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Sleep problems are commonly reported during opioid agonist treatment (OAT) for opioid use disorders. Inpatient studies have found both sleep disturbances and improved sleep during OAT. Illicit opioids can also disrupt sleep, but it is unclear how they affect sleep in outpatients receiving OAT. Therefore, we used electronic diary entries and actigraphy to measure sleep duration and timing in opioid-dependent participants (n = 37) treated with methadone (n = 15) or buprenorphine (n = 22). For 16 weeks, participants were assigned to attend our clinic under different operating hours in a crossover design: Early hours (07:00–09:00) vs. Late hours (12:00–13:00) for 4 weeks each in randomized order, followed for all participants by our Standard clinic hours (07:00–11:30) for 8 weeks. Throughout, participants made daily electronic diary self-reports of their sleep upon waking; they also wore a wrist actigraph for 6 nights in each of the three clinic-hour conditions. Drug use was assessed by thrice-weekly urinalysis. In linear mixed models controlling for other sleep-relevant factors, sleep duration and timing differed by drug use and by clinic hours. Compared to when non-using, participants slept less, went to bed later, and woke later when using illicit opioids and/or both illicit opioids and cocaine. Participants slept less and woke earlier when assigned to the Early hours. These findings highlight the role OAT clinic schedules can play in structuring the sleep/wake cycles of OAT patients and clarify some of the circumstances under which OAT patients experience sleep disruption in daily life.

In addiction, risk factors for craving and use include stress and drug-related cues. Stress and cues have additive or more-than-additive effects on drug seeking in laboratory animals, but, surprisingly, seem to compete with one another (ie, exert less-than-additive effects) in human laboratory studies of craving. We sought heretofore elusive evidence that human drug users could show additive (or more-than-additive) effects of stress and cues on craving, using ecological momentary assessment (EMA). Outpatients (N=182) maintained on daily buprenorphine or methadone provided self-reports of stress, craving, mood, and behavior on electronic diaries for up to 16 weeks. In three randomly prompted entries (RPs) per day, participants reported the severity of stress and craving and whether they had seen or been offered opioids, cocaine, cannabis, methamphetamine, alcohol, or tobacco. In random-effects models controlling for between-person differences, we tested effects of momentary drug-cue exposure and stress (and their interaction) on momentary ratings of cocaine and heroin craving. For cocaine craving, the Stress × Cue interaction term had a positive mean effect across participants (M=0.019; CL95 0.001-0.036), denoting a more-than-additive effect. For heroin, the mean was not significantly greater than 0, but the confidence interval was predominantly positive (M=0.019; CL95 -0.007-0.044), suggesting at least an additive effect. Heterogeneity was substantial; qualitatively, the Stress × Cue effect appeared additive for most participants, more than additive for a sizeable minority, and competitive in very few. In the field, unlike in human laboratory studies to date, craving for cocaine and heroin is greater with the combination of drug cues and stress than with either alone. For a substantial minority of users, the combined effect may be more than additive.

Background and aims Stress can be validly assessed “live” or by a summary evaluation of the very recent past. Using smartphone-based ecological momentary assessment (EMA) combined with end-of-day (EOD) entries, we assessed the association between daily hassles, stressful events and use of opioids and cocaine, in opioid- and cocaine-using men and women. Methods For up to 16 weeks, 161 outpatients in opioid-agonist treatment who reported cigarette smoking carried smartphones on which they reported stressful events (SEs) and drug use (DU) and completed an EOD questionnaire to report hassles encountered throughout the day, current perceived stress, cigarettes/day, and current mood. We compared EOD responses on days with and without SE and DU reports and on days when thrice-weekly urine drug screens indicated opioid or cocaine use or abstinence. Results Participants (N = 161) made 11,544 EOD entries; EMA SEs were reported on 861 (7.5%) days, and DUs on 1685 (14.6%) days. The most frequently reported hassles in EOD entries were “not enough money” (31.4% of daily reports) and maintaining abstinence (18.7%). Total EOD hassles showed small but statistically significant associations [odds ratios (95% CIs)] with EMA SEs [1.09 (1.06–1.13)], DUs [1.08 (1.06–1.10)], and urine-positive opioid [1.06 (1.04–1.09)] and cocaine [1.03 (1.00–1.06)] results. Men and women had similar rates (mean/day (SD)) of hassles: men 2.25 (3.55); women 2.55 (3.76) (F1,159 = 0.53, p = 0.47). Conclusions Daily hassles, reported at the end of the day, are associated with both same-day stressful events and drug use. Monitoring hassles and devising specific coping strategies might be useful therapeutic targets.

We investigated relationships between drinking, other drug use, and drug craving, using ecological momentary assessment (EMA), in a sample of polydrug users who were not heavy drinkers. In a prospective longitudinal cohort study, 114 heroin and cocaine users on methadone-maintenance treatment carried handheld electronic diaries during waking hours and were screened for drug and alcohol use for up to 25 weeks. Individuals who fulfilled the Diagnostic and Statistical Manual of Mental Disorders criteria for alcohol abuse or dependence were excluded. Participants responded to 2-5 random prompts per day to report on their moods, cravings, and activities and initiated entries when they used or acutely craved heroin or cocaine. Drinking alcohol was assessed in both types of entries. Breath alcohol was measured three times weekly. Participants reported drinking alcohol in 1.6% of random-prompt entries, 3.7% of event-contingent entries when craving cocaine and/or heroin, and 11.6% of event-contingent entries when using cocaine and/or heroin. Alcohol drinking was also associated with higher craving ratings and prestudy alcohol use. More drinking was detected by ambulatory self-report than by in-clinic breath testing. Even though we had screened out heavy drinkers from our sample of polydrug users, drinking was associated with heroin and cocaine craving and actual use. Language: en

Stress’s role in drug use is supported by retrospective interview and laboratory studies, but prospective data confirming the association in daily life are sparse. This study aims to assess the relationship between drug use and stress in real time with ambulatory monitoring. For up to 16 weeks, 133 outpatients on opiate agonist treatment used smartphones to report each time they used drugs or felt more stressed than usual. They rated stress-event severity on a 10-point scale and as a hassle, day spoiler, or more than a day spoiler. For analysis, stress reports made within 72 h before a reported use of cocaine or opioid were binned into 24-h periods. Of 52 participants who reported stress events in the 72-h timeframe, 41 reported stress before cocaine use and 26 before opioid use. For cocaine use, the severity of stressors, rated numerically (r effect = 0.42, CL95 0.17–0.62, p = 0.00061) and percent rated as “more than a day spoiler” (r effect = 0.34, CL95 0.07–0.56, p = 0.0292)], increased linearly across the three days preceding use. The number of stressors did not predict cocaine use, and no measure of stress predicted opioid use. In ecological momentary assessment (EMA) from the whole sample of 133, stress and drug use occurred independently and there was no overall relationship. EMA did not support the idea that stress is a necessary or sufficient trigger for cocaine or heroin use after accounting for the base rates of stress and use. But EMA did show that stressful events can increase in severity in the days preceding cocaine use.

Ambulatory physiological monitoring could clarify antecedents and consequences of drug use and could contribute to a sensor-triggered mobile intervention that automatically detects behaviorally risky situations. Our goal was to show that such monitoring is feasible and can produce meaningful data.We assessed heart rate (HR) with AutoSense, a suite of biosensors that wirelessly transmits data to a smartphone, for up to 4 weeks in 40 polydrug users in opioid-agonist maintenance as they went about their daily lives. Participants also self-reported drug use, mood, and activities on electronic diaries. We compared HR with self-report using multilevel modeling (SAS Proc Mixed).Compliance with AutoSense was good; the data yield from the wireless electrocardiographs was 85.7%. HR was higher when participants reported cocaine use than when they reported heroin use (F(2,9)=250.3, p.0001) and was also higher as a function of the dose of cocaine reported (F(1,8)=207.7, p.0001). HR was higher when participants reported craving heroin (F(1,16)=230.9, p.0001) or cocaine (F(1,14)=157.2, p.0001) than when they reported of not craving. HR was lower (p.05) in randomly prompted entries in which participants reported feeling relaxed, feeling happy, or watching TV, and was higher when they reported feeling stressed, being hassled, or walking.High-yield, high-quality heart-rate data can be obtained from drug users in their natural environment as they go about their daily lives, and the resultant data robustly reflect episodes of cocaine and heroin use and other mental and behavioral events of interest.

Stress can lead to headaches and fatigue, precipitate addictive behaviors (e.g., smoking, alcohol and drug use), and lead to cardiovascular diseases and cancer. Continuous assessment of stress from sensors can be used for timely delivery of a variety of interventions to reduce or avoid stress. We investigate the feasibility of continuous stress measurement via two field studies using wireless physiological sensors --- a four-week study with illicit drug users (n = 40), and a one-week study with daily smokers and social drinkers (n = 30). We find that 11+ hours/day of usable data can be obtained in a 4-week study. Significant learning effect is observed after the first week and data yield is seen to be increasing over time even in the fourth week. We propose a framework to analyze sensor data yield and find that losses in wireless channel is negligible; the main hurdle in further improving data yield is the attachment constraint. We show the feasibility of measuring stress minutes preceding events of interest and observe the sensor-derived stress to be rising prior to self-reported stress and smoking events.

PAK5 and PAK6 are protein kinases highly expressed in the brain. Previously, we observed that Pak6 knockout mice gained significantly more weight during development than Pak5 knockout mice as well as wild-type controls and double-knockout mice lacking both Pak5 and Pak6. In this study, we assessed the effects of exercise on food intake and weight gain of these mice as well as their sensitivity to the stimulant effects of amphetamine.Mice of each genotype were placed in cages with free access to run wheel exercise or in cages without run wheels for a total of 74 days. Food and fluid intake as well as body weight of each mouse were measured on a weekly basis. Finally, mice were given a high dose of amphetamine and activity levels were observed immediately thereafter for 90 minutes. Brains and testes of mice were assayed for protein levels of the estrogen alpha and progesterone receptors.While run wheel mice consumed significantly more food, they weighed less than non-run wheel mice. In addition, although Pak6 knockout mice consumed the same amount of food as wild-type mice, they were significantly heavier regardless of run wheel condition. Pak5 knockout mice were found to be more active than other genotypes after amphetamine treatment. Finally, protein levels of the progesterone and estrogen alpha receptors were altered in brain and testes of the Pak6 knockout mice.Collectively, these data suggest that PAK6 play a role in weight gain unrelated to exercise and caloric intake and that Pak5 knockout mice are more sensitive to the stimulant effects of amphetamine.

Maladaptive behaviors may be more fully understood and efficiently prevented by ambulatory tools that assess people's ongoing experience in the context of their environment.To demonstrate new field-deployable methods for assessing mood and behavior as a function of neighborhood surroundings (geographical momentary assessment; GMA), we collected time-stamped GPS data and ecological momentary assessment (EMA) ratings of mood, stress, and drug craving over 16 weeks at randomly prompted times during the waking hours of opioid-dependent polydrug users receiving methadone maintenance. Locations of EMA entries and participants' travel tracks calculated for the 12 before each EMA entry were mapped. Associations between subjective ratings and objective environmental ratings were evaluated at the whole neighborhood and 12-h track levels.Participants (N=27) were compliant with GMA data collection; 3711 randomly prompted EMA entries were matched to specific locations. At the neighborhood level, physical disorder was negatively correlated with negative mood, stress, and heroin and cocaine craving (ps.0001-.0335); drug activity was negatively correlated with stress, heroin and cocaine craving (ps .0009-.0134). Similar relationships were found for the environments around respondents' tracks in the 12h preceding EMA entries.The results support the feasibility of GMA. The relationships between neighborhood characteristics and participants' reports were counterintuitive and counter-hypothesized, and challenge some assumptions about how ostensibly stressful environments are associated with lived experience and how such environments ultimately impair health. GMA methodology may have applications for development of individual- or neighborhood-level interventions.