To continue the spirit, let's welcome our next mini-symposia, Mindfulness and Opioid Use Disorder, Primary Outcomes of Five RCTs with Effects on Substance Use, Craving, Pain, Mental Health, and Potential Mechanisms. It's chaired by Dr. Zev Schumann-Olivier. Dr. Schumann-Olivier is an assistant professor of psychiatry at Harvard Medical School and a board-certified addiction psychiatrist. He is the director of addiction research and founding director of the Center for Mindfulness and Compassion at Cambridge Health Alliance. He is a faculty affiliate of Center for Technology and Behavioral Health, a NIDA-funded Center of Excellence at Dartmouth. He previously served as a medical director for outpatient addiction services and also as a director of addiction psychiatry residency at Cambridge Health Alliance for five years. He has been involved in clinical care of patients with chronic pain, substance use, and mental health disorders, both in mental health, primary care, and addiction recovery setting. With a unique research focus on behavioral interventions like mindfulness and compassion-based interventions. He is also a chair of our new special interest group on integrative and complementary medicine. With that, I welcome Dr. Schumann-Olivier, who will then introduce the rest of the panel and present his data. Thank you. Thank you for that lovely introduction. I'm really happy to be here and so glad to be here with all of you. So just all relevant financial relationships have been mitigated and we have nothing else to disclose. I want to say that we're very grateful for the support from NIDA, from NCCIH, in particular the Science of Behavior Change and the HEAL initiatives and the BRIM initiatives to be able to support the work that you're going to see today. This is work from grants that have been many years in the making. We hope at the end of the session that you'll be able to summarize the evidence base for mindfulness in treating opiate use disorder, be able to understand how mindfulness can address craving and other common OUD comorbidities. I hope you'll be able to understand and recall the definition of mindfulness and key factors for integrating mindfulness into medication for OUD treatment. And hopefully you'll also be able to identify some neurophysiologic and psychological mechanisms for mindfulness in opioid treatment and recovery. I'm going to start with a few definitions of mindfulness because you can turn on your radio or go down the supermarket aisle and see the word mindfulness everywhere and it's kind of started to mean just about everything. In this symposium, we're going to use a scientific definition of mindfulness and there are three different definitions that I think are appropriate to understand. So the first is from John Kabat-Zinn, you all may have heard of him. He is one of the founders of Mindfulness-Based Stress Reduction. And he defined mindfulness as the awareness that emerges through paying attention on purpose and non-judgmentally to the unfolding experience moment to moment. Bishop and Siegel defined mindfulness with two parts. It's regulation of attention, maintaining it on immediate experience, and approaching one's experiences with an orientation of curiosity, openness, and acceptance, regardless of the experience's valence or desirability. A definition that I've used and has been published in the literature is the capacity to warmly be with present moment experience as it changes from moment to moment. I want to separate out mindfulness and meditation. So meditation is the practice, is any practice that self-regulates the body and mind by engaging a specific attentional set. So one could have a meditation on a mantra and a word again and again, or could pay attention to a shape or a candle again and again, and returning back again and again, that is meditation. If what you are returning to again and again is some aspect of present moment experience and you're doing that with an orientation of curiosity, openness, acceptance, and being with what you're noticing without reacting to it, that is mindfulness meditation. So that's a bit about what we're talking about here today. So there are some early findings that I'm not going to go over too much, but you can have them here and look them up if you'd like. But people have found that there was less thought suppression among people with AUD after mindfulness training, decreased motor impulsiveness among people with opiate use disorder after mindfulness training. People were able to disconnect the negative affect, feeling bad, mad, sad, from craving. People were able to disengage attentionally from addictive cues and have less autonomic, faster autonomic recovery after cue exposure. And people have found that reducing craving in studies with substance use disorder can actually reduce the substance use. And that when you mindfully savor present moment experience and pleasant events, perhaps you can actually correct some of the reward dysfunction that is present in addictive disorders. There was a very important study in 2014 that I think opened up the door for the kind of work that we're doing today, and that was a mindfulness-based relapse prevention program, which was an eight-week program, versus relapse prevention alone. And that was published and found at 12 months that MBRP had fewer drug use days and fewer heavy drinking days. So I wanted to give them credit for that early work. Since that time, you can see there's been an explosion of mindfulness research in just in the last two years alone. Each year, there's been about 1,500 publications in PubMed each year that involves mindfulness. And our patients are picking up on this, and they're starting to experience it. In a survey study that was done, actually, Dr. Garland here was, I believe, the senior author on this paper, a survey of 72 patients in opiate treatment with buprenorphine at Bellevue in 2021 and 2022, 90% of patients reported practicing one category of meditation. We need to be paying attention to this as clinicians to understand what it is that our patients are doing. Fifty-five percent of those were actually practicing mindfulness meditation, second only to spiritual meditation or prayer. And people said that they were practicing in order to improve their general health and well-being, to reduce anxiety and depression, to deal with cravings for illicit substance use, and to even address their opiate withdrawal symptoms. So this is the culmination. This mini-symposium is offering the first presentation of the main outcomes of several RCTs of mindfulness and MOUD, funded by the NCCIH BRIM mechanism. And we're thrilled to have this here because the BRIM mechanism was founded because of some of the pioneering work that Dr. Weiss did that had actually demonstrated that many behavioral interventions were not showing an added above additional benefit to medications for opiate use disorder treatment. And this NIH program kind of set out to test some other novel behavioral interventions. So on that note, I'm going to introduce you to Eric Garland, who's a distinguished endowed chair in research at the University of Utah. He is a professor and associate dean for research at the College of Social Work. He's director of the Mindfulness and Integrative Health Intervention Development Program and associate director of integrative medicine at the Huntsman Cancer Institute. It's important to say that he is, he wouldn't say this himself because he's humble, but he is the, he's published more papers than anybody else in the field about mindfulness. So I just want to give you that props. And on that, I'll turn it over to you. Thanks so much, Zev. So the opioid crisis, which was driven in large part by the chronic pain epidemic, has been termed a disease of despair. And this term strikes right at the heart of the pathogenic mechanisms that are driving this crisis. 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 come to outweigh the experience of pleasure in everyday life. Neurobiology suggests that pleasure and pain operate through a common emotional currency in the brain, mediated by the mesocorticolympic dopamine circuit and the endogenous opioid system. And these same brain systems become hijacked by opioids through an allostatic process, in which chronic exposure to opioids causes neuroplastic changes that increase sensitization 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 if hedonic dysregulation is driving the downward spiral from chronic pain to opioid misuse and opioid use disorder, then we need interventions that can target this mechanism. And to that end, I developed Mindfulness Oriented Recovery Enhancement, or MORE, which is an integrative mind-body therapy that unites complementary aspects of mindfulness training, cognitive behavioral therapy, and positive psychology into a treatment that can simultaneously address addictive behavior, emotional distress, and chronic pain. MORE is a sequence treatment. It begins with a foundation of mindfulness training, which by virtue of strengthening attentional control and meta-awareness, is used to synergize more elaborate therapeutic techniques like reappraisal and savoring, and ultimately to lead to self-transcendence, the sense of being connected to something greater than the self. These treatment components are intended to activate a series of therapeutic mechanisms that are in turn intended to produce clinically significant change in a range of treatment targets relevant to chronic pain, opioid misuse, and addiction. I just want to highlight one of the techniques in MORE that makes it a little different than other therapies. In MORE, patients are taught a mindful savoring technique where they're guided to direct mindful awareness towards a pleasant object like a rose, attending to the beautiful colors, textures, and scent of the flower, as well as the touch of the petals against the skin. And during this process, patients are guided to cultivate a metacognitive reflective attitude, and to become aware of, appreciate, and amplify any positive emotions or pleasant sensations arising during the savoring experience. Then they're asked to practice this technique with everyday occurring natural pleasant events in their lives, and this technique is intended to amplify natural reward processing in the brain, boost positive emotions, elicit meaning in life, and cultivate self-transcendence. And through an integration of mindfulness, reappraisal, and savoring techniques, MORE aims to modify associative learning mechanisms that have been hijacked during the allostatic process of addiction by strengthening top-down cognitive control functions to restructure bottom-up reward learning from valuing drugs back to valuing natural rewards. And this focus accords with what I call my restructuring reward hypothesis, which states that shifting valuation from drug-related reward back to valuing natural reward will reduce craving and addictive behavior. So MORE is an evidence-based treatment. It's been tested in 12 randomized controlled trials, but I wanted to highlight two high-impact trials for you here today. The first was a NIDA-funded R01 project in this clinical trial, and the results of which were published in JAMA Internal Medicine last year. In this study, there were 250 chronic pain patients, all of whom were prescribed opioids and all of whom were misusing opioids at baseline. They were randomized to receive eight weeks of MORE or eight weeks of a supportive group psychotherapy control condition. Study interventions were delivered in the same doctor's offices where patients were receiving their opioid pain management. Patients were taking high opioid doses at baseline, an average of 101 morphine milligram equivalents a day. Three-quarters of the sample reported having two or more overlapping chronic pain conditions, and there were high levels of psychiatric comorbidity in the sample. For example, 62 percent met criteria for full OUD. In summary of the findings, MORE reduced opioid misuse by 45 percent at the nine-month follow-up point, nearly tripling the effect of standard group psychotherapy. MORE also significantly reduced opioid dosing and reduced opioid craving from moment to moment in everyday life, measured through ecological momentary assessment. At the same time, MORE reduced chronic pain symptoms and emotional distress, and the effect sizes we observed for MORE in reducing chronic pain exceed the meta-analytically derived effect sizes for CBT, the current gold standard psychological therapy for chronic pain. But MORE also improved an array of psychiatric symptoms. At the beginning of the trial, nearly 70 percent of patients met criteria for major depressive disorder. But by nine months after being treated with MORE, patients' depression symptom severity level no longer surpassed the threshold for major depression. MORE also reduced PTSD symptoms significantly. Fifty-nine percent of patients who surpassed a cut point for PTSD on the PCL reported clinically significant reductions in PTSD symptoms. And at the same time, MORE improved positive emotions, meaning in life, and self-transcendence. So these data 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 problems. But we recently replicated these results in a DOD-funded clinical trial to target chronic pain and opioid use among veterans and military personnel. Halfway through this trial, COVID struck, and so we had to rapidly pivot to delivering MORE through telehealth. In this study, once again, MORE outperformed supportive group psychotherapy through an eight-month follow-up in reducing chronic pain symptoms and opioid use. There was a 21 percent reduction in opioid use in the MORE group compared to a 4 percent reduction in the support group. While both treatment conditions significantly reduced opioid misuse, in the in-person cohorts, MORE outperformed supportive psychotherapy. And MORE also led to significant decreases in opioid craving, pain catastrophizing, and anhedonia while increasing positive affect. So given MORE's clear clinical efficacy as a treatment for opioid misuse and chronic pain, we wanted to understand the neurophysiological mechanisms of this treatment. So in a randomized mechanistic experiment, we brought patients into the lab and had them participate in an opioid Q-reactivity task while we measured their brain activity with EEG. And we found that MORE led to significant and robust decreases in brain drug Q-reactivity. This is the first evidence from a randomized controlled trial in the scientific literature that a mindfulness-based intervention can reduce drug Q-reactivity in the brain. And in a separate randomized mechanistic experiment, we found that MORE significantly increased EEG and skin conductance responses during viewing and savoring of natural reward cues. The effect of MORE on reducing opioid misuse was statistically mediated by increasing responsiveness to natural healthy rewards, providing support for my restructuring reward hypothesis. But more recently, we wondered whether deep meditative states might also have anti-addictive properties. So in the largest neuroscientific study of mindfulness as a treatment for addiction, we brought patients into the lab and asked them to practice mindfulness meditation while we recorded their brain activity with EEG, both before and after treatment. We found that MORE led to massive increases in frontal midline theta EEG power and coherence. Higher levels of frontal midline theta were associated with more intense self-transcendent experiences and mediated the effect of MORE on reducing opioid misuse through a nine-month follow-up point. These data suggest that mindfulness meditation may provide a means of endogenous theta stimulation of the prefrontal cortex and thereby strengthen inhibitory control over opioid use. So taken together, these data support my restructuring reward hypothesis, suggesting that increasing healthy pleasure, meaning, and self-transcendence may come to outweigh the pull of drug-related reward and thereby reduce addictive behavior. In summary, MORE demonstrated efficacy in two full-scale randomized controlled trials for reducing opioid use and misuse, chronic pain, craving, and psychiatric symptoms. MORE's mechanisms of action include reducing drug Q reactivity, increasing natural reward processing, strengthening self-regulation, and eliciting self-transcendence. In these trials, it's clear that MORE outperforms supportive group psychotherapy, but we don't know whether MORE is superior to other evidence-based practices like cognitive behavioral therapy. Nonetheless, given MORE's clear efficacy for treating opioid misuse and chronic pain, it's now time to disseminate this therapy. I've been really dedicated to this effort. I've trained more than 850 clinicians, including social workers, psychologists, nurses, and physicians from around the U.S. and internationally who are now delivering MORE as part of a clinical practice. 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. And I sincerely hope that this line of work has been helpful in that regard. So thank you. And now I'd like to introduce Dr. Nina Cooperman from Rucker's Robert Wood Johnson Medical School, Addiction Psychiatry. Thank you for the introduction. So Dr. Garland just presented the background of mindfulness-oriented recovery enhancement for people with chronic pain to prevent opioid misuse and in chronic pain settings. So I come from a background of working with people in treatment for substance use disorder. And I thought, well, given the efficacy of this intervention for people with chronic pain to prevent opioid misuse, what about using this in substance use treatment settings for people who have an opioid use disorder? So I reached out to Dr. Garland, and I said, well, can we evaluate this in this population? And that's what we did. So we applied for an R21, R33 BRM grant with NCCIH and the HEAL Initiative. This had never been evaluated before in a drug treatment setting. So we wanted to pilot it initially with a small group of people, and then once we determined feasibility to determine preliminary efficacy in a larger trial. So I'm going to describe these two trials for you today. So first, before I describe the trials, I just want to acknowledge the wonderful team of investigators and the clinics and the patients and the research staff that helped complete this study. So we know that medication for opioid use disorder is fundamental for treating people with opioid use disorder. And methadone is the most common medication for opioid use disorder. And in methadone settings, oftentimes individuals are receiving other types of psychosocial treatments as adjuncts, whether it be cognitive behavioral therapy, relapse prevention, motivational interviewing. But despite this, we also know that about 50% of people who begin methadone treatment discontinue within a year. And among those who are retained in treatment, they relapse or use drugs within six months. So there really is a need for something that's more effective. And so from my observations, I started thinking about something really transdiagnostic that is addressing the emotion dysregulation and the physical pain that is prevalent in this population and could be contributing to relapse and preventing recovery in this population. So we really need novel behavioral interventions to address these issues and to prevent opioid relapse in this population. So just to give you a little bit of overview of the more session content, I know Dr. Garland told you a little bit about the background of the MORE intervention and sort of the philosophy and how it works. This is a little bit more of the logistics of that. And how we implemented it in methadone treatment. So it's an eight-week group intervention. Each group is two hours long. It involves formal mindfulness meditation, experiential exercises of mindfulness meditation. And then a debrief of the process and of the experience. And there also incorporates psychoeducation and didactic material. And with the goal to have people practicing the skills that they're learning in the group outside of the group at home. So the goal is to have them practice 15 minutes of mindfulness, reappraisal, and savoring skills each day. And here you see the different topics for each session. It does build upon itself. It's a closed group. So each session, the material follows from the previous session. It incorporates a focus on physical pain and suffering and also emotional well-being. And one of the things that we incorporated into this version of MORE is a focus on actual the process of taking methadone with the hopes that it would improve adherence to the medication and a sense of awareness through the process of taking methadone. So we had, as I mentioned, two studies. The first study was a small pilot study just to determine feasibility. We randomized 30 people, 15 in mindfulness-oriented recovery enhancement group intervention and 15 in methadone treatment as usual. And then after that study, we did a larger study which I'll also tell you about of 154 people we randomized 77 to MORE and 77 to methadone treatment as usual. Just to tell you a little bit about the way these interventions and these studies happen. The first, the pilot study happened before COVID. So that was in person. We were just about to start the larger study when we had to pivot and COVID hit within weeks of us about to start that study. So we had to transfer it to telehealth and we implemented that study completely remotely. And we provided tablets to individuals for the second study so that they were able to ensure everybody was able to access the internet. We conducted both studies in several methadone clinics in New Jersey and we recruited participants through flyers, through referrals, through clinic staff, recruiting people in patient waiting areas. During the period of COVID, people were getting dosings from their cars as they were driving up. So we were handing flyers into cars. There was a lot more phone calling during that time. And once we recruited a block of 14 people since it was a closed group, we then randomized seven to MORE and seven to treatment as usual. And eligibility for the study was to be on methadone, experiencing chronic pain, and able to participate in the intervention. We conducted surveys at baseline, eight weeks, which was post-treatment, and then 16 weeks, which was eight weeks after completion of treatment. We gave everybody a smartphone during the pilot study and a tablet during the larger study so that they can complete a twice-daily ecological momentary assessments. Actually, it was three times a day ecological momentary assessments where we assessed drug use, craving, pain, and emotional state. The patient characteristics in both studies were basically similar. Most participants were about, on average, middle age, a little over half or half were female. We had a diverse sample that varied a little bit between the pilot and the larger study, but we had the diverse sample. Most were unemployed, and interestingly, a large percentage had actually been using drugs in the previous month before starting the intervention. And the most common pain conditions were arthritis and back pain. We didn't see any statistically significant differences between the intervention and the treatment-as-usual group in either the pilot study or the larger study. With the exception in the larger study, we did see in the intervention group more individuals had used drugs in the previous 30 days, so we did include that as a covariate in our analyses. So we were just looking at feasibility. We didn't expect to have statistically significant outcomes in the pilot study, but we did. So we found not only was the intervention feasible when implemented in person in the methadone clinics, we found that those receiving more reported significantly fewer days of heroin and other drug use than those in treatment-as-usual over the course of the 16-week study, and we published these findings in the Journal of Substance Abuse Treatment in 2021. Also, we found that those in more had significantly better pain-related functioning. Those in more had significantly less depression over the course of the study, and those in more had significantly less anxiety as well. So, and these were all statistically significant in our very small sample. So based on that success of that feasibility study and some sign that there is potentially an effect here, we went ahead with the larger R33 study where we enrolled 154 people. So we initially screened 219 for eligibility. We randomized 154, and we had a pretty good retention rate in terms of following people, especially given the COVID period. So we did everything remotely pretty much during this study. For the primary outcomes, we were looking at relapse. So number of days till the first drug use, and we were assessing this through EMA, self-report, or drug screens that we were abstracting from clinic charts. And we also wanted to look at methadone treatment retention. So did people stay in methadone treatment? And we assessed that through clinic reports. So if the clinics told us whether that person was still enrolled and still coming to treatment. We also wanted to look at days of drug use over the course of the 16-week period, and we created a variable that incorporated self-report, EMA data, and drug screen data. And we also looked at methadone adherence. We planned on measuring methadone adherence by looking at actual dosing at the clinic when we were planning to do this in person. Since people were dosing at home during the pandemic, we used a drug screen as positive for methadone at the follow-up visits as determining adherence to methadone. We also assessed physical pain through EMA. We'd ask people how intense your pain is right now on a scale from zero to 10 through three daily prompts over the 16 weeks, and we assessed depression and anxiety at follow-up visits and at baseline with the CESD scale and the back anxiety inventory. So the results. So we had really, really promising and interesting results. Participants and more had significantly less opioid or other, had significantly less relapse to opioids or other drugs. And when I say opioids or other drugs, I mean cocaine, methamphetamine, heroin, prescription opioids, marijuana, prescription opioids used illicitly or not as prescribed. And we did adjust for a priori specified covariates, and those covariates included the amount of clinic counseling time that individuals received in the clinic, not including more, and at baseline drug use in the past 30 days, the methadone dose and the amount of time that people were in methadone treatment. We also found that those in more were significantly less likely to drop out of methadone treatment over the course of the study. We found that those in the more intervention over 16 weeks had fewer days of drug use over the course of the 16-week study. We found that although methadone adherence was the same between groups at baseline and at eight weeks when we followed them through 16 weeks, those in more were significantly more likely to be adherent to the methadone than those in the treatment-as-usual group. We found that pain intensity, there were greater reductions in pain intensity over the course through EMA data among those in the more group as compared to treatment-as-usual. We found significantly greater reductions in depression among those in the more group as compared to treatment-as-usual. And interestingly, for anxiety, we found that although the reduction in more was not, the difference was not statistically significant, we did see a trend for increases in anxiety among those in the treatment-as-usual group while anxiety decreased among those in the more group. So, in conclusion, more demonstrated efficacy for addressing drug use, pain, and mental health and improving methadone treatment retention and adherence. So based on these results, we think some large-scale studies of this intervention are warranted. So we are now conducting some large-scale studies in methadone treatment to address chronic pain, opioid use disorder, and other polysubstance use, and that's what we're currently working on now. And if you wanna read more about this study, at this very moment, our article was released in JAMA Psychiatry. So, I invite you to take a look and learn out once more about our study. And now I'm gonna, back to Dr. Shuman-Olivia. Thank you. Congratulations, it's an exciting publication and a big, important step for the field. So I'm gonna talk now about the effects of live online mindfulness on opioid use, opioid craving, anxiety, and pain during buprenorphine treatment. The first presentation was about people with pain who are having opioid misuse. The second presentation was on mindfulness during methadone treatment. And now we're moving to buprenorphine treatment, which is one of the most common medications for opioid use disorder treatment. So the story starts back about 10 years ago now when we developed the Mindful Behavior Change curriculum. And this is funded by the Science of Behavior Change, NIH initiative. And if you wanna look up that paper, you can see some of the mechanistic, some of the mechanisms to which mindfulness impacts behavior change. What we set out to do was to iteratively refine an intervention that would engage in self-regulation to impact behavior change through increasing emotion regulation, decreasing experiential avoidance, which is the tendency to want to avoid discomfort or unpleasant experiences, to increase internal motivation for change, to engage self-related processes like interoception, which is the feeling of our internal body state, and increase self-compassion, decrease self-critical rumination, and increase attention inhibitory control. So the Mindful Behavior Change program that was developed was an eight-week program that had two hours a week originally. And what we had to do in putting this program together was to reconcile the non-striving with the need for change. And how do you recognize that when you need to make a change, let's say in chronic illness or an addiction recovery, that everything's always changing? What it would be like to step back and let it change? How do we allow change to emerge? How do we hold an aspiration for health, health behavior or for addiction recovery with just right way, like an egg? If you hold it too tight and you're too rigid about it, well, then you end up with an egg on the floor. If you hold it too loosely and you don't try and put effort into, then it ends up on the floor as well. So how do we learn how to hold our aspirations for change just right, and then set skillful goals so that if and when we do have a lapse or a slip, that we can treat ourselves with inner kindness instead of making global attributions like an abstinence violation effect. So we conducted three studies actually in primary care. This is with anxiety, people with chronic illness and anxiety, depression, or stress disorders. And I'm just gonna say that in these three studies, when we compared the eight week program to just an hour introduction to mindfulness, people repeatedly had around three times the odds of initiating a behavior change within three weeks of setting a goal if they went through the mindfulness training program. So we took that intervention and tried to bring it to primary care addictions treatment with buprenorphine. And this was actually a study that we did prior to the pandemic. This is an R21 with 18 people. It's a single arm proof of concept study. And what we found was that over 24 weeks receiving this intervention, that people had increased interceptive awareness. So they changed their relationship with their body and internal body sensations, increased mindfulness, self-compassion. They had less experiential avoidance. They were able to face discomfort and not avoid it or run away from it. And they had less anxiety and pain interference among those that had either anxiety or chronic pain disorders. And we also saw that cocaine and benzodiazepine use decreased over the 24 weeks through urine screening. So that set us up to say, let's go and try this intervention in a randomized control trial. So I'm not gonna get into all the complexities around what happened around COVID since we were supposed to start on May 14th, 2020 in Boston in primary care. And that was the day that everything shut down. So we had to transition to a national remotely delivered randomized comparative effectiveness trial. So we got folks, anybody who was already prescribed buprenorphine and we see over 24 weeks, if they would be randomized either to receive a live online mindfulness group versus a gold standard active online control group. We got a message from NCCIH that what they liked about our site design was that we were willing to put mindfulness up against the gold standard group-based opiate treatment. And look at outcomes like abstinence from illicit opioid use, effects on anxiety, pain, substance use and effects on craving for opioids. We only took people who had been on buprenorphine already for 30 days and had continued to have anxiety or other substance use. These are people who basically are post-buprenorphine induction but are unstable or struggling. And we didn't tell them that they were gonna get mindfulness because that can bias studies towards people that want and are looking for mindfulness. We told people that this would be a stress reduction study and we recruited people from 16 states. And when they started the groups, they then were in 60 minute stress reduction groups at the same time and went on for 24 weeks. And we tried to mimic the experience of being in a primary care clinic by having people come online 30 minutes before and check in and be able to talk and connect and get pulled in for oral fluid screening which we did in breakout rooms on Zoom which was the first time that I think at least that had been reported to do that. So the Mindful Recovery Opioid Care Continuum was what we called the intervention and we wanted to make it trauma informed and orient people slowly to mindfulness because we didn't want people to have negative traumatic reactions to it. So we had the first four weeks of the group orientation, supported them in getting curious about their experience, connecting with each other and getting confident about moving forward into a mindfulness program. Then we had four weeks where we slowly increased the dose of mindfulness to try to get people up to 20 minutes a day of practice through core mindfulness practice that were trauma informed. And then we gave people a decision in eight weeks. It was motivationally responsive. Do you want to continue and move into an intensive group or do you want to continue to utilize mindfulness in the community in ways that it can be available? And then we had a 16 week program based on the Mindful Behavior Change Curriculum specific for OUD. The groups basically had some didactic component, a check-in component, experiential practice and then it ended with applying what you learned that day to skills for daily life and informal practice. We tried to match everything very carefully between the groups. So we had an experienced mindfulness teacher who was a social worker, a female social worker who had four years of experience with mindfulness and we also, in order to build capacity, we had a co-teacher with them who was generally a new to mindfulness, either PCP, OBAD, RN or psychologist. But let's see, so then what was our control group? So we had an active control group and we tried to create a gold standard best practice group-based opiate treatment. This is citing Randy Sokol's work that she and I have been studying about implementing buprenorphine in group-based treatment experiences which is usually pretty good for encouraging retention in treatment. And so what we did was we had a manual that included motivational interviewing, cognitive behavioral therapy, community reinforcement approach and 12-step facilitation but explicitly had no mind-body or mindfulness references and it was focused based on Randy's paper around fostering a sense of accountability, shared identity and supportive community which had been found in previous work to be mechanisms to which group-based opiate treatment was helping patients. And we had a very successful group leader. They had four years previous experience and was the first person to direct a live online IOP in Massachusetts with high acceptability. So we started recruitment and immediately we were hit with the Delta wave and then the Omicron wave and you all remember how difficult that was. What we found was, so we recruited from 16 different states. The largest groups were from, as you can see there, Texas and Florida as well as California, Michigan, Massachusetts and North Carolina and we actually worked with some of these online buprenorphine providers like Bicycle Health and Boulder Care and we also sent out, maybe you all received a SAMHSA, a letter, because we sent it out in all these states to providers and we also used Facebook advertisements. We randomized 196 people to either the control or the mindfulness arm. People, 61% female, middle age, it was 92% white and 8% Hispanic. There was a high burden of trauma and childhood trauma in this population. 66% had four plus ACEs, adverse childhood events and 40% screen positive for PTSD. Unfortunately, at baseline for randomization, people in the mindfulness arm had a slightly lower dose, a statistically significant lower dose than control, so we included that in our models. And you can see the past drug use, about 60% of people had previous heroin use. We had a lot of previous opioid use, sedative use, methamphetamine use, and cocaine and crack. Because people already were generally moving towards stability, we only had 6% reporting past-day fentanyl use. So our primary outcome was a mean number of non-abstinent two-week time periods from weeks 13 to 24. What that means is we took the last half of the study, and every two weeks, if they reported, self-reported using opioid use, or they had a positive screen, that was considered a positive, if they had either of those. And what we found, actually, was that there was no difference in opiate abstinence between the two groups. So when you compare these mindfulness groups to a gold-standard control, group-based opiate treatment, we didn't find any difference between those groups. We also didn't find significant differences in cocaine use and benzyl use. It's important to say that all the groups did well, and only about 25% of these two-week time periods across the entire sample were positive for opioids. So that might be one of the things that impacted the study. When we look at anxiety, which is where I really thought we would see a mindfulness pull ahead, what we see is actually that both groups had substantial reductions in anxiety, Cohen's d of 1.2 to 1.3 reductions over the 24 weeks, and no significant difference between the groups. It looks like at week 16, mindfulness was starting to break away, but then by week 24, that changed. Same thing with chronic pain and pain interference. We see pain interference reducing with a moderate effect size in both groups, and no difference between groups. The groups, mindfulness seems like it is doing exactly the same to the gold standard, although this was not a non-inferiority test, so we weren't large enough in power to test that. Where mindfulness really stood out, and I wanna say this is consistent now across all the studies that you've seen, as well as meta-analyses that we've seen for mindfulness and substance use disorder, is in the context of opioid craving. As soon as week two, so we did weekly opioid craving using a scale that Roger's team developed from the POTS trial, and tested in the POTS trial, to look at opiate craving on a weekly basis, and what we found is that as early as week two, we saw mindfulness actually having a statistically significant difference. As we ratcheted up the practice and the training with mindfulness, we actually see that the craving in the mindfulness arm starts to go back up, and then at week 11, there's a rapid decrease in craving that is held for the rest of the study, and just about every week there is significantly different, which is very impactful. What's interesting is that we are increasing people's practice, having them come in contact with their experience, and so their craving is kind of going back up, and then it peaks at week 10 when they start to do the body scan, which is intraceptive awareness, paying attention to body sensations, and they actually can become aware of the body sensations associated with craving. And then after they practice body scan, then we start to see the decrease coming. So I think that that's really an important finding. I'm not gonna get too much into this, but if you wanna look up these papers, if you wanna find out more, what we know is that mindfulness changes the way that we relate to our bodies, that craving is an intraceptive process of comparing the ideal predicted state, how I wanna feel, with how I feel in my body, and it is what largely motivates behavior. And our study on the right, there's a neuroimaging study with this mindful behavior change program that actually showed that people had increased intraceptive attention and increased activation in the insula after mindful behavior change. One of the challenges, this slide is, unfortunately it's not perfect, but I'm just gonna focus on the top line question. So at eight weeks, we asked people if they wanted to continue in the mindfulness arm or not. And what we found was that only 7% of minoritized patients, racial, ethnic, linguistic minorities, actually chose to continue in group. It doesn't mean they didn't keep practicing. They had gotten and been exposed to eight weeks of the program. But only 7% decided to continue, compared to 73% in the control arm that were continuing the gold standard group intervention. So we can talk about this during the discussion, but I think it's an important finding as well. It's important to say that generalizability is limited. These are people that could join live online groups, which we know is not all patients with opiate use disorder. And people had already received 30 days of buprenorphine. We only had a 24-hour testing window. This is oral fluid toxicology in the heart of the pandemic, not perhaps what you might be doing in your clinic with oral toxicology testing. And we found that we had higher retention rates, 72% retention in the R21 pilot when we did it in primary care centers and give out a prescription when people come in to the group. Whereas we only saw, you know, 51% retention at 24 weeks in the study. It's important to say that we only had 9.5% retention during the Delta and Omicron waves, which went up to be much closer to those in-person groups after those waves were done. Let's see, let me just keep going here. So in conclusion, we did not find differences between mindfulness and the gold standard on opiate abstinence, substance use, anxiety, or pain interference over 24 weeks. Both groups had large anxiety reduction over the 24 weeks. And mindfulness, just like other studies that you saw here, reduced opioid craving more than the evidence-based active comparator. And it's important to say that expectations and preference for mindfulness matters. This was a study people did not know they were gonna be offered mindfulness. And so some people may have decided not to continue because they didn't want to engage with mindfulness. It's also possible that, even though we tried to be trauma-informed and engaging, when we had groups where racial, ethnic, and linguistic minorities were often the minority in each group, even if we had culturally concordant group leaders, that they may have experienced as a minoritization. In a way that is harder to tolerate or less likely to want to continue with mindfulness than perhaps in a more general group. It's important to say, on the right here, I just wanna give a shout out to Jeffrey Thomas, who started the Mandela Yoga Project. He's a Robert Wood Johnson fellow at our center now. And what he's been developing is working with peer leaders who are men of color, who also speak Spanish, and are able to, and have experience from the justice system and substance use disorder, who are now out, who he's trained as yoga peer leaders who are training other men who have opiate use disorder when they come out post-incarceration to prevent opiate overdose. And he's doing it in a culturally resonant way, and he's doing it in a place-based, in places that are comfortable for these men of color, and are also doing it with linguistic and cultural adaptations. And I think this, I think this is one of the places that we need to go with mindfulness-based interventions, and find leaders like Jeffrey Thomas to be able to do that work. And it's especially important because, as we know, opiate overdoses have been increasing among people who identify as black, indigenous, and Hispanic. So, thank you very much. I just wanna turn it over now to Roger Weiss, who is a mentor of mine, and is really a generational figure in the field of behavioral interventions for opiate use disorder. Thanks. Thanks, Eric. Thank you. So, one disclosure that wasn't made is, I'm not an expert in mindfulness, unlike everybody else here. But what I do know something about is behavioral treatment of patients with opioid use disorder and with co-occurring disorders, which all of these patients in these three terrific studies had. And I was struck by a couple of things that were said in particular. One is this description Dr. Garland gave. These are diseases of despair. So, when I think of despair, I think another, it's pretty close to hopelessness. And I've done a lot of work with patients with co-occurring substance use disorders and bipolar disorders. And these folks are filled with hopelessness and what I call layers of hopelessness. The first one is I feel hopeless I can stop using alcohol or drugs. And the second one, which I think is the most important one, is I feel hopeless that even if I do stop, that my life will get any better, because I've dug such a deep hole for myself that I'm never gonna get out of it. So, how does that relate to this? How do you get out of a sense of hopelessness? The context of these treatments for opioid use disorder in terms of behavioral treatments is a lot of studies. And I did a review paper a few years ago. Four big studies, including one that I led, showed no benefit of behavioral treatment on top of buprenorphine plus medical management. But when you look at what were these treatments, they were standard drug counseling or cognitive behavioral therapy, and one that had a little bit of contingency management in it. But if you look at CBT and standard drug counseling, they're sort of problem-oriented treatments. Let's look at what the problems are and deal with them. And the word that really hit me was this savoring. Savoring is a positive intervention. And what else has been shown to be helpful with lots of people with substance use disorders is contingency management, which is rewards. And it's all about either external rewards or savoring as an internal reward. And I think that when people are feeling that I've dug this deep hole and I'm never gonna get out of it, they need some sense of success, whether it's externally driven or internally driven that says, that feels better, that feels okay. And that's how they begin to do it. You know, when you're a mile away, you just have to turn in the right direction and each step gets you closer to your goal. But if you feel like you can't even take that first step, what are you gonna do? You're going to continue to just escape. And that's what the drug use often involves. The couple of other points, I think with Dr. Schumann-Olivier's paper, he had such an unbelievably good control group, my goodness, I mean, pretty tough to beat that. And if you look at the characteristics of that control group, it was a lot of positive stuff too. It was not, you know, let's figure out what the problems are it's let's build a sense of community, let's, I don't remember what all the things were, but as I was looking down at, it was all rewarding sorts of behaviors, which I think, you know, with a lot of these treatments, it's not like nobody gets better, but everybody gets better. And so I wouldn't say, gee, this didn't work. It's just, it's an alternative that people can do. And you purposely didn't say that it was mindfulness, but if you add to that, hey, this is a mindfulness group, that's people are going to be into it. So since we only have about three minutes left, just one last thing about craving that you found in your study that craving went down, but not necessarily use. And I think it's important to, you know, craving, it does not necessarily equal use. People who use drugs often use drugs when they don't have a lot of craving because it's a habit or something like that. It's like people who are overweight eat when they're not hungry. So it's not, it's part of the disorder. It's not, I have to wait till my craving level goes up to 10 and then I will use. Craving includes how much you want it and how much you can fight it built into it. And so craving level of eight and fighting it of nine is better than a craving level of one and fighting it of zero. So I'll stop there and take my seat. Thank you. Thank you, Roger, for that great summation. I want to, I guess we can take probably two minutes of questions. I do want to just say that it really took a team and I didn't have a chance to say that before because of time. But this was a center wide and multi-site study. I did want to say that I think that craving is one of the experiences of suffering though. And people, it's a very uncomfortable state. And so in buprenorphine treatment in particular, when there isn't as much use that's happening as people are getting stable, the question is how much are they suffering though with the ongoing temptation and having to hold themselves back. And if they can work with that, well maybe that's where we can start to see people that can be on lower doses of buprenorphine. In fact, we did a buprenorphine reduction study and we found with mindfulness and found that just about everyone could reduce their dose. That's a great point. Why don't we go here and then here. We'll take two questions and then we'll end. Hi there, my name's Kevin Wenzel. I'm a psychologist and research scientist at Maryland Treatment Centers. And I agree with Dr. Garland's statement of the next step is implementation and training of the workforce. I think that's a really cool findings you guys all had and definitely in the next direction. But another direction I was thinking about is adapting the setting. I work in an inpatient like 28 day program and I was wondering if you've thought about how the interventions of mindfulness in all of the studies could be adapted for that type of setting and if you guys are conducting any research. I can comment. So yes, we actually are studying a version of MORE that fits in a 28 day format. We're delivering eight sessions twice a week over four weeks and that enables us to deliver the intervention in that format. The trial's not done yet, but at least logistically, feasibly, it seems to work quite well in that format. Thanks, we're running out of time. So last question. Thank you all so much for this encouraging and hopeful research. I have a question about patients who have difficulty at baseline with regulating their attention, whether they have ADHD or they have depression that impairs their attention. One might think that they might benefit the most from mindfulness training or one might think that they might really struggle the most to engage with mindfulness because they might experience more frustration as they're getting started and I see that when I'm teaching, doing a DBT for substance use disorder group in a residential program. No matter how I couch it, there are always folks who at the end of the intervention say this doesn't work for me and I can't do this and I hate this and I try to help them with it. But so I'm curious in all these different studies, if you're able to tell through analyses or just through your own experience, how those patients tended to do with this and any suggestions for how to best engage folks who find it difficult to regulate their attention at baseline? This is a good question. We did collect some kind of computer adaptive test measure of ADD. We haven't looked at that as a baseline moderator or something like that. What I can tell you is clinically is that a lot of folks that have ADHD often prefer to start with more physical aspects of mindfulness. So mindful movement and different ways to kind of come in to mindfulness because the sitting still can be difficult. But that's also partly why we build up over time and what we find is that if you go right to like 20 minutes a day, a lot of people will have those negative self attributions. I can't do this, this isn't for me. But if we build up slowly, then people can feel that sense of self efficacy and then want to, and as Roger said, kind of feel that sense of hope from whatever the brief experience they have and then can move forward. So yeah, that's my thoughts. And I also think that it's the focus of the intervention and the focus of the mindfulness is to be present with what is and to notice with what is. So it might be that the person becomes aware that they're feeling educated and that they're having judgmental thoughts about what's happening. But that also enables them to have more agency and control over their behaviors because they're noticing what they're experiencing and then be able to make conscious choices in terms of their behavior. So one of the things, like I've done a lot of mindfulness interventions for people in emergency rooms and in hospitals when there's chaos going around all around them and it's just noticing that that is what is right now. And one of the things that we, I just wanted to respond to the other comment about when we were talking about cravings in our pilot study, I didn't mention this, that we actually, awareness of cravings increased in our pilot study, but the ability to resist the urge to act also increased. So even though someone with impulse control difficulties or finding a hard time learning about the awareness of what it's like to be having a hard time and then what do I do when I'm feeling that is also therapeutic and helpful. And I'd just like to add one brief comment, which is a lot of the barriers that people experience in practicing mindfulness relate to misunderstandings about what mindfulness is in the first place. So if the patient believes that they need to have a laser-focused attention with a completely silent mind for 20 minutes straight to be getting benefit out of the intervention, then they're gonna fail. But what we do in mindfulness-oriented recovery enhancement is we use behavioral learning principles to really provide positive reinforcement for even the smallest success, which could be being aware of one breath or two breaths or being aware that the mind is distracted and full of anxious thoughts or pain, but even cultivating that awareness and looking at it without trying to push it away or hold onto it, but just observing your experience like a witness, that is the practice of mindfulness, even if the person's mind is jumping all over the place. Noticing what those thoughts are, that I can't do this, and then to make a choice, but I'm going to do it anyway, as opposed to reflexively just disengaging and not doing it. Thank you. All right, thank you, Dr. Shuman, Oliver, Garland, Cooperman, and Dr. Weiss for that wonderful presentation. And I'm so happy to see another powerful tool in our limited toolbox.

mindfulness-based interventions

opioid use disorder

substance use

craving

pain

mental health

mindfulness interventions

relapse prevention

drug use

training the workforce