My new paper published in the prestigious journal Science Advances reporting effects of Mindfulness-Oriented Recovery Enhancement on brain reward responses among chronic opioid users has been covered by multiple news outlets, including the Los Angeles Times, the Durham Herald-Sun, the Fort Worth Star Telegram, Science Daily, and the American Association for the Advancement of Science, among others. The paper can be downloaded for free here.
Along with my colleagues Drs. Brett Froeliger and Michael Saladin (Medical University of South Carolina), I was recently awarded a 5-year, $2.3 million grant from the National Institute on Drug Abuse to study the neural mechanisms of Mindfulness-Oriented Recovery Enhancement (MORE) as a smoking cessation intervention. In this study, 100 smokers will be randomly assigned to receive eight sessions of MORE or eight sessions of cognitive-behavioral therapy (CBT) to assist them in quitting smoking. Before and after the eight session intervention, participants will complete a task while their brain activity is being recorded in a fMRI scanner to measure their neural response natural rewards and cigarette cues. According to the allostatic model of addiction, as addiction progresses, the brain becomes hypersensitive to drug-related cues and triggers, and insensitive to natural, healthy rewards and pleasures, resulting in a lack of hedonic pleasure and dysphoria that pushes the individual to take higher and higher doses of the drug just to feel okay. This study is designed to test my restructuring reward hypothesis, which states that mindful savoring can reduce addictive behaviors by causing a shift in brain reward circuitry from valuing of drug-related rewards back to valuing natural rewards – reversing the allostatic process of addiction. This new research grant builds upon our earlier published proof-of-concept study showing that MORE increases savoring-related neural activation in the medial prefrontal cortex and ventral striatum – key reward-related brain areas. This increase in brain activity was associated with significant reductions in cigarette smoking. Here we will seek to replicate this finding using a rigorous, randomized clinical trial design. It is my sincere hope that this work will help to free people from smoking – the leading cause of preventable death in the United States.
National Public Radio recently covered a story on Mindfulness-Oriented Recovery Enhancement (MORE) as an intervention for chronic pain and prescription opioid-related problems. The story details new discoveries about the biobehavioral mechanisms of this novel therapy, as well as how mindfulness can be used to improve well-being in individuals suffering from chronic pain.
I‘m pleased to announce that the first fMRI brain imaging study of Mindfulness-Oriented Recovery Enhancement (MORE) has been published in the open-access journal Evidence-Based Complementary and Alternative Medicine (Froeliger et al., 2017). My colleague Brett Froeliger and I conducted this proof-of-concept pilot study at his TRAIN Lab at the Medical University of South Carolina to examine the effects of MORE on reward processes in the brains of people addicted to cigarettes. A sample of 13 smokers participated in a study testing MORE versus a comparison group. All participants underwent two fMRI scans 8 weeks apart. Between the first and second fMRI scan, participants in the MORE group learned mindfulness and reappraisal skills to decrease addictive reactions to cigarettes and savoring skills to increase responsiveness to natural rewards (e.g., social connection, natural beauty, healthy behaviors). Participants in the comparison group completed research measures but did not receive any treatment. Relative to the comparison group, MORE was associated with significant decreases in smoking (66% decrease) and significant increases in positive emotions. Crucially, MORE participants evidenced significant decreases in neural activity while viewing cigarette images in reward-related brain regions including the ventral striatum and ventral prefrontal cortex. MORE participants also demonstrated significant increases in neural activity in these same reward-related brain regions while they savored positive, natural-reward related images. Importantly, increases in brain activity during savoring were significantly correlated with smoking reduction and increased positive affect. Though this study had a number of limitations, including the small sample size and lack of a randomized design, these pilot findings provide preliminary evidence that MORE may facilitate the restructuring of reward processes and play a role in treating the pathophysiology of nicotine addiction. These findings converge with results from our other psychophysiological studies indicating that MORE may restructure reward processes in prescription opioid misuse (Garland, Froeliger, & Howard, 2014; Garland, Froeliger, & Howard, 2015; Garland, Howard, Zubieta, & Froeliger, 2017). Taken together, these data provide initial support for my restructuring reward hypothesis which asserts that mindfulness training may enhance a domain-general cognitive resource for restructuring reward learning from valuation of drug-related rewards to valuation of natural rewards and thereby reverse the downward spiral of addiction.
Recently, I was awarded a R01 grant from the National Institute on Drug Abuse to conduct a full-scale clinical trial of Mindfulness-Oriented Recovery Enhancement (MORE) as an intervention to reduce chronic pain and prescription opioid misuse in primary care. This five-year study will compare the efficacy of MORE to supportive therapy for 260 chronic pain patients receiving long-term opioid therapy who are at risk for opioid misuse.
Opioids may be medically necessary for some individuals experiencing prolonged and intractable pain, and most patients take medicine as prescribed. Unfortunately, opioids rarely completely alleviate chronic pain, and when taken in high doses or for long periods of time, can lead to serious side effects, including death by overdose, as well as risk for opioid misuse, which affects about 1 in 4 opioid-treated patients. Misusing opioids by taking higher doses than prescribed or by taking opioids to self-medicate negative emotions can alter the brain’s capacity for hedonic regulation, making it difficult to cope with pain (e.g., causing hyperalgesia – an increased sensitivity of the nervous system to pain) and experience pleasure in life (e.g., reducing sensitivity of the brain to natural reward). As such, non-opioid pain treatments that target hedonic dysregulation may be especially helpful for reducing chronic pain and prevent opioid misuse.
Multiple studies suggest that MORE improves hedonic regulation in the brain, resulting in decreased pain and an increased ability to savor natural, healthy pleasure. People who participate in MORE show heightened brain and body responses to healthy pleasures, and report feeling more positive emotions by using of mindfulness as a tool to enhance savoring. These therapeutic effects of MORE on savoring may be critically important, because findings from several studies show that increasing sensitivity to natural reward through savoring may lead to decreased craving for drugs – a completely novel finding for the field of addiction science (Garland, 2016). Our NIDA-funded R01 will provide a rigorous test of whether MORE improves chronic pain and opioid misuse by targeting hedonic dysregulation.
In our NIDA-funded R01, patients are receiving MORE at community medical clinics throughout Salt Lake City. Providing MORE in the naturalistic setting where most chronic pain patients seek medical care will make the therapy accessible to the people who need it the most. Ultimately, my hope is that this project will advance a new form of integrative healthcare, in which doctors and nurses work alongside social workers and other behavioral health professionals to help patients reclaim a meaningful life from pain.
Chronic pain is often treated with extended use of opioid analgesics, yet these drugs can alter the brain in ways that may make it difficult to cope with pain and may reduce the experience pleasure in life. Mindfulness-based interventions appear to be a promising means of addressing these issues, but research is needed to understand how such interventions change the brain to reduce suffering.
To that end, in September, 2016, I was recently awarded a five-year phased innovation grant from the National Institutes of Health’s (NIH) National Center for Complementary and Integrative Health entitled Effects of Mindfulness-Oriented Intervention on Endogenous Opioid Mechanisms of Hedonic Regulation in Chronic Pain (R61AT009296). The objective of the project is to study the effects of an innovative mindfulness-based intervention on brain mechanisms linked with pain and pleasure.
In the first two-year phase of the study ($800,000), I (Principal Investigator), along with my Co-Principal Investigator Jon-Kar Zubieta (Co-Principal Investigator), chair of the University of Utah’s Department of Psychiatry, will use positron emission tomography (PET) neuroimaging to assess the effects of Mindfulness-Oriented Recovery Enhancement (MORE) on restoring brain levels of endorphins in patients with chronic back pain who are being treated with prescription opioids.
This study represents the first use of PET in the history of science to quantify the effects of a mindfulness-based therapy on levels of endogenous opioids in the brain.
We will also use functional magnetic resonance imaging (fMRI) methods to assess how mindfulness training through MORE may increase people’s capacity to savor natural pleasure from positive and meaningful events in everyday life – a capacity that becomes diminished over time through the deleterious effects of chronic pain and prolonged opioid use on the brain. We will use a fMRI paradigm developed by my Co-Investigator Brett Froeliger, Assistant Professor of Neuroscience at the Medical University of South Carolina.
This study aims to test whether MORE might reverse this insensitivity to natural reward by targeting the endogenous opioid system and brain reward functions.
Following a successful first phase of the project, a three-year second phase ($2.2 million) will investigate whether patients with a particular genetic makeup that affects the expression of opioid receptors in the brain might benefit more from the mindfulness-based treatment. The second phase of the project will also assess the dose of mindfulness skill practice as a predictor of changes in endogenous opioid function and clinical correlates.
Based on the results of previous research, we hypothesize that mindfulness meditation training through MORE will restore proper function to the brain’s opioid receptors. We will be able to measure how MORE changes the brain’s ability to regulate pain and respond to natural rewards, as well as deepen our understanding of exactly how these changes in neural mechanisms happen.
Overall, this project will unite expertise in mindfulness-based interventions with expertise in neurogenetics and the use of PET and fMRI to probe the neurobiological mechanisms of pain and emotional experience. By elucidating a key mechanism of meditation-based therapies, this program of translational research will further the emerging field of social work neuroscience and enable us to rapidly optimize MORE to increase the effectiveness of the intervention as it is rolled out in clinical practice.
I recently learned that my research on Mindfulness-Oriented Recovery Enhancement (MORE) was highlighted on the National Institute on Drug Abuse website. The NIDA news story, entitled “Mindfulness training may reduce deficits in natural reward processing during chronic pain or drug addiction” details a study I conducted with my colleagues Brett Froeliger (Neuroscience, Medical University of South Carolina) and Matthew Howard (Social Work, University of North Carolina at Chapel Hill) that was published in April in the Journal of Behavioral Medicine. According to the excellent summary of this research on the NIDA website,
“Drug-dependent people show decreased behavioral and brain reactivity to natural rewards compared to non-drug users. As a result, drug-dependent users increasingly focus their attention on obtaining the drug instead of attending to natural rewards. Recent research shows that a cognitive-based intervention may help restore natural reward processing in opioid-dependent participants.
In this study, chronic pain patients at risk for opioid misuse were randomized to either eight weeks of a Mindfulness-Oriented Recovery Enhancement (MORE) intervention or to an eight-week support group (control). Participants in the MORE intervention used mindfulness meditation to focus on all sensory features of a pleasant experience or object (for example, a beautiful nature scene like a sunset), while reflecting on any positive emotions arising in response to the pleasant event. The support group discussed topics and emotions related to chronic pain and opioid use/misuse. Following these interventions, all participants were shown images representing natural rewards (such as endearing animals, appealing foods, landscapes) or neutral images (furniture, neutral facial expressions, or household items). Researchers measured late positive potential (LPP) brain activity, which reflects attention to emotionally salient information, while participants viewed these images. In comparison to the control group, participants completing the MORE intervention showed greater LPP responses to natural reward images relative to neutral images and greater the LPP responses predicted reduced opioid cravings as reported by the participants.”
These results suggest that teaching people who misuse opioids to mindfully attend to positive aspects of their life may increase the perceived value of natural rewards – processes that may be diminished in those facing chronic pain or addiction – which may in turn help them to control opioid cravings.”
It is thrilling to see that this line of research is making a positive impact on the scientific community, and of course, the ultimate aim of this work is to alleviate human suffering.