At the intersection of sleep deficiency and opioid use: mechanisms and therapeutic opportunities

Due to the ongoing opioid epidemic, innovative scientific perspectives and approaches are urgently needed to reduce the unprecedented personal and societal burdens of nonmedical and recreational opioid use. One promising opportunity is to focus on the relationship between sleep deficiency and opioid use. In this review, we examine empirical evidence: (1) at the interface of sleep deficiency and opioid use, including hypothesized bidirectional associations between sleep efficiency and opioid abstinence; (2) as to whether normalization of sleep deficiency might directly or indirectly improve opioid abstinence (and vice versa); and (3) regarding mechanisms that could link improvements in sleep to opioid abstinence. Based on available data, we identify candidate sleep-restorative therapeutic approaches that should be examined in rigorous clinical trials

Anhedonia modulates benzodiazepine and opioid demand among persons in treatment for opioid use disorder

BACKGROUND: Benzodiazepine (BZD) misuse is a significant public health problem, particularly in conjunction with opioid use, due to increased risks of overdose and death. One putative mechanism underlying BZD misuse is affective dysregulation, via exaggerated negative affect (e.g., anxiety, depression, stress-reactivity) and/or impaired positive affect (anhedonia). Similar to other misused substances, BZD consumption is sensitive to price and individual differences. Although purchase tasks and demand curve analysis can shed light on determinants of substance use, few studies have examined BZD demand, nor factors related to demand. METHODS: This ongoing study is examining simulated economic demand for alprazolam (among BZD lifetime misusers based on self-report and DSM-5 diagnosis; n = 23 total; 14 male, 9 female) and each participant\u27s preferred-opioid/route using hypothetical purchase tasks among patients with opioid use disorder (n = 59 total; 38 male, 21 female) who are not clinically stable, i.e., defined as being early in treatment or in treatment longer but with recent substance use. Aims are to determine whether: (1) BZD misusers differ from never-misusers on preferred-opioid economic demand, affective dysregulation (using questionnaire and performance measures), insomnia/behavioral alertness, psychiatric diagnoses or medications, or urinalysis results; and (2) alprazolam demand among BZD misusers is related to affective dysregulation or other measures. RESULTS: Lifetime BZD misuse is significantly (p \u3c 0.05) related to current major depressive disorder diagnosis, opioid-negative and methadone-negative urinalysis, higher trait anxiety, greater self-reported affective dysregulation, and younger age, but not preferred-opioid demand or insomnia/behavioral alertness. Alprazolam and opioid demand are each significantly positively related to higher anhedonia and, to a lesser extent, depression symptoms but no other measures of negative-affective dysregulation, psychiatric conditions or medications (including opioid agonist therapy or inpatient/outpatient treatment modality), or sleep-related problems. CONCLUSION: Anhedonia (positive-affective deficit) robustly predicted increased BZD and opioid demand; these factors could modulate treatment response. Routine assessment and effective treatment of anhedonia in populations with concurrent opioid and sedative use disorder may improve treatment outcomes

A virtual reality martial arts-based intervention reduces pain, drug craving, and stress in patients with opioid use disorder

Background: Some individuals with opioid use disorder (OUD) report high levels of pain, anxiety, stress and drug craving that may occasion relapse, reduce adherence to treatment, and reduce quality of life. This pilot study evaluated whether a novel martial arts-based intervention can lower self-reported and physiological markers of pain, anxiety, stress and opioid craving in individuals with OUD undergoing methadone maintenance treatment (MMT). Methods: 15 MMT patients (11 females) completed a 12-week ‘Heroes Circle’ intervention that involved twice-weekly 30-min sessions centering around martial arts-based breathing and meditative techniques using therapist-assisted virtual reality (VR). Patients self-reported on five measures (pain, drug craving, anxiety, depression, anger) using a 0-10 scale before (pre) and after (post) each session. Salivary markers of inflammation (C-reactive protein [CRP]) and stress (cortisol) were collected before and after several sessions (baseline, weeks 4, 8, and 12). Results: There were significant pre-post session reductions in rated pain, drug craving, anxiety and depression, and saliva cortisol (ps\u3c0.05). For opioid craving, there was also an effect of week such that craving decreased from weeks 1-6, increased from 7-9, and decreased again from 10-12 (ps\u3c0.05); there was also a session x week interaction such that the pre-post reduction in craving reached significance in weeks 1-3 only. There were no significant main effects or interactions for anger or CRP (ps\u3e0.05). Conclusions: These preliminary results suggest VR-based, martial-arts meditative intervention is a promising approach for reducing pain, anxiety, stress and craving levels among individuals with OUD. Further controlled studies are warranted

A novel martial arts-based virtuality reality intervention modulates pain and the pain neuromatrix in patients with opioid use disorder

Background: Standard-of-care for opioid use disorder (OUD) includes medication and counseling. However, there is an unmet need for complementary approaches to treat OUD patients coping with pain; furthermore, few studies have probed neurobiological features of pain or its management during OUD treatment. This preliminary study examines neurobiological and behavioral effects of a martial arts-based intervention in patients undergoing methadone maintenance treatment (MMT). Methods: Fifteen (11 female) MMT patients completed a virtual reality, therapist-guided martial arts intervention that included breathing and relaxation exercises; sessions were scheduled twice weekly. Assessments included functional magnetic resonance imaging (fMRI) of pain neuromatrix activation and connectivity (pre- and post-intervention), saliva cortisol and C-reactive protein (CRP) at baseline and weeks 4, 8 and 12; and self-reported pain and affective symptoms before and after each intervention session. Results: After each intervention session (relative to pre-session), ratings of pain, opioid craving, anxiety and depression (but not anger) decreased. Saliva cortisol (but not CRP) levels decreased from pre- to post-session. From pre- to post-intervention fMRI assessments, pain task-related left postcentral gyrus (PCG) activation decreased. Higher baseline cortisol levels were associated with greater post-intervention pain task-related insular activation. At baseline, PCG showed positive connectivity with other regions of the pain neuromatrix, but this pattern changed post-intervention. Conclusions: These preliminary findings demonstrate feasibility, therapeutic promise, and brain basis of a martial arts-based intervention for OUD patients undergoing MMT

Effects of Cocaine and/or Heroin Use on Resting Cardiovascular Function

Background: Regular cocaine and/or heroin use is associated with major health risks, especially cardiovascular disease (CVD), but confounded by other factors. Objectives: We examined effects of chronic (years of regular use) and recent (past-month) use of cocaine and heroin, controlling for other factors, on resting cardiovascular function. Methods: In a sample of cocaine and/or heroin users (N=292), we obtained data on demographics, body mass index (BMI), history of substance use, and electrocardiogram, heart rate (HR) and blood pressure (BP). Following bivariate correlations, three-block (1: demographics, BMI; 2: tobacco, alcohol, marijuana; 3: cocaine, heroin) regression analyses were conducted to predict cardiovascular measures. Results: Higher BMI predicted increased systolic and diastolic BP (as did older age), increased supine HR, and longer QRS duration, QTc interval, PR interval, and P-wave duration. Recent substance use had more reliable effects than chronic use on cardiovascular measures. Past-month marijuana-use days predicted higher systolic BP, lower supine HR, and greater likelihood of early repolarization and ST elevation, whereas average daily marijuana use predicted shorter QTc interval. Average daily alcohol use predicted higher diastolic BP, higher supine HR and lower likelihood of sinus bradycardia (HRbpm). Past-month tobacco-use days predicted shorter QTc interval and increased likelihood of profound bradycardia (HRbpm). Past-month heroin-use days predicted lower seated HR, greater likelihood of sinus bradycardia and lower likelihood of left ventricular hypertrophy. More years of regular cocaine use and past-month cocaine-use days predicted longer QTc interval. Conclusions: Cocaine and heroin incrementally predicted modest variance in resting bradycardia and QTc interval. Clinicians should first consider demographics and recent use of tobacco, alcohol and marijuana before assuming cocaine and heroin affect these measures

A sense of embodiment is reflected in people's signature size

BACKGROUND: The size of a person's signature may reveal implicit information about how the self is perceived although this has not been closely examined. METHODS/RESULTS: We conducted three experiments to test whether increases in signature size can be induced. Specifically, the aim of these experiments was to test whether changes in signature size reflect a person's current implicit sense of embodiment. Experiment 1 showed that an implicit affect task (positive subliminal evaluative conditioning) led to increases in signature size relative to an affectively neutral task, showing that implicit affective cues alter signature size. Experiments 2 and 3 demonstrated increases in signature size following experiential self-focus on sensory and affective stimuli relative to both conceptual self-focus and external (non-self-focus) in both healthy participants and patients with anorexia nervosa, a disorder associated with self-evaluation and a sense of disembodiment. In all three experiments, increases in signature size were unrelated to changes in self-reported mood and larger than manipulation unrelated variations. CONCLUSIONS: Together, these findings suggest that a person's sense of embodiment is reflected in their signature size

Production of a long-term global water vapor and liquid water data set using ultra-fast methods to assimilate multi-satellite and radiosonde observations

There is a well-documented requirement for a comprehensive and accurate global moisture data set to assist many important studies in atmospheric science. Currently, atmospheric water vapor measurements are made from a variety of sources including radiosondes, aircraft and surface observations, and in recent years, by various satellite instruments. Creating a global data set from a single measuring system produces results that are useful and accurate only in specific situations and/or areas. Therefore, an accurate global moisture data set has been derived from a combination of these measurement systems. Under a NASA peer-reviewed contract, STC-METSAT produced two 5-yr (1988-1992) global data sets. One is the total column (integrated) water vapor data set and the other, a global layered water vapor data set using a combination of radiosonde observations, Television and Infrared Observation Satellite (TIROS) Operational Satellite (TOVS), and Special Sensor Microwave/Imager (SSM/I) data sets. STC-METSAT also produced a companion, global, integrated liquid water data set. The complete data set (all three products) has been named NVAP, an anachronym for NASA Water Vapor Project. STC-METSAT developed methods to process the data at a daily time scale and 1 x 1 deg spatial resolution

Production of long-term global water vapor and liquid water data set using ultra-fast methods to assimilate multi-satellite and radiosonde observations

In recent years climate research scientists have recognized the need for increased time and space resolution precipitable and liquid water data sets. This project is designed to meet those needs. Specifically, NASA is funding STC-METSAT to develop a total integrated column and layered precipitable water data set. This is complemented by a total column liquid water data set. These data are global in extent, 1 deg x 1 deg in resolution, with daily grids produced. Precipitable water is measured by a combination of in situ radiosonde observations and satellite derived infrared and microwave retrievals from four satellites. This project combines these data into a coherent merged product for use in global climate research. This report is the Year 2 Annual Report from this NASA-sponsored project and includes progress-to-date on the assigned tasks

Production of long-term global water vapor and liquid water data set using ultra-fast methods to assimilate multi-satellite and radiosonde observations

During the next decade, many programs and experiments under the Global Energy and Water Cycle Experiment (GEWEX) will utilize present day and future data sets to improve our understanding of the role of moisture in climate, and its interaction with other variables such as clouds and radiation. An important element of GEWEX will be the GEWEX Water Vapor Project (GVaP), which will eventually initiate a routine, real-time assimilation of the highest quality, global water vapor data sets including information gained from future data collection systems, both ground and space based. The comprehensive global water vapor data set being produced by METSAT Inc. uses a combination of ground-based radiosonde data, and infrared and microwave satellite retrievals. This data is needed to provide the desired foundation from which future GEWEX-related research, such as GVaP, can build. The first year of this project was designed to use a combination of the best available atmospheric moisture data including: radiosonde (balloon/acft/rocket), HIRS/MSU (TOVS) retrievals, and SSM/I retrievals, to produce a one-year, global, high resolution data set of integrated column water vapor (precipitable water) with a horizontal resolution of 1 degree, and a temporal resolution of one day. The time period of this pilot product was to be det3ermined by the availability of all the input data sets. January 1988 through December 1988 were selected. In addition, a sample of vertically integrated liquid water content (LWC) was to be produced with the same temporal and spatial parameters. This sample was to be produced over ocean areas only. Three main steps are followed to produce a merged water vapor and liquid water product. Input data from Radiosondes, TOVS, and SSMI/I is quality checked in steps one and two. Processing is done in step two to generate individual total column water vapor and liquid water data sets. The third step, and final processing task, involves merging the individual output products to produce the integrated water vapor product. A final quality control is applied to the merged data sets