New Research Funding: Understanding the Neural Mechanisms of MORE as a Treatment for Smoking Cessation

Along with my colleagues Drs. Brett Froeliger and nidaMichael 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 MORE-fMRI-SBmedial 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.

Research on MORE and Mindfulness Covered in the News

Results from a new Stage 2 randomized controlled trial of Mindfulness-Oriented Recovery Enhancement (MORE), to be published later this summer in the Journal of Consulting and Clinical Psychology, have been covered in a news story that also details findings from a recently published study of the effects of mindfulness on deautomatization of habit behaviors. A second news story also did a really nice job describing results from this study.

Results from this study, conducted in 95 people with chronic pain who had been prescribed long-term opioid therapy, demonstrate that MORE significantly decreased chronic pain intensity and significantly decreased the risk of future opioid misuse. Further, MORE boosted a range of positive psychological functions, including positive emotions, savoring, meaning in life, and the sense of self-transcendence. Importantly, the MORE’s effects on reducing pain and opioid misuse were linked with these increases in positive psychological functioning, suggesting that teaching people to “savor the good” and increase the sense of joy, meaningfulness, and natural healthy pleasure in life may be an antidote to the current pain and opioid crises in America – modern epidemics that have been termed “diseases of despair.”

This is the second randomized controlled trial to demonstrate therapeutic effects of MORE on chronic pain symptoms and opioid misuse, providing compelling evidence of MORE’s efficacy as a means of alleviating the suffering caused by the opioid crisis.

Mindfulness-Oriented Recovery Enhancement Covered on NPR

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.

The NPR story can be found here.

 

 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

more-conceptual-framework-opioid

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

 

 

News: Dr. Garland’s Biobehavioral Research on MORE and Mindful Savoring Highlighted by the National Institute on Drug Abuse

MORE Reward ERPI 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 tetonsRecovery 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.

Chronic Pain Treatment, Neuroscience, and Genetics – Mindfulness-Oriented Recovery Enhancement on the Radio

Today I had the opportunity to speak about the treatment, neuroscience, and genetics of chronic pain with Dr. Dan Gottlieb, host of Voices in the Family, and Dr. Jeffrey Mogil, head of the Pain Genetics Lab at McGill University, on radio station WHYY in Philadelphia (a local NPR station). I spoke about how negative emotions and stress can influence pain processing in the brain, and about how Mindfulness-Oriented Recovery Enhancement can reduce the harmful impact of negative emotions on pain by teaching people to change the way they focus their attention and to reinterpret chronic pain as innocuous sensory signals from the body. 

The entire interview can be found here:

New Paper Accepted for Publication: Mindfulness Training Targets Neurocognitive Mechanisms of Addiction at the Attention-Appraisal-Emotion Interface

mindfulness centered regulation
Neurocognitive Model of Mindfulness-Centereted Regulation (Garland, Froeliger, & Howard, 2014)

My colleagues Brett Froeliger, Matthew Howard, and I recently authored an invited conceptual review paper (FREE TO DOWNLOAD) for a special issue of Frontiers in Psychiatry: Addictive Disorders and Behavioral Dyscontrol. Prominent neuroscience models suggest that addictive behavior occurs when environmental stressors and drug-relevant cues activate a cycle of cognitive, affective, and psychophysiological mechanisms, including dysregulated interactions between bottom-up and top-down neural processes, that compel the user to seek out and use drugs. Mindfulness-based interventions (MBIs) target pathogenic mechanisms of the risk chain linking stress and addiction. This review describes how MBIs may target neurocognitive mechanisms of addiction at the attention-appraisal-emotion interface. Empirical evidence is presented suggesting that MBIs ameliorate addiction by enhancing cognitive regulation of a number of key processes, including: clarifying cognitive appraisal and modulating negative emotions to reduce perseverative cognition and emotional arousal; enhancing metacognitive awareness to regulate drug-use action schema and decrease addiction attentional bias; promoting extinction learning to uncouple drug-use triggers from conditioned appetitive responses; reducing cue-reactivity and increasing cognitive control over craving; attenuating physiological stress reactivity through parasympathetic activation; and increasing savoring to restore natural reward processing. Treatment and research implications of our neurocognitive framework are presented. We conclude by offering a temporally sequenced description of neurocognitive processes targeted by MBIs through a hypothetical case study. Our neurocognitive framework has implications for the optimization of addiction treatment with MBIs.

The conceptual framework outlined in this paper clarifies and contextualizes the recent results from our randomized controlled trial of Mindfulness-Oriented Recovery Enhancement as a treatment for prescription opioid misuse and chronic pain.

New Paper Accepted for Publication: Mindfulness-Oriented Recovery Enhancement for Chronic Pain and Prescription Opioid Misuse – Results from an Early Stage Randomized Controlled Trial

Results from my NIH-funded clinical trial of Mindfulness-Oriented Recovery Enhancement (MORE) as a treatment for chronic pain and prescription opioid misuse were recently accepted for publication in the prestigious, top-tier Journal of Consulting and Clinical Psychology. Study findings demonstrated that MORE significantly reduced chronic pain, pain-related impairment, and stress while decreasing craving and opioid misuse among a sample of 115 people who had taken prescription opioid painkillers for more than three months. The effects of MORE on reducing pain severity and pain-related impairment were maintained for 3 months after the end of treatment, and MORE reduced disordered opioid use by 63%. These positive outcomes were linked with the development of mindfulness skills that are specifically strengthened by MORE, like the ability to “step back” and objectively observe negative thoughts and feelings in a non-reactive manner,  the ability to reinterpret pain sensations as harmless sensory information, and the ability to reappraise adverse life events as opportunities for personal growth and meaning.  In addition, participation in MORE weakened the link between desire for opioids and opioid misuse, suggesting that people who learned to use mindfulness to deal with craving were less likely to take inappropriate doses of opioids or to use opioids to self-medicate stress and negative emotions.

In some circumstances, opioids may be medically necessary for individuals experiencing prolonged and intractable pain, and most patients take medicine as prescribed. Nonetheless, opioids rarely completely alleviate chronic pain, and may lead to serious side effects, including death by overdose, as well as risk for developing opioid-related problems and addiction. As such, new interventions are needed to target chronic pain and prevent opioid misuse. Study findings indicate that MORE is a promising treatment for this growing problem. Over the next few years, additional social, psychological, and neuroscientific studies will reveal the many pathways by which MORE produces its therapeutic effects.