everyone. Welcome to this presentation from the PCSS on mindfulness oriented recovery enhancement. And I want to introduce our speaker, Dr. Eric Garland. He is a Dr. Eric Garland is a PhD. He's a distinguished endowed chair in research, distinguished professor, and associate dean for research in the University of Utah College of Social Work. And he is also director of the Center on mindfulness and integrative health intervention development. Dr. Garland is the developer of an innovative mindfulness based theory therapy founded on insights derived from effective neural science called mindfulness oriented recovery enhancement or more. He has published more than 220 scientific manuscripts and received more than 70 million in research grants to conduct clinical trials of mindfulness for addiction and chronic pain. In recognition of his expertise, Dr. Garland was appointed by the NIH director, Dr. Francis Collins to the NIH HEAL multidisciplinary working group to help guide the 1.1 billion HEAL initiative to use science to halt the opioid crisis. In a recent bibliometric analysis of mindfulness research published over the last 55 years, Dr. Garland was found to be the most prolific author of mindfulness research in the world. Now, I just want to say one more thing before I let Dr. Garland takes over is that you will receive a survey via email probably tomorrow to complete. And once you complete the survey, a certificate will be sent to you. So anyway, it is my privilege to introduce Dr. Eric Garland. Thank you so much, Kathy. And it's a pleasure to be with all of you today. I'm really looking forward to telling you about my work. So just to begin, it's just disclosure, I am a licensor to Behavior, LLC. But I won't be speaking about that work today. And the target, the overarching goal of PCSS is to train healthcare professionals and evidence based practices for the prevention and treatment of opioid use disorders, particularly in prescribing medications, but also, as well for the prevention and treatment of substance use disorders. So to begin in 2015, Nobel Prize winning economists case and beaten found that for the first time in many decades, the US mortality rate was rising precipitously, which they attributed in large part to the opioid crisis, a crisis that has been termed a disease of despair in the sociological and epidemiological literature. And the disease of despair, as many sources from the rising tide of income inequality, to the lack of opportunity, to intergenerational violence and trauma, and the egocentric materialism and social isolation, that is such a part of modern culture. And in the face of this vacuum of meaning, it was perhaps inevitable that life would become more painful. And indeed, it did rates of chronic pain sort in the US where an estimated 50 million Americans experience pain each year. And to meet this epidemic of pain opioid prescriptions climb. In 2015 38% of the US population was prescribed an opioid that year. And this dramatic increase in opioid prescriptions was paralleled by a rising incidence of opioid misuse and opioid use disorder. In 2020 9.3 million Americans misuse prescription opioids, and 2.7 million had an opioid use disorder. Of the 9.3 million who misused opioids, 43.6% obtained the opioids from a healthcare provider. And that tells me that chronic pain is continuing to fuel the opioid crisis to this day. I want to begin with a clinical anecdote, kind of put things together. So a patient came to see me for help with chronic pain and opioid related problems. He had received a series of five failed back surgeries, and after each one had been prescribed escalating doses of opioids. He knew he had a problem with opioids, he knew he was taking too high of a dose. But as he so poignantly stated to me, I just don't want to be in pain. I asked him to tell me about a time when he wasn't in so much pain, or maybe when his pain didn't bother him at all. He told me that on the weekends when his grandkids came over, and he watched them play in the backyard, he became so focused and so absorbed in watching them play that it brought joy to his heart. And in that moment, he didn't really notice his pain, his pain was temporarily gone. And so was his desire for opioids. And this clinical anecdote, which is probably familiar to those of you who work with patients like this, hints at an untapped therapeutic mechanism that could be potentially leveraged to help heal the opioid epidemic. To understand this claim, we need to understand the role that hedonic dysregulation plays in pain, pleasure and addiction. Traditionally in Western philosophy, pleasure and pain are considered opposites on a hedonic balance, such that increasing experiences of pain are thought to outweigh the experience of pleasure in everyday life. Modern neurobiology suggests that pleasure and pain are not mere opposites, but actually operate through a common emotional currency in the brain, mediated by the mesocortico-limbic dopamine circuit and the endogenous opioid system. And these same hedonic brain circuits become hijacked by addictive drugs like opioids through an allostatic process, in which chronic exposure to opioids results in neuroplastic changes in the brain that increase sensitivity to pain, stress and drug related cues, while decreasing sensitivity to the pleasure and meaning derived from naturally rewarding objects and events in the social environment. So in other words, as the individual becomes more and more dependent on opioids just to feel okay, they become less able to extract a sense of healthy pleasure, joy and meaning out of everyday life. And this drives them to take higher and higher doses of the drug to preserve a dwindling sense of well being. And this leads to a downward spiral of loss of self control over opioid use that results in opioid dose escalation and opioid use disorder. But we know that not all patients misuse opioids or become addicted to them. In fact, most don't. So it's an interesting question. Why can some patients take opioids as prescribed by their physician, whereas others go on to misuse them or become addicted to them? And answering this question has really been the focus of much of my basic science research program. So to answer this question, we use tasks from cognitive neuroscience, including the dot probe task. In the dot probe task, there's a computer screen and it's split in two. On one side of the screen is a pain related image. On the other side of the screen is a neutral image. These images are displayed for a very brief amount of time, about a fifth of a second, so flash, and they disappear and a dot pops up. The participant's task is to choose the side with the dot and the computer measures reaction times. It turns out there's a large body of research to show that people with chronic pain are faster to find the dot when it replaces a pain image than when it replaces a neutral image, indicating that people with chronic pain have an attentional bias or a hyper fixation of attention on pain related information. We also pair neutral images and naturally rewarding positive images. And we pair opioid images and neutral images. And several years ago, my research group was the first to find that people with chronic pain who had an opioid use disorder are faster to find the dot when it replaces an opioid image than when it replaces a neutral image, indicating that they have this attentional bias towards opioids, this hyper fixation of attention towards opioids. And this opioid attentional bias has important clinical consequences. It significantly predicts opioid misuse 20 weeks following the end of treatment. So these data suggests that opioid misuse is associated with increased sensitivity to opioid related cues and an opioid attentional bias. But in my research center we also measure hedonic dysregulation with another task from neuroscience called the emotion regulation task. In this task, participants are presented with emotional images. In response to negative emotional images, they're asked to either view the image or reappraise the image by reframing the meaning of the content of the image in such a way as to reduce its negative emotional impact. So to reappraise this image of this mother and child screaming in fear, one might think the mother and child faced the tragedy, but in facing the tragedy, it brought them closer together as a family. And thinking about it this way might reduce the negative emotions. In response to positive emotional images like this father and son at the beach, participants are asked to either view the image or to savor the image by mindfully focusing their attention on what is pleasant, beautiful and good in the image, and appreciating and amplifying any positive emotions and pleasant body sensations arising during the savoring practice. And during this task, we measure an array of psychophysiological variables, including heart rate variability, which is the beat-to-beat variation in heart rate that is driven by the parasympathetic nervous system and governed by a higher order network of brain structures involved in regulating attention and emotion. Several years ago, my colleagues and I found that relative to patients who take opioids as prescribed, here depicted in these blue bars, opioid misusing chronic pain patients, here depicted in the red bars, showed significant blunting of heart rate variability during reappraisal, viewing positive images, and savoring positive images, indicating that they have a selective deficit in the ability to shift their emotions in a positive direction. And we find converging evidence for this in EEG data. So here in the top center panel, you can see brain waves from patients who don't misuse opioids. These individuals are able to decrease their brain's reactivity to negative emotional images. When they reappraise those images, they're able to calm down their brain's reactivity to the negative emotions. Beneath, you can see brainwaves from patients who misuse opioids. These individuals, not only can they not reappraise effectively, but when they reappraise, it actually backfires, and it aggravates their brain's reactivity to the negative emotional stimulus. And all the way on the right, you can see brainwaves during positive emotion regulation. In blue, you can see here that people who don't have an opioid use disorder, they're able to increase their brain's response from viewing positive images to savoring positive images. Beneath in red, you can see brainwaves from patients with an opioid use disorder. Here you see just total blunting of brain response during positive emotion regulation. These folks just can't make themselves feel better naturally. And these deficits in negative emotion regulation and positive emotion regulation are associated with higher levels of opioid craving and actually predict opioid misuse in the future. So if this is the problem, if opioid misuse and addiction is associated with this blunted capacity to increase healthy positive emotions, then we need an intervention that can address this mechanism. And to that end, I developed Mindfulness Oriented Recovery Enhancement, or MORE, just an integrative therapy that unites complementary aspects of mindfulness training, cognitive behavioral therapy, and principles from positive psychology into a treatment that can simultaneously address addictive behavior, emotional distress, and chronic pain. And before going on further, I want to just operationalize this term mindfulness for you. I'm sure you've all heard about mindfulness. It's sort of everywhere nowadays, and there's lots of different understandings of what this concept means. So let me offer you my understanding from the literature. So mindfulness is a form of mental training involving a mental training practice, also known as meditation, where one focuses your awareness and cultivates acceptance of your thoughts, emotions, and sensations in the present moment, and observing thoughts, emotions, and sensations as if you were a witness. So cultivating this capacity for meta-awareness. So the practice of mindfulness is pretty simple. We begin by focusing our attention on an object, it could be any object, but we often start by focusing on the breath. And then after a few moments, the mind begins to wander. Then we notice that the mind has wandered. And we don't beat ourselves up about it, we just acknowledge and accept that the mind has wandered off and become distracted. And then we let go of those thoughts and return the focus of the attention back to the object of mindfulness. And with each iteration of this loop, or this cycle, we're strengthening the mind's capacity for meta awareness, this ability to witness your own mental process. And I would also add here that mindfulness is not a mere relaxation technique, but rather, it actually operates by strengthening attentional control, emotion regulation and self-awareness. So with mindfulness-oriented recovery enhancement is a sequence treatment. It begins with the foundation of mindfulness training, which aims to strengthen attentional control and meta awareness. And these capacities are used to synergize more elaborate therapeutic techniques like reappraisal and savoring, and ultimately lead towards self-transcendence, the sense of being connected to something greater than the self. These treatment components are intended to modulate a series of therapeutic mechanisms that are in turn intended to produce clinically significant change in the range of treatment targets relevant to chronic pain, opioid misuse and opioid use disorder. And I would add here that MORE has been tested as a treatment for a wide array of addictive behaviors. But today, this talk is really going to focus on MORE as a treatment for opioid misuse and addiction. MORE is typically delivered as a group therapy over eight sessions. Sessions are two hours long, typically, they begin with a formal mindfulness meditation exercise followed by debrief and group process, which is just exquisitely important in helping patients to consolidate what they've learned from the mindfulness experience and then apply it to alleviating their symptoms of addictive behavior, emotional distress and pain in everyday life. After the group process, new psychoeducational material is delivered with the session topics listed here on the left. And then sessions end with an experiential exercise, some sort of mind body technique to hammer home the concepts that you've been teaching in psychoeducation. And then participants are asked to practice homework consisting of 15 minutes of mindfulness reappraisal and or savoring practice a day. Patients are also asked to stop before they take their opioids or other drugs or before they use medication assisted treatment methods like methadone or buprenorphine and to practice three minutes of mindful breathing. And this technique is intended to help the patient to clarify whether their opioid use is being driven by pain relief or driven by other factors like craving. It's also intended to prevent unnecessary opioid dosing by providing a non opioid means of pain relief. And in the case of a patient receiving medication assisted treatment, this technique can actually increase one's commitment to MAT. So this technique, we call it the stop technique, it's quite simple. The first step is to S stop right before you take your medicine or drugs. Then T take a few minutes to practice mindful breathing, calm down the mind, calm down the body, or reduce physiological activation. Then O observe your thoughts, feelings and body sensations in while you are holding the pill in front of your face or while you are about to use the drug. And during this process, become aware of how your attention starts to become distracted by the sight of the drug. That's the attentional bias that I was talking about earlier. Notice how craving might begin to arise in the mind or the body. Observe that it's possible to have an urge, but you don't have to give into the urge. And then return the focus of your attention back to the breath if you need to calm yourself down and recenter yourself. And the final step in the stop technique is P to proceed with intention. If the client does choose to take the drug, recognize that you're putting a powerful chemical in your brain and your body and that act deserves respect, attention and awareness. If you choose to take medication assisted treatment, contemplate how doing so is saving your life. So now I want to take a moment to talk about how we teach patients to cope with pain and more. So people with chronic pain typically experience pain as this monolithic, solid and overwhelming experience. It's this terrible, awful thing that always seems to be there. And on top of that, they overlay a layer of suffering, they say to themselves, why me? This isn't fair. This pain is ruining my life. And this emotional anguish actually amplifies pain processing in the brain. And more patients are taught a mindfulness technique to remove this emotional overlay, and then to decompose or break down the pain experience into its subcomponent sensations. So rather than focusing on some terrible, awful anguish in one's body, we teach patients to zoom in and to break that experience down into sensations of heat, or tightness or tingling, as well as to notice the spaces in between those sensations, where there's either no sensation at all, or potentially pleasant sensations right next to the painful ones. And using mindfulness to reduce emotional bias in this way may actually decrease the intensity of pain perception. And we use a very similar technique and more to help patients to cope with craving, teaching them to break the craving down into its cognitive, emotional and sensory components. Now I want to take a moment to talk about one of the techniques and more that makes this therapy quite unique. Patients and more are taught a mindful savoring technique here depicted in this beautiful infographic developed by the National Center for Complementary and Integrative Health for the more research program. Patients are taught to practice mindful savoring by focusing their attention on a on a beautiful flower, like a rose, using mindfulness to focus on and appreciate the pleasant colors, textures and scent of the flower, as well as the touch of its petals against the skin. And during this practice, patients are guided to cultivate a meta cognitive reflective attitude and to become aware of when positive emotions are arising in the mind, to become aware of when pleasant sensations are arising in the body, and then to turn their attention inward and to savor the pleasant inner feeling. Then patients are asked to practice this technique with naturally occurring pleasant events in their everyday life. And this technique is intended to amplify reward processing in the brain, boost positive emotions, elicit meaning in life and cultivate self transcendence, the sense of interconnectedness between the self and the world. And through this integration of mindfulness, reappraisal and savoring practices, more aims to modify associative learning mechanisms that have become hijacked during the allostatic process of addiction, by strengthening top down cognitive control to restructure bottom up reward learning from valuing drugs back to valuing natural rewards. And this therapeutic focus accords with my restructuring reward hypothesis, which states that shifting valuation from drug-related reward back to valuing natural rewards will reduce craving and addictive behavior. And in my view, not only as an addiction scientist, but also as a psychotherapist who's worked with patients with substance use disorders for about two decades, I feel that this process of restructuring reward learning is actually the essential process in addiction recovery. The person in recovery must relearn what is and what is not important in life, what is and what is not meaningful in life, and to reclaim that sense of meaning that was hijacked by the addictive process and then reinvest it back into the people, activities, and values that they once cared about. So I've given you a lot of theory about MORE, but let's get into the data. So MORE is an evidence-based treatment. This past year, a meta-analysis of all the randomized controlled trials of MORE was published and showed that MORE produced statistically significant effects in reducing addictive behaviors, psychiatric symptoms, and chronic pain relative to a range of control conditions. So let's just highlight some of these key studies now and then you can get a sense of what this therapy could do. So the first set of data I want to talk about comes from the first NIH-funded stage 2 randomized controlled trial of MORE as a treatment for chronic pain and opioid misuse. In this study, there are 115 chronic pain patients who had been taking prescription opioids for about 10 years. At baseline, three-quarters of the sample reported misusing opioids, and there were high rates of psychiatric comorbidity in this sample. In summary of the findings, MORE led to significantly greater reductions in pain-related functional interference and pain severity relative to a supportive group psychotherapy control condition. And pain interference measures how much pain has interfered with a person's general activity level, their mood, their walking, their work, their relationships, their sleep, and their enjoyment of life. We also found that MORE significantly decreased opioid craving, and this effect remains significant even after controlling the effect of MORE on reducing pain. So this told us that MORE appeared to be directly targeting the addictive impulse. And we found that MORE decreased the occurrence of opioid misuse symptoms consistent with an opioid use disorder. There was a 63 percent decrease in the MORE group compared to a 32 percent decrease in the support group. And I would add here that these data clearly show that our control condition in this study was an active treatment, but MORE was mo' betta. And sorry for the terrible dad joke, terrible pun here, but, you know, when you have a therapy called MORE, there's really no end to the puns you can make. There's always more and more. And in this study, we also measured hedonic dysregulation using the DOTPROBE task, and we found the first evidence in the scientific literature from a randomized controlled trial that a mindfulness-based intervention could reduce the pain attentional bias. So after eight weeks of training with MORE, patient's attention was less hyper-focused on, less captured by pain-related information. We also found that among patients with an opioid attentional bias at baseline, that MORE significantly reduced that attentional bias. So after eight weeks of treatment with MORE, patient's attention was less captured by, less biased towards, less triggered by the opioid-related cue. And recently, we replicated this effect in a much larger sample, showing the same effect that MORE significantly decreases the opioid attentional bias. So we're showing here that MORE is, again, decreasing the extent to which the patient's attention is being triggered by the drug cue. Some of the most interesting data that we got from this study came from heart rate collected during this task, and I don't think you really need to know much about statistics to see there's a big effect going on here. We found that across all three cue conditions of the DOPROBE task, that MORE led to significantly greater reductions in heart rate during the task. Not surprisingly, the more patients' heart rate slowed as they viewed the opioid and the pain images, the less aroused, the less stimulated they felt by those images. And that made perfect sense. But we found the opposite pattern in response to the pleasurable photographs. The more patients' heart rate slowed as they viewed the pleasurable photographs, the more aroused, the more stimulated they felt by those images. And we took this to mean that perhaps MORE was increasing physiological sensitivity to natural reward. We conducted a heart rate variability analysis and found that across the board, MORE led to significantly greater increases in heart rate variability than the control group, but the effects were most pronounced to the pleasure cue condition. So we wanted to understand the clinical implications of these findings, and we conducted a multivariate path analysis and found that the effect of MORE on reducing opioid craving was statistically mediated by changing the heart rate response to the pleasure cues, not by changing the heart rate response to the opioid cues. So these data told us that MORE was reducing opioid craving in part by enhancing sensitivity to natural pleasure, enhancing physiological sensitivity to natural pleasure. And this represented the most significant scientific finding of my career to that point. I think you can appreciate this if you remember that the prevailing neuroscientific model of addiction, the allostatic model, states that as a person becomes more and more addicted, their brains become less sensitive to natural healthy pleasure, and then that drives them to take higher and higher doses of the drug to feel okay. These data suggest that that process might actually be reversed, that by teaching people to become more sensitive to natural healthy pleasure, that might reduce craving and addictive behavior. And it was this finding that really allowed me to crystallize my restructuring reward hypothesis. In this study, we also collected ecological momentary assessments. So patients were asked to rate their pain and their mood every time they took their opioids up to four times a day across treatment. So this gives you a tremendous amount of data, about 224 data points per person, and we found that more was decreasing pain from moment to moment in everyday life. We also found that more was increasing positive emotions from moment to moment in everyday life. In fact, patients and more had 2.75 times the odds of those in the control group to be positively emotionally regulated over the course of therapy. And interestingly, it wasn't the decrease in pain that predicted the reduction in opioid misuse, but rather patients who showed the largest increases in the trajectory of positive emotions from moment to moment in everyday life showed the greatest decreases in opioid misuse. And this provided additional support for my restructuring reward hypothesis. All right, so let's take stock. What do we know? We see that more appears to decrease addictive behavior, craving, and drug acuity activity. And at the same time, more appears to decrease pain, but more also seems to increase positive emotions and enhance natural reward processing. So given these promising findings, we wanted to replicate them by conducting a second stage two randomized controlled trial of more. This one was done in primary care. And again, we found that more led to significantly greater reductions in pain severity and in opioid misuse by a three-month follow-up point compared to a supportive group psychotherapy. We also found that more increased an array of positive psychological functions, including positive emotions, savoring, meaning in life, and self-transcendence, the sense of being connected to something greater than the self. And importantly, the effect of more on reducing pain severity and opioid misuse was statistically associated with increases in these positive psychological functions. So it appears as if teaching people how to savor natural healthy joy, meaning, and self-transcendence may actually help to treat the disease of despair of opioid misuse. And in this trial, we also found that more significantly reduced opioid use. There was a 32% decrease in opioid use in the more group by the three-month follow-up point. We wanted to understand how more was producing these effects, so we brought patients into the lab and asked them to practice mindfulness meditation while we recorded their heart rate variability. And we found that the effect of more on reducing opioid use was statistically mediated by increases in heart rate variability during mindfulness meditation. This finding is interesting given that heart rate variability is a well-known biomarker of self-regulation or self-control. For example, in this experiment by Segerstrom and Ness, they presented participants with a tray. On one side of the tray had some gooey chocolate chip cookies. On the other side of the tray had some carrot sticks. And in one experimental condition, they told participants, resist your urge to eat the cookies, just eat the carrot sticks instead. In the other experimental condition, they told participants, you can eat the cookies if you want. When patients had to resist the urge to eat the cookies, they showed an increase in heart rate variability. So potentially, that's what we're seeing here as well, that more is actually facilitating reduction in opioid use by teaching people how to self-regulate their autonomic response with mindfulness meditation and thereby overcoming the urge to take opioids. And at the same time, we were interested in whether more could enhance outcomes among people with opioid use disorder who were being treated with medications like methadone. So in another NIH-funded trial, principal investigator was Nina Cooperman, we studied more as an adjunct to methadone treatment in New Jersey, actually in inner city New Jersey, in a predominantly African-American and Latinx group of patients. We didn't expect to see a statistically significant effect in this pilot study, but actually we did. We found that more led to significantly fewer days of opioid use, significantly fewer days of drug use, as well as less chronic pain and lower depression in patients who received methadone treatment as usual. And in this study, we also collected ecological momentary assessments. So we used smartphones and we pinged people a couple of times a day to rate their craving and their mood state. And we found that more was decreasing the strength of opioid cravings by 50% by the end of treatment, so cutting it in half. We also found that more was increasing positive emotions from moment to moment. And once again, we found that increases in positive emotions from moment to moment predicted decreases in opioid craving, providing additional support for my restructuring reward hypothesis. And now I've got the pleasure to present to you some hot off the presses data. This is from our follow-up study, an R33 funded study from the National Institutes of Health, basically the same design, but making it larger. And here we found in this replication study that patients treated with more that was delivered actually through telehealth, through Zoom, that more led to significantly fewer days of drug use than methadone treatment as usual. And patients in more had significantly longer time to relapse back to drug use than patients receiving methadone treatment as usual. More also increased adherence to methadone treatment. There was a greater number of patients who were still taking methadone at the 16-week follow-up compared to those in methadone treatment as usual. So really exciting. These data show that more appears to be an efficacious treatment for patients with opioid use disorder who are being treated with methadone. So let's take stock. What do we know? We see here that more appears to decrease addictive behavior and craving and to decrease pain. But at the same time, more appears to increase positive emotions and a sense of meaning in life. And these effects appear to be linked with increases in the capacity for self-regulation as well as access to self-transcendent experiences. So given all of these compelling findings, we wanted to start getting under the hood and understanding the neurophysiological mechanisms by which more was producing its clinical outcomes. So in a new sample of opioid-treated chronic pain patients, we brought them into the lab and they participated in an opioid cue reactivity task where they viewed opioid images on the computer screen while we measured their brain activity with EEG. And here in the red line, you can see the brain's response to viewing opioid cues before treatment more. Here in the blue line, you can see the brain's response to viewing opioid cues after eight weeks of treatment with more. So you can see more decreased the brain's reactivity to the opioid cue. And on the right, you can see brain waves from patients undergoing supportive group psychotherapy. Here you really see no real difference at all from pre to post treatment. And if you have trouble reading the squiggly lines, here's a bar chart that shows the effect. A massive decrease in brain drug cue reactivity produced by more. These are the first evidence from the scientific literature from a randomized controlled trial showing that a mindfulness-based intervention can reduce drug cue reactivity in the brain. And given the novelty and clinical significance of these findings, they were published in the top journal of science advances a couple of years ago. But in another randomized mechanistic study involving veterans with opioid-treated chronic pain, we found that more significantly increased neurophysiological responses in the brain as well as skin conductance responses during viewing and savoring of natural reward images, indicating that more is increasing the brain's sensitivity to natural pleasure. And we found that more also increased positive emotional responses while the patient was viewing naturally rewarding images of beautiful sunsets, lovers holding hands, smiling babies. Patients just who were treated with more felt happier after being treated with more and when they viewed these images. And the effect of more on reducing opioid misuse was statistically mediated by increases in these positive emotional reactions, again providing support for my restructuring reward hypothesis, which states that helping people to shift from valuing drug-related rewards back to valuing natural healthy rewards will reduce addictive behavior. And so this brings me to the largest randomized controlled trial of more ever conducted. It's my honor to talk to you about this study today. This trial was published in the top medical journal JAMA Internal Medicine last year. This was a five-year randomized controlled trial funded by the National Institute on Drug Abuse. In this trial, there were 250 chronic pain patients, all of whom were prescribed opioids and all of whom were misusing opioids at the time of enrollment into the trial. The sample average pain level was a 5.5 out of 10. They had been in pain for about 15 years. They were taking high opioid doses at baseline, about 100 morphine milligram equivalents a day. They had multiple chronic overlapping pain conditions, including low back pain and osteoarthritis, fibromyalgia, really any type of pain under the sun. And there were high levels of psychiatric comorbidity in this sample. Nearly 70% met criteria for major depressive disorder, 62% met criteria for opioid use disorder, full-blown opioid use disorder, 21% had a non-opioid substance use disorder, and there were high rates of generalized anxiety and PTSD as well. And these participants were randomized to receive eight weeks of more or eight weeks of a supportive group psychotherapy control condition. And we delivered these treatments in primary care in the same doctor's offices where patients were receiving their opioid pain management. In summary of the findings, using an objective index of opioid misuse that triangulates self-report, blind and clinical interview, and drug urine screen, we found that the effects of MORE on reducing opioid misuse were more than twice as large as those of the supportive psychotherapy control. Actually, the odds ratio at the nine-month follow-up was 2.94, so MORE was nearly three times as effective as standard group therapy at reducing opioid misuse. We also found that MORE significantly decreased opioid use through the nine-month follow-up point. So the 36% of patients were able to cut their opioid dose in half or greater. And this is really remarkable because we didn't push patients to taper their dose. They just decreased their dose on their own as a result of learning the skills in MORE. And we found that MORE significantly decreased craving from moment to moment in everyday life. So taken together, these data clearly demonstrate MORE's efficacy as a treatment for opioid misuse. At the same time, MORE significantly decreased chronic pain symptoms and emotional distress. 50% of patients treated with MORE reported clinically significant reductions in pain. And the effects of MORE on reducing chronic pain were larger than those observed for the current gold standard psychological treatment for chronic pain, CBT. And MORE also improved multiple dimensions of psychological health through the nine-month follow-up point. For example, MORE had powerful antidepressant effects. At the beginning of the study, nearly 70% of patients met criteria for major depressive disorder. But nine months after being treated with MORE, on average, patients no longer had depression symptom severity surpassing the threshold for major depression. MORE also led to significantly greater reductions in PTSD symptoms and supportive psychotherapy. 45% of patients who met criteria for PTSD showed a clinically significant decrease in PTSD symptoms. And MORE enhanced positive emotions, the sense of meaning in life, and self-transcendence. And these data provide support for my mindfulness to meaning theory, which states that mindfulness, reappraisal, and savoring stimulate an upward spiral of positive cognition and positive emotion to promote meaning in the face of adversity and enhance human flourishing. And these data really suggest that MORE is a broad-spectrum treatment that can simultaneously address addictive behavior, chronic pain, and the psychiatric conditions that are often comorbid with these issues. And we recently replicated these effects in another large randomized controlled trial funded by the Department of Defense. In this study, there were 230 past and current military service members, all of whom had chronic pain and were taking long-term opioid therapy. Patients were in pain for about 20 years on average and were taking on average 107 morphine milligram equivalents a day. And through an eight-month follow-up point, again, MORE outperformed supportive psychotherapy in reducing chronic pain symptoms and opioid dosing. So there was a 20.7% reduction in opioid use in the MORE group compared to a 3.9% reduction in the control group. And MORE also improved anhedonia, pain catastrophizing, positive affect, and opioid craving. But in addition to these clinical effects, MORE also appears to strengthen internal natural reward responses. So this is a computerized body map, and on this body map, patients locate pleasant and unpleasant sensations. Pleasant sensations are represented in blue. Unpleasant sensations are represented in red. The density of the hue indicates the frequency with which a given part of the body was identified as feeling pleasant or unpleasant. And this is a one-sided body map, and this is a one-sided body map, so it represents sensations on the front and the back of the body. And you can see here that MORE massively increased pleasant sensations in the body and powerfully shifted the ratio of pleasant to unpleasant sensations. So before treatment, patients reported experiencing about one pleasant sensation for every four unpleasant sensations. And I find that really sad. It just speaks to how much these folks were suffering. But by six months after being treated with MORE, patients reported experiencing two pleasant sensations for every one unpleasant sensation, indicating that more radically shifts the sense of one's body from being a place of anguish to becoming a place of refuge. These data also suggest that more teaches people how to self-generate natural, healthy, internal reward responses. So finally, we wondered whether experiences of self-transcendence evoked during deep meditative states might help to reduce addictive behavior. So in a recent mechanistic experiment published in the journal Neuropsychopharmacology, we found that veterans with opioid-treated chronic pain participating in MORE reported increased self-transcendence that was associated with increases in frontal midline theta, EEG, activity during meditation. So we found that the effect of MORE on reducing opioid use was statistically mediated by these increases in frontal midline theta, EEG activity during meditation. And again, the deeper the person was able to, or excuse me, the more intensely they were able to produce this increase in frontal midline theta, EEG activity, the deeper the meditative experiences they had, the more likely they were to report having this experience of self-transcendence, of being connected to something greater than the self. Now frontal midline theta is a well-known biomarker of cognitive control, but it also increases during states of flow, when the sense of self is suspended and transcended during deep cognitive absorption with ongoing experience. So these findings suggest that mindfulness meditation practice might actually produce a form of endogenous theta stimulation in the prefrontal cortex. In other words, helping patients to self-stimulate their theta activity in the prefrontal cortex, and thereby enhancing self-control over addictive behavior. And we recently replicated these results in the largest neuroscientific study of mindfulness as a treatment for addiction ever conducted. This study was published in the top journal of science advances a few months ago. In this study, there were 165 chronic opioid users randomized to MORE or supportive group psychotherapy. And again, we brought them into the lab and asked them to practice mindfulness meditation while we recorded their EEG. And you can see here without really knowing any statistics at all, that there's something really big going on here. I'd like to play this game. Which one of these four images here is not like the other? Clearly it's this image, and this is the brain activity following eight weeks of treatment with MORE. So you can see here that MORE massively increased theta oscillations in the midline regions of the brain. And increased frontal midline theta activity was once again associated with deeper states of self-transcendence. And the effects of MORE on reducing opioid misuse through a nine-month follow-up were statistically mediated by increases in this frontal midline theta activity. So replicating these effects across two independent samples and two independent randomized controlled trials tells me that we may have indeed found a very important mechanism by which mindfulness treats addictive behavior. So to summarize, we see now clearly that MORE is an efficacious treatment for reducing addictive behavior and craving. And at the same time, MORE decreases physical and emotional pain. But MORE also is an effective means of increasing positive emotions, natural healthy reward, and the sense of meaning in life. And MORE appears to produce these therapeutic effects by strengthening self-regulation and eliciting experiences of self-transcendence. So taken together, this body of work supports my restructuring reward hypothesis, which suggests that increasing natural healthy pleasure, joy, meaning, and transcendence may come to outweigh the pull of drug-related reward and thereby reduce addictive behavior. So given all of these indications of MORE's clear efficacy, it's time to disseminate this thing and implement MORE throughout healthcare, particularly to help treat people with opioid misuse and addiction and help to alleviate the opioid crisis. So I'm dedicating a lot of my career at this point to disseminating the intervention, to training clinicians and training agencies and health systems in this approach. And currently, MORE is being implemented in multiple healthcare settings, including addictions treatment, community mental health, oncology, pain management, and primary care. I think primary care is actually a particularly promising venue for implementation because MORE can simultaneously address the substance use disorders, psychiatric disorders, and chronic pain conditions that tend to show up in primary care, the so-called high utilizers. And MORE can and is being delivered as an insurance reimbursable medical group visit by physicians, nurse practitioners, and social workers and psychologists working in the primary care setting. I think another approach to implementing MORE is to deploy brief scalable techniques that we extract from the MORE intervention and then to use these techniques in standard medical care pathways, for example, in orthopedic surgery or patients in inpatient stays in the hospital. And we're finding that even a single 15 minute use of the MORE technique can produce significant benefits for alleviating acute pain, anxiety, desire for opioids, et cetera. But in conclusion, MORE is an efficacious treatment for addiction, stress, and chronic pain, as demonstrated by nine randomized controlled trials involving more than 1,000 patients. We've learned a lot about how MORE works over the past 10 years. MORE's mechanisms of action include reducing drug Q reactivity, enhancing natural reward processing, boosting meaning in life, and eliciting experiences of self-transcendence. And as I indicated, I'm really focused now on disseminating MORE. I train more than 700 physicians from around the U.S. and internationally, including social workers, psychologists, nurses, physicians, physical therapists, and I really want to see more of this work happening across the country. But ultimately, teaching people to take in the good and mindfully savor natural healthy pleasure may provide the learning signal needed to restore adaptive hedonic regulation and ultimately to reverse addiction. And I know that's a bold claim, but we're facing a serious crisis in this country, so we need bold solutions. And I sincerely hope that my work has in some way helped to address this crisis. So I want to thank you for your attention. I want to acknowledge the funders of my work, including the National Institutes of Health and the Department of Defense. I want to acknowledge my colleagues at the Center on Mindfulness and Integrative Health Intervention Development. And I want to point out, I'm holding more trainings for clinicians. The next one will be held by Zoom in July 2023, that's July 6th and 7th. So if you're interested in getting training for yourself or your agency or your healthcare system, just reach out to me and I'll give you more information. But now I'd love to take your questions. Well, hello, this is Kathy again, and I just want to thank you, Dr. Garland. That was fascinating. I can't wait to get some training myself. So one thing, we're going to do some question and answer, and if you would use the Q&A button down in the bottom. But before we start with those questions, I just want to make sure that to let you know that you will receive a survey via email tomorrow to complete, and then a certificate for the continuing education will be sent to you. All right, so let's get to the first question. And I think you just answered it on this slide, but it is where can we get specific training for this? Yes, thanks for the question. So I conduct a couple of trainings a year. I conduct trainings online by Zoom. That's a two-day training, 13-hour training that involves direct skill practice. There's some didactics and lecture, but a lot of it is practicing the mind-body skills and more, and then receiving feedback and delivering those skills, doing that in role-play exercises and getting real-time coaching. So that approach works really well. I also do go to agencies, health care agencies and clinics to provide this training if there's enough clinicians who are interested in getting trained. So I do both of those types of formats. Okay, the next question is, what is the demographics of the participants in the MORE studies? What percentage is composed of Native Americans? Great question. So actually, I'm pretty proud of this fact that we've done pretty well in terms of, generally in terms of diversity across the MORE research program. About 30% of the participants of the participants have been from non-white groups, from underrepresented groups. And so I feel like we've done pretty well. We can definitely do better, but we do have data on MORE as a treatment across a wide array of the ethnicities and races. That being said, we have not to date studied MORE in large numbers of Native Americans. So I think that percentage is pretty small. I think maybe 1%, 2%. I'm really interested actually in adapting MORE as a treatment for Native American communities. And I think that some of the values and potentially even the spiritual focus in the MORE intervention might resonate with some Native communities. But I don't want to presuppose anything, but I have spoken with a few folks from different tribes and they seem to think what I've heard is that there might be some overlap. And so I would be excited to explore that application. Okay. Thank you for that answer. The next question, often people receiving medication-assisted therapy for opioid use disorder also misuse other substances. Did you look at any impact on other substances in addition to opioids? Yes. So actually in the the replication study of MORE for patients receiving methadone treatment in New Jersey, we looked at effects of MORE on days of drug use of all drug types and relapse back to drug use of any kind of drug use. And MORE was producing significant therapeutic effects. So it's reducing drug use overall to a greater extent than methadone treatment as usual. So I think it's got some real promise there as a treatment for a wide array of addictive behaviors. And I'm particularly interested actually in whether MORE might be useful in in the treatment of stimulant use disorder like methamphetamine, because we all know that that's the next that's the next opioid crisis is the meth crisis. So MORE work needs to be done there. Okay. Would you please say more about how embodiment and somatic awareness slash movement is used in the teaching and training approach of MORE? Yes. So simply put, MORE is highly focused on embodiment and somatic awareness when we're doing our mindfulness practices, in particular around the issues of chronic pain. As I indicated, we're teaching people to use the focus of the mind to actually to zoom into the pain sensation. So to go right into the sensations in the body. And actually what we found is in enhancing the somatic awareness or interoceptive awareness, becoming more aware of the sensations themselves, actually it alleviates the pain and the distress. There is no movement aspect to MORE. So there's no yoga, there's no exercise. And those are opportunities, I think, to actually strengthen the MORE intervention. And actually there are a number of groups right now that are studying MORE integrated with physical therapy, both for patients with chronic pain, but also those who are using opioids. And our hope is that if we combine mindfulness with some physical exercise and physical activity, that will even get better effects. Okay. Thank you for that. Now, this one I can kind of answer. Is it possible to get this slide presentation? There is a PDF, or after this presentation, there will be a PDF copy of the slides on the PCSS website, and along with the copy of this videotape. Okay. And I know we already answered that one. Is there a place to review the Myriad Brief Scalable Techniques? How-to instructions to implement in clinic? Yes. So we've published several papers on that, on the use of our brief mindfulness techniques. Those to date have really been in, for patients in acute pain in the inpatient hospital setting, and then also patients going through orthopedic surgery. So those results have been published. One of those papers was published in the Journal of General Internal Medicine. The other was published in the Journal of Pain, and there was a follow-up paper that was published in the Journal of Consulting in Clinical Psychology. So if you're interested, just reach out to me, and I'll send you the papers, and I can send you the script for the brief mindfulness technique. What we don't know yet is whether, and by the way, the data is really clear that the brief mindfulness is actually dropping pain quite a bit, dropping pain by about 25%. What we don't know yet is whether a very brief mindfulness technique would be reduced, would be useful for treating addiction. So that's future work that we have to do. Okay. And then someone else wants to know if you have any results with THC overuse? Yes. In fact, again, in the study of more for patients on methadone, one of the drugs that patients were using was cannabis, and we did find that more significantly reduced days of cannabis use. This person said they signed in a little late, but they want to know what method you are using but they want to know what method you are using pinging the client? Yes. So that's referring to the ecological momentary assessment studies. So we were pinging their smartphones. So they were getting random probes a couple times a day to ask them to rate how they felt, their pain level, their mood state, their craving, et cetera. Okay. This one asks, there's so little information about opioid use disorder in adolescents and young adults. Have you evaluated the results in young adults? And then she says, our sickle cell population needs this. This is a great, great point. We have not evaluated more in people under the age of 18, but we certainly have had a number of folks, young adult folks, 18, to 25, 24, they seem to respond quite well to more. We haven't had a study to specific study in that population, but there's always been a proportion of our patients who fall into that age range. I totally agree about sickle cell. And I think that more is, would be a promising treatment for patients with sickle cell. So I'd love to see it applied in that domain. Okay. Has there been any research completed on opioid use disorder in young adults? Has there been any research comparing more and ACT? Good question. Short answer, no. So we've never compared more to ACT. That would definitely be an interesting comparison. There's obviously a lot of overlap between the two therapies, and then there's some clear differences as well. Someone else is wanting to know if there are findings related to gender differences. Great question. The short answer is we need to do more work in that area. I can tell you that, I can't tell, I can't speak across studies as a whole. I can tell you that within some of our studies, we do find differential effects of more on pain in men and women, but we really need to do more research in that area. And I'm hoping now that we've finished these really big clinical trials, we can start to combine the data and then to start to look at subgroups to see how different genders respond to more, different racial groups respond to more, how people with different pain conditions respond to more. So we need to learn more about that. Okay. And this one's been surfing here asking, your website says summer of 2023. Are there any definitive dates? I remember you talked about July, was it 6th and 7th? That's right. Good memory. Yeah. I just set the dates actually yesterday. So July 6th and 7th will be the next training. So they'll be on your website soon then? Yes. Okay. And is more in the same as positive psychology and the work and research out of the University of Pennsylvania? Is it the same? No, but more does involve a positive psychological focus. And that piece of it is similar to the work at the University of Pennsylvania, where the two places where positive psychology really show up in more, one is in the savoring technique where we're teaching people how to focus on naturally rewarding, pleasant experiences in everyday life as a way to amplify positive emotions and pleasurable sensations in the body. The other place where positive psychology shows up is in teaching people how to engage in positive reappraisal. So to find meaning in the face of the adversity in their lives. Okay. I think we have time for one more question. So is there any data on the effect of MORE on alcohol abuse? The very first clinical trial of MORE was conducted in patients with alcohol use disorders. That was my dissertation actually. It was published in 2010. And this was a sample of patients who were inpatient. And so there really wasn't much relapse because they were inpatient. They were inpatient. So we couldn't really evaluate MORE on drinking because these folks were abstinent. But what we did do is we actually showed them images of alcohol on the computer screen, and then we measured their heart rate response. And we found that after the MORE therapy, patients' heart rates were able to recover to a greater extent after we triggered them with the alcohol cue. So we saw some evidence that MORE actually helped people to be less reactive to alcohol cues. And that told us that maybe MORE would be useful in treating alcohol use disorder. We actually haven't followed that up with another study focused specifically on alcohol, but given the positive effects we're finding on drug use, I'd be willing to bet that MORE would be useful in helping people to cut down their drinking. Okay. I think that's all the time that we have. I'd just like to thank you again for this fantastic presentation. I'm glad to see our government money going to things like this that are very, very much needed. So I appreciate it. Thank you. Thanks to all of you. And if you have questions, please shoot me an email. I'm happy to connect with you. Bye.

Dr. Eric Garland

Mindfulness Oriented Recovery Enhancement

University of Utah College of Social Work

cognitive behavioral therapy

neuroscience

addiction

chronic pain

opioid misuse

randomized controlled trials

dissemination and implementation