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Background Treatment with opioid agonists is effective for opioid use disorder, but early discontinuation of treatment is a major obstacle to success. Intensive longitudinal methods — which take many repeated measurements over time, usually in the field— have provided unique insight into the effects of stress, mood and craving on drug use while people are being treated; these methods might also be useful for studying the processes that lead people to drop out of treatment. Methods Ecological momentary assessment (EMA) was conducted for up to 17 weeks by obtaining multiple electronic diary entries per day from 238 participants being treated with methadone or buprenorphine-naloxone. Survival analysis was used to study two outcomes: dropping out of treatment and noncompliance with EMA self-report requirements. Self-reports of stress, craving, and mood were used as time-varying predictors. Demographic and psychosocial variables measured with the Addiction Severity Index at the start of treatment were used as time-invariant predictors. Results Dropping out of treatment was more likely in participants with more reported hassles (a measure of stress), higher levels of cocaine craving, lower levels of positive mood, a recent history of emotional abuse, a recent history of being bothered frequently by psychological problems, and with buprenorphine rather than methadone as their medication. In contrast, study noncompliance was not significantly associated with any of the variables analyzed. Conclusions Assessment of stress, craving and mood during treatment might identify people who are at greater risk of dropping out, and therapeutic interventions targeting these processes might increase retention.

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.

Knowing how stress manifests in the lives of people with substance-use disorders could help inform mobile “just in time” treatment. The purpose of this paper is to examine discrete episodes of stress, as distinct from the fluctuations in background stress assessed in most EMA studies. For up to 16 weeks, outpatients on opioid-agonist treatment carried smartphones on which they initiated an entry whenever they experienced a stressful event (SE) and when randomly prompted (RP) three times daily. Participants reported the severity of stress and craving and the context of the report (location, activities, companions). Decomposition of covariance was used to separate within-person from between-person effects; r effect sizes below are within-person. Participants (158 of 182; 87%) made 1787 stress-event entries. Craving for opioids increased with stress severity (r effect = 0.50). Stress events tended to occur in social company (with acquaintances, 0.63, friends, 0.17, or on the phone, 0.41) rather than with family (spouse, −0.14; child, −0.18), and in places with more overall activity (bars, 0.32; outside, 0.28; walking, 0.28) and more likelihood of unexpected experiences (with strangers, 0.17). Being on the internet was slightly protective (−0.22). Our prior finding that being at the workplace protects against background stress in our participants was partly supported in these stressful-event data. The contexts of specific stressful events differ from those we have seen in prior studies of ongoing background stress. However, both are associated with drug craving.

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.

Responses to stress and drug craving differ between men and women. Differences in the momentary experience of stress in relation to craving are less well-understood.Using ecological momentary assessment (EMA), we examined sex differences in real-time in two areas: (1) causes and contexts associated with stress, and (2) the extent to which stress and drug cues are associated with craving.Outpatients on opioid-agonist treatment (135 males, 47 females) reported stress, craving, and behavior on smartphones for 16 weeks. They initiated an entry each time they felt more stressed than usual (stress event) and made randomly prompted entries 3 times/day. In stress-event entries, they identified the causes and context (location, activity, companions), and rated stress and craving severity.The causes reported for stress events did not differ significantly by sex. Women reported arguing and being in a store more often during stress events, and men reported working more often during stress events, compared to base rates (assessed via random prompts). Women showed a greater increase in opioid craving as a function of stress (p 0.0001) and had higher stress ratings in the presence of both stress and drug cues relative to men (p 0.01). Similar effects were found for cocaine craving in men (p 0.0001).EMA methods provide evidence based on real-time activities and moods that opioid-dependent men and women experience similar contexts and causes for stress but differ in stress- and cue-induced craving. These findings support sex-based tailoring of treatment, but because not all participants conformed to the overall pattern of sex differences, any such tailoring should also consider person-level differences.

RATIONALE: Ecological momentary assessment (EMA) of specific events usually focuses more on antecedents and concomitants than on aftermaths. OBJECTIVES: To examine mental state both before and after discrete episodes of stress and drug use. METHODS: For up to 16 weeks, outpatients on opioid-agonist treatment carried smartphones on which they initiated entries for stressful events (SEs) or lapses to drug use (DUs), and thrice daily when randomly prompted (RPs). Participants rated their stress, opioid craving, cocaine craving, and moods. RP entries within 5 hours of an event were analyzed and compared to other RPs. RESULTS: Stress, negative mood, and craving were generally higher before and after DUs and SEs compared to background levels in participants with at least one DU (n=149) or SE (n=158). Before DUs, there were increases in negative mood, opioid craving, and cocaine craving, but not background stress. Before SEs, there were increases in background stress, opioid craving, and cocaine craving, but not negative mood. These changes were more variable after events than before. Neither DUs nor SEs were significantly related to positive mood. CONCLUSIONS: Stress increased before stressful-event entries, but was less evident before drug use. Craving increased in the hours before drug use and stressful events—and remained elevated in the hours after either event. These results suggest a stronger link between drug use and craving than between drug use and stress. Lapses to drug use did not improve mood or reduce stress, at least not at our one-hour-bin time resolution, suggesting that if such benefits exist, they are brief.

Infection with hepatitis C virus (HCV) is a complex public health problem with a high prevalence of chronic infection, an increasing prevalence of HCV-associated disease, low rates of testing and treatment, and the prospect of increasing incidence associated with intravenous drug use (IVDU; Smith, Jorgensen, Zibbell, & Beckett, 2012). IVDU is a major risk factor for HCV, and HCV prevalence is exceedingly high among intravenous drug users (Schreuder et al., 2010). A study conducted in Baltimore, MD, found that the seroprevalence of HCV among intravenous drug users was 77%, with most individuals becoming positive within the first year of initiating IVDU (Garfein, Vlahov, Galai, Doherty, & Nelson, 1996). IVDU does not directly influence HCV progression despite the potential for multiple repeat exposures to various HCV genotypes, but HCV progression may be accelerated by several factors associated with IVDU, including excess alcohol intake, reduced access and adherence to treatment, and poor nutrition (Cooper & Mills, 2006). Given the adverse public health consequences of HCV infection and its link to HIV, improved approaches to reducing the spread of HCV, particularly among intravenous drug users, are needed. Although there is strong evidence that medication-assisted addiction treatment reduces drug misuse, HIV-risk behaviors, and HIV infection rates (Metzger, Woody, & O’Brien, 2010; Millson et al., 2007), the corresponding evidence for HCV remains controversial (Crofts, Nigro, Oman, Stevenson, & Sherman, 1997; Selvey, Denton, & Plant, 1997; Thiede, Hagan, & Murrill, 2000), suggesting that approaches beyond medication-assisted treatment alone are needed to curb HCV-risk behaviors and infection rates. Given that risk behaviors persist during addiction treatment (Chaudhry et al., 2011) and are more likely among patients who do not know their HCV status (Vidal-Trecan, Coste, Varescon-Pousson, Christoforov, & Boissonnas, 2000), one approach might be to test people for hepatitis C upon addiction-treatment admission and inform them of the results. Unawareness of HCV status is common. In one study, 72% of HCV+ and 46% of HCV− intravenous drug users were unaware of their HCV status (Hagan et al., 2006). However, even after diagnosis with HCV, high-risk behaviors continue (Hagan et al., 2006; Ompad, Fuller, Vlahov, Thomas, & Strathdee, 2002). The initial diagnosis of HCV had a strong, negative emotional effect in almost half of a patient group that was not primarily composed of intravenous drug users (Fabris et al., 2006). For intravenous drug users, an HCV diagnosis is sometimes thought to be less momentous than for nonintravenous drug users, but that may not always be true (Treloar & Rhodes, 2009). As for possible emotional effects of the disease process itself, there seems to be no published research; phenomenological studies of hepatitis C focus on patients who have begun antiviral treatment, which can produce psychiatric side effects of its own (Sgorbini, O’Brien, & Jackson, 2009). What is unknown is whether ongoing risk behavior is increased by the negative emotional effect of HCV diagnosis itself or by other factors in the lived experience of HCV+ individuals not on antiviral treatment. The analyses presented here are part of a project to better understand the factors influencing drug use and lapse and improve approaches to reducing high-risk behaviors. We have followed up on prior research in our laboratory showing that HCV+ patients in methadone maintenance report higher drug-related HIV-risk behaviors and are more likely to test positive for opioids compared with HCV− patients (Willner-Reid, Belendiuk, Epstein, Schmittner, & Preston, 2008). Our treatment-research clinic uses ecological momentary assessment (EMA), a technique for collection of in-the-field, first-person data using handheld computers. EMA largely eliminates recall bias by collecting self-report in near real time and produces time-stamped data that are amenable to statistical aggregation (Shiffman, Stone, & Hufford, 2008). We have previously reported success with EMA in a study of over 100 heroin- and cocaine-using methadone-maintained patients and shown that cocaine-use events are preceded by increasing exposure to drug-use triggers and are associated with craving, stress, and tobacco use (Epstein, Marrone, Heishman, Schmittner, & Preston, 2010; Epstein & Preston, 2010; Epstein et al., 2009; Preston et al., 2009). In the analyses reported here, we determine whether HCV+ and HCV− individuals are differentially exposed, in their daily lives, to triggers of craving and drug use, and we explore the relationship of HCV status with demographics and momentary moods in patients whose HCV is not yet overtly symptomatic in an effort to inform treatment interventions for reduction of HCV-risk behavior and infection rates.

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.

The study of craving and lapse during attempts to quit smoking has been quietly revolutionized by the use of handheld data-collection devices that enable study participants to report, in real time, their activities and moods in their daily environments1. This methodology is referred to as experience sampling2 or Ecological Momentary Assessment (EMA)3. A PDA (Personal Digital Assistant or PalmPilot) configured for use in EMA is referred to as an Electronic Diary (ED). EMA comprises two complementary types of data collection. The first type occurs through random prompts, enabling assessment of the base rates of exposure to putative craving/lapse triggers such as stressors and drug-associated cues4. The second type of data collection is participant-initiated; participants are typically instructed to initiate an EMA entry immediately after each episode of craving or use. These event-driven data provide near-real-time self-report of such episodes. EMA data collected through random prompts enable a truly prospective approach to the question of what events preceded a specific episode of use. For example, Shiffman and Waters5 use such data to show that lapses to cigarette smoking were preceded by increases in negative affect over a time course of hours, but not days—in other words, over a time frame that could not have been captured if participants had merely made daily visits to a laboratory for assessment. EMA studies of illicit-drug use are far more rare. For example, to determine whether stress predicts relapse to cocaine or heroin use, there is only a small body of non-EMA prospective studies whose time frames were not sensitive to episodes of acute stress. The general finding from such studies has been that prospective measures of stress can predict relapse only when aggregated over time frames of three to twelve months, not week by week6–8. The effects of more rapid increases in stress cannot be determined without EMA data. The near-absence of EMA studies presumably reflects reluctance to entrust handheld electronic devices to individuals from the relevant populations, along with concern that meaningful real-time reports cannot be collected during use of intoxicating drugs. However, some studies have shown that EMA is possible in users of illicit drugs, providing new insights into the natural history of Ecstasy use9 and demonstrating that cannabis smokers10 and homeless users of crack cocaine11 will use and return cellphones issued for EMA recording. Larger datasets would help to resolve longstanding theoretical questions about the precipitants and process of drug craving and use, and may also lead to better outcome measurement in clinical trials12 and even to new forms of tailored, on-the-spot treatment interventions (see Comment). In this study, we used EMA to monitor craving for, and use of, cocaine and heroin in a large sample of methadone-maintained outpatients. (Methadone maintenance, though highly effective, does not entirely eliminate heroin use in all patients.) Here we present data on the time course of mood and cue exposure in the hours before self-reported episodes of craving and drug use.