Effects of kratom on driving: Results from a cross-sectional survey, ecological momentary assessment, and pilot simulated driving Study.

OBJECTIVES: Despite widespread kratom use, there is a lack of knowledge regarding its effects on driving. We evaluated the self-reported driving behaviors of kratom consumers and assessed their simulated-driving performance after self-administering kratom products. METHODS: We present results from: 1) a remote, national study of US adults who regularly use kratom, and 2) an in-person substudy from which we re-recruited participants. In the national study (N = 357), participants completed a detailed survey and a 15-day ecological momentary assessment (EMA) that monitored naturalistic kratom use. For the remote study, outcomes were self-reported general and risky driving behaviors, perceived impairment, and driving confidence following kratom administration. For the in-person substudy, 10 adults consumed their typical kratom products and their driving performance on a high-fidelity driving simulator pre- and post-kratom administration was evaluated. RESULTS: Over 90% of participants surveyed self-reported driving under the influence of kratom. Most reported low rates of risky driving behavior and expressed high confidence in their driving ability after taking kratom. This was consistent with EMA findings: participants reported feeling confident in their driving ability and perceived little impairment within 15-180 min after using kratom. In the in-person substudy, there were no significant changes in simulated driving performance after taking kratom. CONCLUSIONS: Using kratom before driving appears routine, however, self-reported and simulated driving findings suggest kratom effects at self-selected doses among regular kratom consumers do not produce significant changes in subjective and objective measures of driving impairment. Research is needed to objectively characterize kratom's impact on driving in regular and infrequent consumers.

Delay of punishment highlights differential vulnerability to developing addiction-like behavior toward sweet food.

Resistance to punishment is commonly used to measure the difficulty in refraining from rewarding activities when negative consequences ensue, which is a hallmark of addictive behavior. We recently developed a progressive shock strength (PSS) procedure in which individual rats can titrate the amount of punishment that they are willing to tolerate to obtain food rewards. Here, we investigated the effects of a range of delays (0-12 s) on resistance to punishment measured by PSS break points. As expected from delay discounting principles, we found that delayed shock was less effective as a punisher, as revealed by higher PSS breakpoints. However, this discounting effect was not equally distributed in the population of rats, and the introduction of a delay highlighted the existence of two populations: rats that were sensitive to immediate punishment were also sensitive to delayed shock, whereas rats that were resistant to immediate punishment showed strong temporal discounting of delayed punishment. Importantly, shock-sensitive rats suppressed responding even in subsequent non-punishment sessions, and they differed from shock-resistant rats in anxiety-like behavior, but not in sensitivity to pain. These results show that manipulation of temporal contingencies of punishment in the PSS procedure provides a valuable tool to identify individuals with a double vulnerability to addiction: low sensitivity to aversion and excessive discounting of negative future consequences. Conversely, the shock-sensitive population may provide a model of humans who are vulnerable to opportunity loss due to excessive anxiety.

Ecological Momentary Assessment of Self-Reported Kratom Use, Effects, and Motivations Among US Adults.

Importance: Kratom products, which are sold legally in most of the US, contain alkaloids with opioidergic, adrenergic, and serotonergic activity. Millions of people use kratom to relieve pain, improve mood, or self-manage substance use disorders (SUDs). Kratom use has primarily been examined via surveys, in which recall biases among satisfied users may lead to minimization of transient negative outcomes. Further prospective study of kratom use, such as with ecological momentary assessment (EMA), is needed. Objective: To characterize proximal motivators, effects, and patterns of kratom use and to assess whether use frequency is associated with motivations, effects, past-year criteria for SUD for kratom (KUD), or other substance use. Design, Setting, and Participants: For this prospective cross-sectional study, an intensive longitudinal smartphone-based EMA in which participants' current behaviors and experiences were repeatedly sampled in real time was conducted between July 1 and October 31, 2022. Participants comprised a convenience sample of US adults who used kratom at least 3 days per week for at least 4 weeks at the time of online screening. Criteria for past-year KUD were based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Data analysis was performed between November 2022 and November 2023. Exposure: The exposure was 13 401 kratom-use events across 15 days. Main Outcomes and Measures: A baseline survey covering demographics, health, kratom attitudes and behaviors, use motivations, other substance use, and KUD was administered before EMA. Data for the following EMA entries were then collected: event-contingent entries for kratom use (product, dose, and proximal motivations), follow-up entries (short-term effects and consequences of use events), random-prompt entries (mood), beginning-of-day entries (effects of kratom on sleep), and end-of-day entries (daily subjective descriptions of kratom effects). Bayesian regression was used to estimate means and credible intervals. Results: A total of 357 participants completed the EMA. Their mean (SD) age was 38.0 (11.1) years; more than half were men (198 [55.5%]). Participants reported overall motivators of use on the baseline survey that involved managing psychiatric and SUD problems, but proximal motivators evaluated during the EMA involved situation-specific needs such as increasing energy and productivity and decreasing pain. Acute effects were considered congruent with daily obligations. Use patterns, despite having some distinguishing features, were generally similar in their motivators and effects; participants used kratom predominantly during the daytime and seemed to find use frequencies that suited their needs. Higher use patterns were associated with symptoms of physical dependence (eg, withdrawal or tolerance). Co-used substances included caffeine, nicotine, vitamins, and cannabis. Conclusions and Relevance: Most participants in this study reported using kratom in a seemingly nonproblematic way. When such use appeared problematic, the key element was usually that withdrawal avoidance became a proximal motivator. Longitudinal studies examining changes in kratom use patterns and effects over time are needed.

Novel methods for the remote investigation of emerging substances: Application to kratom.

The botanical product commonly called "kratom" is still relatively novel to the United States. Like other natural products marketed as supplements, kratom is highly variable, both in terms of the alkaloids naturally occurring in kratom leaves and in terms of processing and formulation. Kratom products sold in the United States are not well-characterized, nor are daily use patterns among regular users. Surveys and case reports have comprised most of the literature on kratom use among humans. To advance our understanding of real-world kratom use, we developed a protocol for the remote study of regular kratom-using adults in the United States. Our study had three aspects implemented in one pool of participants nationwide: an in-depth online survey, 15 days of ecological momentary assessment (EMA) via smartphone app, and the collection and assay of the kratom products used by participants during EMA. Here, we describe these methods, which can be used to investigate myriad drugs or supplements. Recruiting, screening, and data collection occurred between July 20, 2022 and October 18, 2022. During this time, we demonstrated that these methods, while challenging from a logistical and staffing standpoint, are feasible and can produce high-quality data. The study achieved high rates of enrollment, compliance, and completion. Substances that are emerging or novel, but still largely legal, can be productively studied via nationwide EMA combined with assays of shipped product samples from participants. We discuss challenges and lessons learned so other investigators can adapt these methods. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Activity space during treatment with medication for opioid use disorder: Relationships with personality, mood, and drug use.

INTRODUCTION: Activity space in people with substance use disorders (SUDs) has been assessed for theoretical reasons and for detection/prevention of relapse. In this observational study, we relate passively obtained activity space measures to mental states and behaviors relevant to the success of treatment for opioid use disorder. Our long-term goal is to use such data to assess risk in real time and to recognize when SUD patients might benefit from a just-in-time intervention. METHODS: We used GPS data from 238 urban residents in the first 16 weeks of stabilization on medication for opioid use disorder to test preregistered hypotheses about activity space (distance traveled, number of locations, time spent moving, and psychosocial-hazard levels of neighborhoods where participants spent time) in relation to certain static variables (personality, mood propensities) and time-varying treatment-relevant behaviors such as craving and use of opioids and cocaine. RESULTS: The most consistent findings were that 1) mobility decreased over the course of the study; 2) neuroticism was associated with overall lower mobility; 3) trait-like positive mood (averaged from momentary ratings) was associated with higher mobility; 4) participants who used cocaine more frequently had lower mobility; 5) early in treatment, participants spent less time moving (i.e., were more sedentary) on days when they were craving. Some of these findings were in the expected direction (i.e., the ones involving neuroticism and positive mood), and some were opposite to the expected direction (i.e., we expected cocaine use to be associated with higher mobility); others (e.g., changes in mobility over time or in relation to craving) involved nondirectional hypotheses. CONCLUSIONS: Real-time information that patients actively provide is valuable for assessing their current state, but providing this information can be burdensome. The current results indicate that certain static or passively obtained data (personality variables and GPS-derived mobility information) are relevant to time-varying, treatment-relevant mental states and drug-related behavior, and therefore might be useful when incorporated into algorithms for detecting need for intervention in real time. Further research should assess how population-specific these relationships are, and how these passive measures can best be combined with low temporal-density, actively-provided data to obtain valid, reliable assessments with minimal burden.

Health Outcomes by Neighborhood (HON): Effects of Neighborhood, Social Instability, and Health Factors on 12-Month Trajectories of Substance-Use Disorder Symptoms.

BACKGROUND: Previous studies have shown that environment and health can influence drug use trajectories and the effects of substance use disorder (SUD) treatments. We hypothesized that trajectories of drug use-related problems, based on changes in DSM-5 symptoms, would vary by type(s) of drugs used, health factors, and neighborhood characteristics. METHODS: We assessed mental and physical health, stress, social instability, neighborhood characteristics (disorderliness and home value), and DSM-5 symptom counts at two study visits, 12 months apart, in a community sample (baseline N = 735) in Baltimore, MD. Three prominent categories of drug-use trajectory were identified with K-means cluster analysis of symptom counts: Persistent (4 or more symptoms at both visits or at Visit 2), Improved (decrease from 4 or more symptoms at Visit 1 to 3 or fewer symptoms at Visit 2), and Low-Stable (3 or fewer symptoms at both visits). Baseline health and neighborhood measures were tested as predictors of trajectory in mediation and moderation models. RESULTS: Among people with current opioid- and/or stimulant-use, odds of an Improved trajectory were (1) decreased with neighborhood disorder and social instability, or (2) increased with home value and social instability. Odds of a Low-Stable trajectory were decreased by social instability and stress but increased in those who were older or self-identified as white. CONCLUSIONS: Trajectories of drug use-related problems are influenced by sociodemographic variables, neighborhood factors, and health. Assessing DSM-5 symptom counts as an outcome measure may be valuable in monitoring or predicting long-term trajectories and treatment effectiveness.

A self-adjusting, progressive shock strength procedure to investigate resistance to punishment: Characterization in male and female rats.

Indifference to harmful consequences is one of the main characteristics of compulsive behaviors and addiction. Animal models that provide a rapid and effective measure of resistance to punishment could be critical for the investigation of mechanisms underlying these maladaptive behaviors. Here, analogous to the progressive ratio (PR) procedure widely used to evaluate appetitive motivation as the response requirement is increased, we developed a self-adjusting, progressive shock strength (PSS) procedure. The PSS provides, within a single session, a break point that quantifies the propensity to work for a reward in spite of receiving electric footshock that progressively increases in duration. In both male and female rats, the PSS break point was sensitive to 1) hunger; and 2) changes in the qualitative, but not quantitative, incentive value of the reward. In systematic comparisons between PSS and PR procedures in the same rats, we found that both measures are sensitive to manipulations of motivational states, but they are not intercorrelated, suggesting that they measure overlapping but partially distinct processes. Importantly, the PSS procedure represents a refinement in the 3Rs principles of animal research because animals can control the strength of shock that they are willing to tolerate. This self-adjusting PSS procedure may represent a useful tool to investigate mechanisms underlying maladaptive behavior that persists in certain individuals despite harmful consequences.

Variability in intensively assessed mood: Systematic sources and factor structure in outpatients with opioid use disorder.

In intensive longitudinal studies using ecological momentary assessment, mood is typically assessed by repeatedly obtaining ratings for a large set of adjectives. Summarizing and analyzing these mood data can be problematic because the reliability and factor structure of such measures have rarely been evaluated in this context, which-unlike cross-sectional studies-captures between- and within-person processes. Our study examined how mood ratings (obtained thrice daily for 8 weeks; n = 306, person moments = 39,321) systematically vary and covary in outpatients receiving medication for opioid use disorder (MOUD). We used generalizability theory to quantify several aspects of reliability, and multilevel confirmatory factor analysis (MCFA) to detect factor structures within and across people. Generalizability analyses showed that the largest proportion of systematic variance across mood items was at the person level, followed by the person-by-day interaction and the (comparatively small) person-by-moment interaction for items reflecting low arousal. The best-fitting MCFA model had a three-factor structure both at the between- and within-person levels: positive mood, negative mood, and low-arousal states (with low arousal considered as either a separate factor or a subfactor of negative mood). We conclude that (a) mood varied more between days than between moments and (b) low arousal may be worth scoring and reporting separately from positive and negative mood states, at least in a MOUD population. Our three-factor structure differs from prior analyses of mood; more work is needed to understand the extent to which it generalizes to other populations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Being at work improves stress, craving, and mood for people with opioid use disorder: Ecological momentary assessment during a randomized trial of experimental employment in a contingency-management-based therapeutic workplace.

Employment problems are common among people with substance use disorders (SUDs), and improving vocational functioning is an important aspect of SUD treatment. More detailed understanding of the psychosocial benefits of employment may help refine vocational interventions for people with SUDs. Here, we used ecological momentary assessment to measure possible affective improvements associated with work. Participants (n = 161) with opioid use disorder were randomized to work (job-skills training) in a contingency-management-based Therapeutic Workplace either immediately or after a waitlist delay. Throughout, participants responded via smartphone to randomly scheduled questionnaires. In linear mixed models comparing responses made at work vs. all other locations, being at work was associated with: less stress, less craving for opioids and cocaine, less negative mood, more positive mood, and more flow-like states. Some of these differences were also observed on workdays vs. non-workdays outside of work hours. These results indicate that benefits associated with work may not be restricted to being actually in the workplace; however, randomization did not reveal clear changes coinciding with the onset of work access. Overall, in contrast to work-associated negative moods measured by experience-sampling in the general population, Therapeutic Workplace participants experienced several types of affective improvements associated with work.

Nonfatal opioid overdoses before and after Covid-19: Regional variation in rates of change.

BACKGROUND: The Covid-19 pandemic and its accompanying public-health orders (PHOs) have led to (potentially countervailing) changes in various risk factors for overdose. To assess whether the net effects of these factors varied geographically, we examined regional variation in the impact of the PHOs on counts of nonfatal overdoses, which have received less attention than fatal overdoses, despite their public health significance. METHODS: Data were collected from the Overdose Detection Mapping Application Program (ODMAP), which recorded suspected overdoses between July 1, 2018 and October 25, 2020. We used segmented regression models to assess the impact of PHOs on nonfatal-overdose trends in Washington DC and the five geographical regions of Maryland, using a historical control time series to adjust for normative changes in overdoses that occurred around mid-March (when the PHOs were issued). RESULTS: The mean level change in nonfatal opioid overdoses immediately after mid-March was not reliably different in the Covid-19 year versus the preceding control time series for any region. However, the rate of increase in nonfatal overdose was steeper after mid-March in the Covid-19 year versus the preceding year for Maryland as a whole (B = 2.36; 95% CI, 0.65 to 4.06; p = .007) and for certain subregions. No differences were observed for Washington DC. CONCLUSIONS: The pandemic and its accompanying PHOs were associated with steeper increases in nonfatal opioid overdoses in most but not all of the regions we assessed, with a net effect that was deleterious for the Maryland region as a whole.

Were self-described introverts "immune" to increased drug use and entrapment during the pandemic?

BACKGROUND: Social restrictions and other stressors related to the Covid-19 pandemic disrupted daily life in ways that might have increased drug use and undermined mental health. We investigated whether such changes depended on the amount and quality of a person's social activity. We also evaluated the popular idea that effects of pandemic-related restrictions would depend on introversion; to this end, we used self-described introversion as a proxy for preferred frequency of social activity. METHODS: Between September 2020 and March 2021, we obtained online-survey data from 2615 respondents who retrospectively reported alcohol, opioid, or psychostimulant use. We analyzed (1) changes in drug use and entrapment (a psychological construct linked to suicidality) as a function of introversion and the frequency and quality of social activity, and (2) changes in drug use as a function of change in entrapment. RESULTS: Most felt more entrapped during the pandemic, but only a minority increased drug use. Generally: (1) entrapment and drug use increased in respondents unsatisfied with their social activity, (2) introversion and frequency of activity had less influence than satisfaction, (3) introverts reported more symptoms of entrapment, anxiety, depression, and loneliness than non-introverts, (4) when social activity was frequent and unsatisfying, psychostimulant use increased in introverts and opioid use increased in extraverts, (5) alcohol use increased in those who felt increased entrapment, and (6) alcohol and opioid use decreased in those who felt decreased entrapment. CONCLUSIONS: Satisfactory social activity (even in small amounts) was associated with better outcomes, mostly without regard to introversion.

Trajectories of craving during medication-assisted treatment for opioid-use disorder: Subtyping for early identification of higher risk.

AIMS: To examine evidence for subtypes of opioid craving trajectories during medication for opioid use disorder (MOUD), and to (a) test whether these subtypes differed on MOUD-related outcomes, and (b) determine whether nonresponders could be identified before treatment initiation. DESIGN, SETTING, AND PARTICIPANTS: Outpatients (n = 211) being treated with buprenorphine or methadone for up to 16 weeks. Growth mixture modeling was used to identify unobserved craving-trajectory subtypes. Support Vector Machines (SVM) were trained to predict subtype membership from pretreatment data. MEASUREMENTS: Self-reported opioid craving (Ecological Momentary Assessment - EMA - three random moments per day). Participant-initiated EMA reports of drug use or higher-than-usual stress. Addiction Severity Index (ASI) pretreatment. FINDINGS: Four craving trajectories were identified: Low (73%); High and Increasing (HIC) (10.9%); Increasing and Decreasing (8.5%); and Rapidly Declining (7.6%). The HIC subgroup reported the highest use of heroin, any opiate, and cannabis during treatment. The Low Craving subgroup reported the lowest use of heroin or any opiate use, and the lowest levels of stress and drug-cue exposure during treatment. SVM models predicting HIC membership before treatment initiation had a sensitivity of 0.70, specificity of 0.78, and accuracy of 0.77. Including 3 weeks of EMA reports increased sensitivity to 0.78, specificity to 0.84, and accuracy to 0.85. CONCLUSIONS: Subgroups of MOUD patients show distinct patterns of opioid craving during treatment. Subgroups differ on critical outcomes including drug-use lapse, stress, and exposure to drug cues. Data from enrollment and early in treatment may help focus clinical attention.

I feel good? Anhedonia might not mean "without pleasure" for people treated for opioid use disorder.

Anhedonia is usually defined as partial or total loss of the capacity for pleasure. People with anhedonia in the context of major depressive disorder may have an unexpected capacity for event-related mood brightening, observable when mood is assessed dynamically (with smartphone-based ecological momentary assessment [EMA]) rather than only statically via questionnaire. We used EMA to monitor mood and pleasant events for 4 weeks in 54 people being treated with opioid agonist medication for opioid-use disorder (OUD), which is also associated with anhedonia, said to manifest especially as loss of pleasure from nondrug reward. We compared OUD patients' EMA reports with those of 47 demographically similar controls. Background positive mood was lower in OUD patients than in controls, as we hypothesized (Cohen ds = .85 to 1.32, 95% CIs [.66, 1.55]), although, contrary to our hypothesis, background negative mood was also lower (ds = .82 to .85, 95% CIs [.73, .94]). As hypothesized, instances of nondrug pleasure were as frequent in OUD patients as in controls-and were not rated much less pleasurable (d = .18, 95% CI [-.03, .35]). Event-related mood brightening occurred in both abstinent and nonabstinent OUD patients (ds = .18 to .37, CIs [-.01, .57]) and controls (ds = .04 to .60, CIs [-.17, .79]), brightening before each event began earlier for controls than OUD patients, but faded similarly postevent across groups. Our findings add to the evidence that anhedonia does not rule out reactive mood brightening, which, for people with OUD being treated on opioid agonist medication, can be elicited by nondrug activities. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The protective effect of operant social reward on cocaine self-administration, choice, and relapse is dependent on delay and effort for the social reward.

Social reinforcement-based treatments are effective for many, but not all, people with addictions to drugs. We recently developed an operant rat model that mimics features of one such treatment, the community-reinforcement approach. In this model, rats uniformly choose social interaction over methamphetamine or heroin. Abstinence induced by social preference protects against the incubation of drug-seeking that would emerge during forced abstinence. Here, we determined whether these findings generalize to cocaine and whether delaying or increasing effort for social interaction could reveal possibly human-relevant individual differences in responsiveness. We trained male and female rats for social self-administration (6 days) and then for cocaine self-administration, initially for 2-h/day for 4 days, and then for 12-h/day continuously or intermittently for 8 days. We assessed relapse to cocaine seeking after 1 and 15 days. Between tests, the rats underwent either forced abstinence or social-choice-induced abstinence. After establishing stable social preference, we manipulated the delay for both rewards or for social reward alone, or the response requirements (effort) for social reward. Independent of cocaine-access conditions and sex, operant social interaction inhibited cocaine self-administration and prevented incubation of cocaine seeking. Preference for social access was decreased by the delay of both rewards or social reward alone, or by increased response requirements for social reward, with notable individual variability. This choice procedure can identify mechanisms of individual differences in an animal model of cocaine use and could thereby help screen medications for people who are relatively unresponsive to treatments based on rewarding social interaction.

Longitudinal patterns of momentary stress during outpatient opioid agonist treatment: A growth-mixture-model approach to classifying patients.

BACKGROUND: We previously showed, in people starting treatment for opioid use disorder (OUD), that stress is neither necessary nor sufficient for lapses to drug use to occur, despite an association between the two. Both theoretical clarity and case-by-case prediction accuracy may require initial differentiation among patients. AIM: To examine: (a) evidence for distinct overall trajectories of momentary stress during OUD treatment, (b) relationships between stress trajectory and treatment response, and (c) relationships between stress trajectory and momentary changes in stress and craving prior to lapses. METHODS: We used ecological momentary assessment (EMA) to collect ratings of stress and craving 3x/day for up to 16 weeks in 211 outpatients during agonist treatment for OUD. With growth mixture models, we identified trajectories of stress. We used mixed effect models to examine trajectory-group differences in the dynamics of stress and craving just before lapses to any drug use. RESULTS: We identified four trajectories of stress: Increasing (13.7 %); Moderate and Stable (23.7 %); Declining and Increasing (18 %); and Low (44.6 %). Overall drug use and opioid craving were lowest in the Low Stress group. Overall drug use was highest in the Moderate and Stable group. Alcohol use and opioid craving were highest in the Increasing Stress group. Opioid craving increased before lapse for most groups, but stress increased before lapses for only the Moderate and Stable group. CONCLUSION: There are natural groupings of participants with distinct patterns of stress severity during OUD treatment. Momentary stress/craving/lapse associations may be better characterized when these groupings are considered first.

Beyond abstinence and relapse II: momentary relationships between stress, craving, and lapse within clusters of patients with similar patterns of drug use.

RATIONALE: Given that many patients being treated for opioid-use disorder continue to use drugs, identifying clusters of patients who share similar patterns of use might provide insight into the disorder, the processes that affect it, and ways that treatment can be personalized. OBJECTIVES AND METHODS: We applied hierarchical clustering to identify patterns of opioid and cocaine use in 309 participants being treated with methadone or buprenorphine (in a buprenorphine-naloxone formulation) for up to 16 weeks. A smartphone app was used to assess stress and craving at three random times per day over the course of the study. RESULTS: Five basic patterns of use were identified: frequent opioid use, frequent cocaine use, frequent dual use (opioids and cocaine), sporadic use, and infrequent use. These patterns were differentially associated with medication (methadone vs. buprenorphine), race, age, drug-use history, drug-related problems prior to the study, stress-coping strategies, specific triggers of use events, and levels of cue exposure, craving, and negative mood. Craving tended to increase before use in all except those who used sporadically. Craving was sharply higher during the 90 min following moderate-to-severe stress in those with frequent use, but only moderately higher in those with infrequent or sporadic use. CONCLUSIONS: People who share similar patterns of drug-use during treatment also tend to share similarities with respect to psychological processes that surround instances of use, such as stress-induced craving. Cluster analysis combined with smartphone-based experience sampling provides an effective strategy for studying how drug use is related to personal and environmental factors.

Quality of life during a randomized trial of a therapeutic-workplace intervention for opioid use disorder: Web-based mobile assessments reveal effects of drug abstinence and access to paid work.

Background: Employment and improved quality of life (QOL) are, separately, valued outcomes of substance use disorder (SUD) treatment. It is also important to understand QOL changes caused by employment itself; therefore, we assessed QOL during a randomized trial of a contingency-management-based Therapeutic Workplace for people with opioid use disorder. Methods: For 12 weeks, participants (n = 61) responded to QOL questionnaires in a mobile web app accessed with study-issued smartphones. At enrollment, participants were randomized to work in the Therapeutic Workplace immediately (immediate work group, IWG) or after a 3-week waitlist delay (delayed work group, DWG). Once both groups could work, wage-resetting contingencies were introduced for their opiate- and cocaine-urinalysis. Data were analyzed by (1) access to work with and without contingencies and (2) overall urinalysis-verified opiate- and cocaine-abstinence. Results: DWG and/or IWG reported improvements in several QOL areas (sleep, transportation, recreation); however, they also reported increased money-related difficulties and less time spent with friends/family. These changes did not coincide with DWG's work access, but some (more sleep, money-related difficulties) coincided with the urinalysis contingencies. Greater opiate- and/or cocaine-abstinence was also associated with several improvements: sleep, paying bills, time spent with friends/family, and exercising. Surprisingly, intermediate cocaine abstinence was associated with reductions in work-capacity satisfaction and recreation. Conclusions: Participants reported complex QOL differences during their experimental employment and associated with drug abstinence. Future work should help participants address issues that may be relevant to employment generally (e.g., time with friends/family) or contingency management specifically (e.g., money-related issues for non-abstinent participants).

Beyond abstinence and relapse: cluster analysis of drug-use patterns during treatment as an outcome measure for clinical trials.

RATIONALE: Many people being treated for opioid use disorder continue to use drugs during treatment. This use occurs in patterns that rarely conform to well-defined cycles of abstinence and relapse. Systematic identification and evaluation of these patterns could enhance analysis of clinical trials and provide insight into drug use. OBJECTIVES: To evaluate such an approach, we analyzed patterns of opioid and cocaine use from three randomized clinical trials of contingency management in methadone-treated participants. METHODS: Sequences of drug test results were analyzed with unsupervised machine-learning techniques, including hierarchical clustering of categorical results (i.e., whether any samples were positive during each week) and K-means longitudinal clustering of quantitative results (i.e., the proportion positive each week). The sensitivity of cluster membership as an experimental outcome was assessed based on the effects of contingency management. External validation of clusters was based on drug craving and other symptoms of substance use disorder. RESULTS: In each clinical trial, we identified four clusters of use patterns, which can be described as opioid use, cocaine use, dual use (opioid and cocaine), and partial/complete abstinence. Different clustering techniques produced substantially similar classifications of individual participants, with strong above-chance agreement. Contingency management increased membership in clusters with lower levels of drug use and fewer symptoms of substance use disorder. CONCLUSIONS: Cluster analysis provides person-level output that is more interpretable and actionable than traditional outcome measures, providing a concrete answer to the question of what clinicians can tell patients about the success rates of new treatments.

Stress, craving and mood as predictors of early dropout from opioid agonist therapy.

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.

The chippers, the quitters, and the highly symptomatic: A 12-month longitudinal study of DSM-5 opioid- and cocaine-use problems in a community sample.

BACKGROUND: Individual trajectories of drug use and drug-related problems are highly heterogeneous. There is no standard taxonomy of these trajectories, but one could be developed by defining natural categories based on changes in symptoms of substance-use disorders over time. METHODS: Our study was conducted in a community sample in Baltimore, Maryland. At baseline, all participants were using opioids and/or cocaine, but none were in treatment. Drug use and symptomatology were assessed again at 12 months (N = 115). RESULTS: We defined Quitters as participants who had not used for at least 30 days at follow-up (17%). For the remaining participants, we performed longitudinal cluster analysis on DSM symptom-counts, identifying three trajectory clusters: newly or persistently Symptomatic (40%) participants, Chippers (21.5%) with few symptoms, and Converted Chippers (21.5%) with improved symptom counts. Logistic regression showed that profiles of Quitters did not resemble Chippers, but instead resembled Symptomatic participants, having high probability of disorderly home neighborhood, nonwhite race, and negative mood. Quitters tended to have two protective factors: initiating opioid-agonist treatment during the study (reffect = 0.25, CL95 0.02-0.48) and lack of polydrug use (reffect = 0.25, CL95 0.004-0.49). Converted Chippers tended to be white, with orderly home neighborhoods and less negative mood (reffects 0.24 to 0.31, CL95 0.01-0.54). CONCLUSIONS: Changes in DSM symptomology provided a meaningful measure of individual trajectories. Quitters shared psychosocial characteristics with Symptomatic participants, but not with participants who continued to use with few symptoms. This suggests that Quitters abstained out of necessity, not because their problems were less severe.