Michael Juberg for the Mind and Life Institute, the world’s premier multi-disciplinary organization for the study of contemplative science. Michael and I had a wide ranging discussion that covered the span from philosophy to science to alleviating human suffering. He asked me some seriously thought-provoking questions that made me reflect back on the roots of my career and where it is all headed in the future. At the end of the interview, I offered a bit of advice for folks aspiring to become scientists in this field. The interview was really well done and I’m pleased to share it with you here.

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.

more-conceptual-framework-opioid

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 Research Funding: Targeting Chronic Pain among Veterans and Military Personnel with Mindfulness-Oriented Recovery Enhancement

 

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I was recently awarded $3.4 million in research funding from the Department of Defense Congressionally Directed Medical Research Program for a five-year clinical trial award entitled “Targeting Chronic Pain and Co-Occurring Disorders in the Community with Mindfulness-Oriented Recovery Enhancement.” To help me to carry out this pragmatic, large-scale randomized controlled trial, I will be supported by an interdisciplinary team of expert co-investigators from the University of Utah, including Jon-Kar Zubieta, Craig Bryan, Yoshio Nakamura, Gary Donaldson, and Bill Marchand.

The co-occurrence of chronic pain, psychological distress, and misuse of prescription opioids undermines the mission of the U.S. Military and inflicts suffering upon Veterans and their families. Approximately one-half of service members have chronic pain following deployment, and nearly one-fifth engage in opioid misusing behaviors like unauthorized dose escalation and use of opioids to self-medicate stress and anxiety. The state of Utah (where the proposed study will be conducted) has one of the highest incidences of nonmedical use of opioids in the U.S. and a rapidly increasing rate of prescription opioid-related deaths. Indeed, an estimated 21% of Utah adults were prescribed opioids during the past year, of which approximately one-in-five report taking more than prescribed. Given that military personnel and Veterans have higher rates of pain-related conditions than the general population, their risk for opioid-related problems is significantly enhanced.

military

New scientific findings indicate that because stress worsens pain and increases habit responses in the brain, individuals who cope with stress and pain through opioids are likely to have the most serious and difficult-to-treat opioid-related problems. The recent wars in Iraq and Afghanistan have been marked by repeated deployments involving serious combat-related and occupational stress. Unfortunately, there are no evidence-based treatments that simultaneously address pain, opioid misuse, and psychological distress. To fill this gap, this research proposal aims to conduct a pragmatic trial of a novel integrative medicine approach combining Mindfulness-Oriented Recovery Enhancement (MORE) with conventional opioid pain management for service members and Veterans. MORE aims to strengthen self-control over habit behaviors, increase flexible thinking under conditions of stress, and promote the sense of reward and meaning in the face of adversity.

This research project will help active duty service members and Veterans with chronic pain and stress who are at-risk for opioid misuse, and will also inform the treatment of civilians with similar issues. Should MORE prove to be effective in a community-based context, it could be easily transported into military installations and Veterans Administration Medical Centers in the U.S. and around the world, as well as in communities where no major military medical center is present. In these settings, MORE could be offered as a form of standard integrative health care provided to service members and Veterans.

A secondary objective of the proposed project is to utilize lab-based assessments and mobile technology to understand how MORE works to create therapeutic change, and to predict whether and when service members and Veterans are at risk for relapsing back to opioid misuse. To accomplish this objective, lab-based assessments will evaluate physiological reactivity to cues associated with past episodes of pain and opioid use, and a smartphone-based assessment will be used to evaluate opioid craving, pain, and negative mood in “the real world.” Because changes in heart rate and other physiological factors may indicate the extent to which a person’s brain has been triggered by opioid craving, this application of mind-body assessments to predict opioid misuse risk and treatment outcomes could facilitate early risk detection.

The final objective of the project is to understand for whom MORE works best, to help ensure more efficient healthcare resource allocation to the service members and Veterans who need it most.  The proposed project will enable health care providers to more effectively deliver low-cost treatment to prevent progression toward opioid addiction, thereby averting costly inpatient stays, discharge from active duty military service, and social, legal, and occupational problems among Veterans. Ultimately, the proposed research could significantly enhance the psychological and physical health of military personnel and Veterans by addressing the need for new integrative medicine treatment options with findings from the leading edge of science.

Research on MORE in the Annals of the New York Academy of Sciences – Targeting Hedonic Dysregulation with Mindfulness-Oriented Recovery Enhancement

mindfulness centered regulationIt is my pleasure to announce that the very first review paper summarizing the theoretical rationale and empirical evidence for Mindfulness-Oriented Recovery Enhancement (MORE) has been accepted for publication in the prestigious journal Annals of the New York Academy of Sciences. In this paper, I review data from multiple clinical studies on the biobehavioral mechanisms of MORE, and articulate a hedonic regulatory model of the intervention – proposing that restructuring reward processing is the final common pathway through which MORE ameliorates addiction, stress, and pain. I map this novel theoretical model onto an earlier conceptual framework of the neural circuitry underlying mindfulness-centered regulation of addiction (Garland, Froeliger, & Howard, 2014) and then describe new neuroimaging and psychophysiological data in support of the model. The paper abstract is as follows:

“Though valuation processes are fundamental to survival of the human species, hedonic dysregulation is at the root of an array of clinical disorders including addiction, stress, and chronic pain, as evidenced by the allostatic shift in the relative salience of natural reward to drug reward observed among persons with severe substance use disorders. To address this crucial clinical issue, novel interventions are needed to restore hedonic regulatory processes gone awry in persons exhibiting addictive behaviors. This article describes theoretical rationale and empirical evidence for the effects of one such new intervention, Mindfulness-Oriented Recovery Enhancement (MORE), on top-down and bottom-up mechanisms implicated in cognitive control and hedonic regulation. MORE is innovative and distinct from extant mindfulness-based interventions in that in unites traditional mindfulness meditation with reappraisal and savoring strategies designed to reverse the downward shift in salience of natural reward relative to drug reward, representing a crucial tipping point to disrupt the progression of addiction – something that no other behavioral intervention has been designed to do. Though additional studies are needed, clinical and biobehavioral data from several completed and ongoing trials suggest that MORE may exert salutary effects on addictive behaviors and the neurobiological processes that underpin them.”

The Mindfulness-to-Meaning Theory: A New Process Model of Mindful Emotion Regulation

I am feeling particularly thankful today to my colleagues Norman Farb (University of Toronto), Philippe Goldin (University of California – Davis), and Barbara Fredrickson (University of North Carolina – Chapel Hill), with whom I wrote and recently published the target article for the December issue of the esteemed, international journal Psychological Inquiry. Our target article, entitled “Mindfulness Broadens Awareness and Builds Eudaimonic Meaning: A Process Model of Mindful Positive Emotion Regulation,” articulates the Mindfulness-to-Meaning Theory, a new conceptual model of the cognitive, emotional, and neurobiological processes by which mindfulness might stimulate positive psychological states and lead to a sense of meaning in the face of adversity. In brief, the Mindfulness-to-Meaning Theory asserts that mindfulness allows one to decenter from stress appraisals into a metacognitive state of awareness that broadens attention to previously unnoticed pieces of information about one’s life, accommodating a reappraisal (i.e., a reframing) of adverse circumstances that reduces distress and promotes positive emotions. This reappraisal is then deepened and enriched when one savors what is pleasant, growth promoting, or meaningful in life, a process which motivates values-driven behavior and engenders a deeper sense of purpose and self-actualization.

The entire journal issue is devoted to the discussion of our new Mindfulness-to-Meaning Theory. Our work was the subject of 10 erudite commentaries from leading scholars in the fields of contemplative science, addiction neuroscience, clinical psychology, affective science, psycho-oncology, social psychology, and consciousness studies, who extended, challenged, and pushed our theory into new and wider applications. We responded to the commentaries with our own article “The Mindfulness-to-Meaning Theory: Extensions, Applications, and Challenges at the Attention–Appraisal–Emotion Interface,” which broadens the theory to address how mindfulness re-configures structures within working memory, describes mindfulness as a domain general resource for promoting emotion regulation flexibility, and suggests future directions to be pursued toward the establishment of a more comprehensive contemplative science.

The target article may be downloaded here and our response to the commentaries downloaded here.

May our work help advance the field to promote human flourishing!