Real-world Assessment, Prediction, and Treatment Section – Publications

@article{pmid40839514,

title = {Is bedtime use of kratom (Mitragyna speciosa) a sleep aid or disruptor? Examining its daily effects and individual differences},

author = {Chung Jung Mun and Patricia Timmons and Leigh V Panlilio and Christopher D Verrico and Ynhi T Thomas and C Austin Zamarripa and David H Epstein and Kirsten E Smith},

url = {https://pubmed.ncbi.nlm.nih.gov/40839514/},

doi = {10.1037/pha0000794},

issn = {1936-2293},

year  = {2025},

date = {2025-10-01},

urldate = {2025-10-01},

journal = {Exp Clin Psychopharmacol},

volume = {33},

number = {5},

pages = {513--522},

abstract = {Kratom () is a psychoactive botanical native to Southeast Asia increasingly used in the United States for various self-reported benefits, including sleep improvement. However, empirical evidence concerning kratom's effects on sleep is limited. Here, we examined the association between bedtime kratom use and self-reported sleep outcomes in naturalistic settings across consecutive days, while also exploring sex and chronic pain status as potential moderators. A secondary analysis was conducted using the data from a 15-day ecological momentary assessment study of 357 U.S. adults who reported regularly using kratom. Participants made daily reports of their bedtime kratom use and rated their sleep duration and quality. Linear mixed-effects models assessed associations between bedtime kratom use and sleep outcomes, with sex and chronic pain status as moderators, controlling for age. Bedtime kratom use occurred on 23.4% of days and was associated with modest increases in sleep duration (13 min) and perceived quality (5.93-point increase on a 0-100 scale). Female respondents reported greater improvements in sleep quality (but not duration) than male respondents. Participants with chronic pain reported greater improvements in sleep duration and quality compared to those without chronic pain. Bedtime kratom use is associated with modest sleep duration and quality improvements, particularly in adults with chronic pain, and better sleep quality in female respondents. These findings among experienced kratom consumers suggest the need for human laboratory studies in kratom-naïve participants to determine causality and underlying mechanisms, which could help inform clinical guidance and policy as kratom use continues to rise. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40377101,

title = {Chemical Analysis and Alkaloid Intake for Kratom Products Available in the United States},

author = {Abhisheak Sharma and Kirsten E Smith and Michelle A Kuntz and Erin C Berthold and Omar I Elashkar and Nicholas Guadagnoli and Siva Rama Raju Kanumuri and Sushobhan Mukhopadhyay and Leigh V Panlilio and David H Epstein and Christopher R McCurdy},

url = {https://pubmed.ncbi.nlm.nih.gov/40377101/},

doi = {10.1002/dta.3906},

issn = {1942-7611},

year  = {2025},

date = {2025-10-01},

urldate = {2025-10-01},

journal = {Drug Test Anal},

volume = {17},

number = {10},

pages = {1974--1984},

abstract = {Previously, we used ecological momentary assessment (EMA) to evaluate motivations and temporal patterns of kratom use for 15 days among US adult kratom consumers (N = 357). Here we present the content analyses of the products used during that nationwide study, with quantification of 10 kratom alkaloids. The samples (N = 341) were primarily whole-leaf products, not extracts, and were similar to each other in their alkaloid composition, closely matching the chromatographic-mass spectrometry fingerprint expected for Mitragyna speciosa leaf material. We found no evidence of adulteration with illicit or prescription drugs. With participants' self-reported data on kratom amount per use, we calculated mitragynine intake per use: mean 31.3 mg and median 25.4 mg (range 2.0-205.9 mg). With self-reported data on frequency, we calculated mitragynine intake per day, it ranged from 78.3 to 134.6 mg (mean) or 50.8 to 101.6 mg (median). This is the most comprehensive analysis of US whole-leaf kratom products to date. The coupling of self-report and product sample-analysis data to quantify daily alkaloid intake is foundational for designing controlled clinical trials of kratom in healthy volunteers. These findings on kratom products' chemical composition and daily kratom alkaloid consumption can also inform clinicians, policymakers, and consumers, particularly for whole-leaf material.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39883932,

title = {At least four groups of kratom consumers in the United States: latent-class analysis of motivations for kratom use},

author = {Katherine Hill and Jeffrey M Rogers and Oliver Grundmann and David H Epstein and Kirsten E Smith},

url = {https://pubmed.ncbi.nlm.nih.gov/39883932/},

doi = {10.1080/00952990.2024.2414319},

issn = {1097-9891},

year  = {2025},

date = {2025-03-01},

urldate = {2025-03-01},

journal = {Am J Drug Alcohol Abuse},

volume = {51},

number = {2},

pages = {191--203},

abstract = { Kratom is a plant with alkaloids acting at opioid, serotonergic, adrenergic, and other receptors. Consumers report numerous use motivations. To distinguish subgroups of kratom consumers by kratom-use motivations using latent-class analysis. From July to November 2022, we utilized convenience sampling and surveyed regular kratom consumers ( = 395, 38.1 years (SD 11.2), 54.9% male, 81.3% White) regarding demographics, lifetime and past-year substance use and preferences, substance use disorder history, healthcare barriers, kratom-use motivations, and general health. We used latent-class analysis to identify subgroups by use motivation and calculated conditional probabilities (P) for variables in each class. A four-class model best fit our data. The largest class (32.4%) was characterized by the use of kratom for self-treatment of chronic pain (P = .91). The smallest class (19.2%) also reported using kratom for self-treatment, but usually as a long-term replacement for other substances (P = .75). The other two classes (24.8% and 23.5%) reported using kratom for management of anxiety (P = .87-.95) and depressive symptoms (P = .61-.89) and for recreation (P = .56- .86). These were distinguished from one another by probability of at least moderate kratom use disorder (P = .17 vs. .53), with greater probability observed in the class with greater anxiety (P = .13 vs. .50) and depressive (P = .34 vs. .82) symptom severity and more likely recreational use motivation (P = .56 vs. .86). Kratom consumers can be classified by their use motivations. As with other psychoactive substances, the range of motivations is consistent with the range of likely effects. It is not yet clear whether some motivations might indicate the risk of problems.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39505119,

title = {Kratom (Mitragyna speciosa) use for self-management of pain: Insights from cross-sectional and ecological momentary assessment data},

author = {Chung Jung Mun and Leigh V Panlilio and Kelly E Dunn and Johannes Thrul and Christopher R McCurdy and David H Epstein and Kirsten E Smith},

url = {https://pubmed.ncbi.nlm.nih.gov/39505119/},

doi = {10.1016/j.jpain.2024.104726},

issn = {1528-8447},

year  = {2025},

date = {2025-01-01},

urldate = {2025-01-01},

journal = {J Pain},

volume = {26},

pages = {104726},

abstract = {Kratom (Mitragyna speciosa) is increasingly used in the US for self-management of pain, despite limited research on its efficacy and safety. To better understand how and why people use kratom for pain self-management, we analyzed baseline survey data (N = 395) and 15-day ecological momentary assessment (EMA) data (N = 357) from kratom consumers across the US. Although we recruited participants based on their kratom use, not on whether they used it for pain management, nearly half (49.1 %) met criteria for chronic pain, with many reporting substantial pain relief and high effectiveness of kratom in managing pain. A majority (69.2 %) reported difficulties in obtaining adequate pain treatment, and most indicated that these challenges impacted their decision to try kratom. Most participants did not report concerns about overuse or significant side effects. EMA data showed that, regardless of chronic-pain status, pain relief was the most frequently endorsed primary motivation for daily kratom use. There were no significant association between daily pain levels and kratom use frequency, and no difference in the daily kratom use between those with vs. without chronic pain. Recent kratom use was associated with lower current pain levels. Stronger subjective effects of kratom were associated with lower pain levels. This effect was significantly moderated by chronic-pain status: those with chronic pain showed a stronger link between subjective kratom effects and pain reduction. These findings underscore the urgent need for systematic, rigorous research on long-term implications, efficacy, and safety of kratom in pain management to guide informed clinical practices and regulatory policies. PERSPECTIVE: This study reveals that chronic pain is common among kratom consumers, who frequently use it for pain self-management and report significant relief, as shown by ecological momentary assessment. There is an urgent need for research into kratom's safety, efficacy, and mechanisms to guide clinical practice and inform policies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{articled,

title = {Latent Classes of Adverse Childhood Experiences (ACEs) and Adult Substance-use Problems and Psychosocial Outcomes: Complex and Heterogeneous Associations},

author = {Emily Herberholz and Rachel Wolchok and Jeffrey Rogers and Sophia Selenou-Yemgang and Bianca Beckwith and Kirsten Smith and David Epstein},

doi = {10.1007/s11469-025-01527-w},

year  = {2025},

date = {2025-01-01},

urldate = {2025-01-01},

journal = {International Journal of Mental Health and Addiction},

pages = {1-20},

abstract = {Adverse childhood experiences (ACEs), expressed as summary scores, are associated with adverse adult outcomes. We aimed to detect more nuanced associations via latent class analysis (LCA) of ACEs. We tested associations between class membership and adult anxiety, depression, loneliness, stress, and substance-use patterns/disorders. Our nationwide data set, part of our larger study of substance use with or without addiction, included 2615 mTurk workers with any past-6-month alcohol use (71.6% n = 986) or any past-6-month nonmedical use of opioids or stimulants (28.4%, n = 391). Using a 10-item ACE questionnaire, we identified high, moderate, and two differentiable low-ACE classes (exposed to either parental substance use or divorce). In regression models, the high-ACE class had more past-year substance use (ORs 2.01–3.38, R² = 0.12), problematic use (ORs 1.89–2.66, R² = 0.10), SUD treatment (ORs 2.10–5.45, R² = 0.15), and psychological symptoms (betas 1.32–8.74, R² = 0.11–0.19). Despite aggregate associations, the low R² values underscore within-class heterogeneity in outcomes. ACE patterns are informative about adult outcomes in the aggregate, but do not support case-by-case inferences.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39134892,

title = {Controversies in Assessment, Diagnosis, and Treatment of Kratom Use Disorder},

author = {Kirsten E Smith and David H Epstein and Stephanie T Weiss},

url = {https://pubmed.ncbi.nlm.nih.gov/39134892/},

doi = {10.1007/s11920-024-01524-1},

issn = {1535-1645},

year  = {2024},

date = {2024-09-01},

urldate = {2024-09-01},

journal = {Curr Psychiatry Rep},

volume = {26},

number = {9},

pages = {487--496},

abstract = {PURPOSE OF REVIEW: We apply the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria for substance use disorders (SUDs) to the herbal product kratom. Similarities and differences between kratom use disorder (KUD) and other SUDs are explored, along with assessment, diagnostic, and therapeutic recommendations for KUD.nnRECENT FINDINGS: Literature reports of "kratom addiction" or KUD rarely specify the criteria by which patients were diagnosed. Individuals meeting DSM-5 KUD criteria typically do so via tolerance and withdrawal, using more than intended, and craving, not functional or ​psychosocial disruption, which occur rarely. Most clinicians who use medication to treat patients with isolated KUD select buprenorphine formulations, although there are no controlled studies showing that buprenorphine is safe or efficacious in this patient population. Diagnosis and treatment decisions for KUD should be systematic. We propose an algorithm that takes into consideration whether KUD occurs with comorbid opioid use disorder.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38277146,

title = {Ecological Momentary Assessment of Self-Reported Kratom Use, Effects, and Motivations Among US Adults},

author = {Kirsten E Smith and Leigh V Panlilio and Jeffrey D Feldman and Oliver Grundmann and Kelly E Dunn and Christopher R McCurdy and Albert Garcia-Romeu and David H Epstein},

url = {https://pubmed.ncbi.nlm.nih.gov/38277146/},

doi = {10.1001/jamanetworkopen.2023.53401},

issn = {2574-3805},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {JAMA Netw Open},

volume = {7},

number = {1},

pages = {e2353401},

abstract = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37213182,

title = {Novel methods for the remote investigation of emerging substances: Application to kratom},

author = {Kirsten E Smith and Jeffrey D Feldman and Kelly E Dunn and Christopher R McCurdy and Oliver Grundmann and Albert Garcia-Romeu and Leigh V Panlilio and Jeffrey M Rogers and Abhisheak Sharma and Salma Pont-Fernandez and Marina Kheyfets and David H Epstein},

url = {https://pubmed.ncbi.nlm.nih.gov/37213182/},

doi = {10.1037/pha0000656},

issn = {1936-2293},

year  = {2023},

date = {2023-05-01},

urldate = {2023-05-01},

journal = {Exp Clin Psychopharmacol},

abstract = {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) 2023 APA, all rights reserved).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Smith:2023aa,

title = {Diagnostic Ambiguities and Underuse of Clinical Assessment Tools: A Systematic Review of Case Reports on Kratom Addiction and Physical Dependence},

author = {Kirsten E. Smith and Jeffrey D. Feldman and Destiny Schriefer and Stephanie T. Weiss and Oliver Grundmann and Kelly E. Dunn and Darshan Singh and Christopher R. McCurdy and Gisela Butera and David H. Epstein},

url = {https://doi.org/10.1007/s40429-023-00474-7},

doi = {10.1007/s40429-023-00474-7},

isbn = {2196-2952},

year  = {2023},

date = {2023-03-13},

urldate = {3023-03-13},

journal = {Current Addiction Reports},

volume = {10},

number = {2},

pages = {282–292},

abstract = {This systematic review examines case reports of kratom physical dependence or addiction, focusing on assessment, diagnosis, and treatment methods and the completeness of the clinical data presented.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37214465,

title = {Examining the paradoxical effects of kratom: a narrative inquiry},

author = {Kirsten E Smith and Jeffrey D Feldman and Kelly E Dunn and Christopher R McCurdy and Stephanie T Weiss and Oliver Grundmann and Albert Garcia-Romeu and Janeen Nichels and David H Epstein},

url = {https://pubmed.ncbi.nlm.nih.gov/37214465/},

doi = {10.3389/fphar.2023.1174139},

issn = {1663-9812},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Front Pharmacol},

volume = {14},

pages = {1174139},

abstract = { Surveys and case reports have documented kratom use in the United States (US) for over a decade. However, those reports have generally not examined in depth the role kratom plays in the lives of those who use it regularly for sustained periods. Until there are controlled studies of the pharmacology and subjective effects of kratom alkaloids in humans, one of the best sources of insight on kratom-product use remains qualitative data with nuanced descriptions of kratom effects from those who use it regularly.  We conducted semistructured qualitative interviews with adults who regularly use kratom products, as part of a laboratory study of kratom-product self-administration. This qualitative component of the study was conducted as a narrative case-report series ( = 10).  Despite some differences among participants, all experienced acute combination effects that were largely, even simultaneously, analgesic and stimulatory. Most participants had decreased their dosages over time, and one planned to quit. Five of the 10 participants met DSM-5-based criteria for kratom-use disorder (3 mild, 1 moderate, 1 severe, by symptoms counts). When kratom was inadvertently taken in larger than intended doses, participants described a constellation of symptoms that they called "the wobbles" (a jittery feeling accompanied by what seemed to be nystagmus); this was rare, but could be of scientific and clinical interest as a possible manifestation of serotonin syndrome. Most participants described tolerance but considered kratom generally safe at low-moderate doses, providing perceived benefits with less potential risk for adverse effects compared to pharmaceuticals or illicit drugs.  In-depth interview data like these help confirm and clarify findings from larger survey studies and clinician-driven case reports. They are needed to inform the policy practice regarding kratom and may also help inform future experimental designs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35220331,

title = {Assessment of Kratom Use Disorder and Withdrawal Among an Online Convenience Sample of US Adults},

author = {Kirsten E Smith and Kelly E Dunn and Jeffrey M Rogers and Albert Garcia-Romeu and Justin C Strickland and David H Epstein},

url = {https://pubmed.ncbi.nlm.nih.gov/35220331/},

doi = {10.1097/ADM.0000000000000986},

issn = {1935-3227},

year  = {2022},

date = {2022-11-01},

journal = {J Addict Med},

volume = {16},

number = {6},

pages = {666--670},

abstract = {INTRODUCTION: Since 2007, kratom use in the United States has increased, centered around nonmedical self-treatment of pain, psychiatric, and substance use disorder symptoms. Reports of kratom withdrawal have emerged amidst description of therapeutic effects, yet we know little about disordered use. Our objective was to assess Diagnostic and Statistical Manual-5 substance use disorder for kratom ("kratom use disorder," KUD) and examine kratom withdrawal symptoms among those who ever used regularly. We also sought to identify clinical characteristics of respondents who qualified for current, remitted, or never KUD.nnMETHODS: Between April and May 2021, we re-recruited online respondents who reported lifetime kratom use on an unrelated survey into our cross-sectional kratom survey study, permitting a diverse sample of current and former kratom-using persons.nnRESULTS: A total of 129/289 (44.6%) evaluable surveys were obtained. Over half (52.7%) of respondents never met KUD diagnostic criteria; 17.8% were assessed remitted, and 29.5% met current (past-year) KUD threshold. For past-year KUD, severity was: 14.0% mild, 7.0% moderate, and 8.5% severe. Pain, psychiatric symptoms, and polydrug use were found across all groups. KUD symptoms reflected increased use, tolerance, withdrawal, unsuccessful quit attempts, and craving; 9.3% reported decreases in important social, occupational, or recreational activities because of use. Withdrawal symptoms were moderate and included gastrointestinal upset, restlessness, anxiety, irritability, fatigue/low energy, and craving.nnCONCLUSIONS: As assessed here, tolerance and withdrawal are primary KUD features rather than psychosocial impairments. As kratomis often used among persons with a myriad of health conditions, clinicians should be aware of and assess for kratom use and withdrawal.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35980695,

title = {Variability in intensively assessed mood: Systematic sources and factor structure in outpatients with opioid use disorder},

author = {Samuel W Stull and Jacqueline Mogle and Jeremiah W Bertz and Albert J Burgess-Hull and Leigh V Panlilio and Stephanie T Lanza and Kenzie L Preston and David H Epstein},

url = {https://pubmed.ncbi.nlm.nih.gov/35980695/},

doi = {10.1037/pas0001160},

issn = {1939-134X},

year  = {2022},

date = {2022-10-01},

urldate = {2022-10-01},

journal = {Psychol Assess},

volume = {34},

number = {10},

pages = {966--977},

abstract = {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;  = 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).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35217274,

title = {Trajectories of craving during medication-assisted treatment for opioid-use disorder: Subtyping for early identification of higher risk},

author = {Albert J Burgess-Hull and Leigh V Panlilio and Kenzie L Preston and David H Epstein},

url = {https://pubmed.ncbi.nlm.nih.gov/35217274/},

doi = {10.1016/j.drugalcdep.2022.109362},

issn = {1879-0046},

year  = {2022},

date = {2022-04-01},

urldate = {2022-04-01},

journal = {Drug Alcohol Depend},

volume = {233},

pages = {109362},

abstract = {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.nnDESIGN, 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.nnMEASUREMENTS: 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.nnFINDINGS: 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.nnCONCLUSIONS: 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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35156103,

title = {Were self-described introverts "immune" to increased drug use and entrapment during the pandemic?},

author = {Leigh V Panlilio and Anysia Lee and Kirsten E Smith and David H Epstein},

url = {https://pubmed.ncbi.nlm.nih.gov/35156103/},

doi = {10.1016/j.dadr.2022.100024},

issn = {2772-7246},

year  = {2022},

date = {2022-03-01},

urldate = {2022-03-01},

journal = {Drug Alcohol Depend Rep},

volume = {2},

pages = {100024},

abstract = {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.nnMETHODS: 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.nnRESULTS: 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.nnCONCLUSIONS: Satisfactory social activity (even in small amounts) was associated with better outcomes, mostly without regard to introversion.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36199697,

title = {For Better or Worse: Self-reported Changes in Kratom and Other Substance Use as a Result of the COVID-19 Pandemic},

author = {Jeffrey M Rogers and Kirsten E Smith and Destiny Schriefer and David H Epstein},

url = {https://pubmed.ncbi.nlm.nih.gov/36199697/},

doi = {10.1177/11782218221123977},

issn = {1178-2218},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Subst Abuse},

volume = {16},

pages = {11782218221123977},

abstract = {BACKGROUND: Kratom is taken to self-treat pain and symptoms of psychiatric disorders, including substance-use disorders (SUDs) and opioid withdrawal. Before COVID-19, kratom use was increasing in the US, however, there are few published data on whether that trend continued during the COVID-19 pandemic, which could have affected kratom use in multiple ways.nnAIM: To examine COVID-19-related changes in kratom use and how these changes were experienced, relative to changes in other commonly used substances.nnMETHODS: Using Amazon Mechanical Turk, 2615 evaluable surveys were completed between September 2020 and March 2021. Responses from past-month and past-year kratom-using adults (N = 174) indicating changes for the better or worse were examined using generalized linear mixed effects models, and relevant open-text responses (n = 85) were thematically coded.nnRESULTS: For kratom 33% (n = 58) reported a Covid-related increase and 24% (n = 42) reported a Covid-related decrease. Controlling for changes in amount used, alcohol (OR = 5.02), tobacco (OR = 4.72), and nonmedical opioid use (OR = 3.42) were all more likely to have changed for the worse, compared with kratom use. Relative to decreases in kratom use, decreases in alcohol (OR = 3.21) and tobacco (OR = 6.18) use were more likely to be changes for the better. Cannabis use was the only substance to display a probability lower than 50% of being a decrease for the better, and of the increases, cannabis use displayed the highest probability of being for the better.nnCONCLUSIONS: Increases in kratom and cannabis use were less likely than alcohol and tobacco to be reported as changes for the worse, and decreases in kratom and cannabis use were more likely than alcohol and tobacco to be reported as changes for the better. These findings indicate that people differently conceptualize their relationships with kratom and cannabis, compared to their relationships with alcohol and tobacco.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33973924,

title = {Potential Value of the Insights and Lived Experiences of Addiction Researchers With Addiction},

author = {Samuel W Stull and Kirsten E Smith and Noel A Vest and Devin P Effinger and David H Epstein},

url = {https://pubmed.ncbi.nlm.nih.gov/33973924/},

doi = {10.1097/ADM.0000000000000867},

issn = {1935-3227},

year  = {2021},

date = {2021-12-01},

urldate = {2021-03-01},

journal = {J Addict Med},

volume = {16},

number = {2},

pages = {135--137},

abstract = {People in remission from substance use disorders (SUDs) have a history of using their own experience (also referred to as "experiential knowledge" or "expertise") to support those in or seeking SUD remission. In recent years, people with this experiential knowledge are being incorporated into research protocols to better guide research questions and inform the real-world uptake of SUD treatments and recovery supports. In these research contexts, however, those with research expertise and addiction rarely speak freely about these overlapping perspectives. The aim of this commentary is to increase awareness regarding the existence of this group (addiction researchers with addiction) and to explore the possibility that their expertise may help advance addiction science while helping to reduce stigma.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34472889b,

title = {I feel good? Anhedonia might not mean "without pleasure" for people treated for opioid use disorder},

author = {Samuel W Stull and Jeremiah W Bertz and Leigh V Panlilio and William J Kowalczyk and Karran A Phillips and Landhing M Moran and Jia-Ling Lin and Massoud Vahabzadeh and Patrick H Finan and Kenzie L Preston and David H Epstein},

url = {https://pubmed.ncbi.nlm.nih.gov/34472889/},

doi = {10.1037/abn0000674},

issn = {1939-1846},

year  = {2021},

date = {2021-07-01},

urldate = {2021-07-01},

journal = {J Abnorm Psychol},

volume = {130},

number = {5},

pages = {537--549},

abstract = { 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).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33558983,

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

author = {Leigh V Panlilio and Samuel W Stull and Jeremiah W Bertz and Albert J Burgess-Hull and Stephanie T Lanza and Brenda L Curtis and Karran A Phillips and David H Epstein and Kenzie L Preston},

url = {https://pubmed.ncbi.nlm.nih.gov/33558983/},

doi = {10.1007/s00213-021-05782-2},

issn = {1432-2072},

year  = {2021},

date = {2021-06-01},

urldate = {2021-06-01},

journal = {Psychopharmacology (Berl)},

volume = {238},

number = {6},

pages = {1513--1529},

abstract = {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.nnOBJECTIVES 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.nnRESULTS: 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.nnCONCLUSIONS: 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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33425652,

title = {Ambulatory Assessment Methods to Examine Momentary State-Based Predictors of Opioid Use Behaviors},

author = {Albert Burgess-Hull and David H Epstein},

url = {https://pubmed.ncbi.nlm.nih.gov/33425652/},

doi = {10.1007/s40429-020-00351-7},

issn = {2196-2952},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Curr Addict Rep},

volume = {8},

number = {1},

pages = {122--135},

abstract = {PURPOSE OF REVIEW: Addiction scientists have begun using ambulatory assessment methods-including ecological momentary assessment (EMA), experience sampling, and daily diaries-to collect real-time or near-real-time reports of participants' internal states in their natural environments. The goal of this short review is to synthesize EMA findings from our research group, which has studied several hundred outpatients during treatment for opioid-use disorder (OUD). (We cite pertinent findings from other groups, but have not tried to be comprehensive.) One of our main goals in using EMA is to examine momentary changes in internal states that proximally predict, or concurrently mark, events such as lapses to opioid use.nnRECENT FINDINGS: We summarize findings evaluating several classes of momentary markers or predictors (craving, stress, negative and positive moods, and physical pain/discomfort) of lapses and other states/behaviors. Craving and some negatively valenced mood states are concurrently and prospectively associated with lapses to opioid use during treatment. Craving is also concurrently and prospectively associated with momentary changes in stress and mood. Convincing evidence has not yet emerged for stress as a robust redictor of lapse to opioid use; it appears to be contributory, but neither necessary nor sufficient.nnSUMMARY: Ambulatory assessment can capture changes in internal states and drug-related behaviors in situ and at high temporal resolution. We recommend research strategies that may increase the clinical and prognostic utility of ambulatory assessment, including denser sampling (i.e., more assessments per day) and more attention to heterogeneity across people and across populations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33024318,

title = {Improving translation of animal models of addiction and relapse by reverse translation},

author = {Marco Venniro and Matthew L Banks and Markus Heilig and David H Epstein and Yavin Shaham},

url = {https://pubmed.ncbi.nlm.nih.gov/33024318/},

doi = {10.1038/s41583-020-0378-z},

issn = {1471-0048},

year  = {2020},

date = {2020-11-01},

urldate = {2020-11-01},

journal = {Nat Rev Neurosci},

volume = {21},

number = {11},

pages = {625--643},

abstract = {Critical features of human addiction are increasingly being incorporated into complementary animal models, including escalation of drug intake, punished drug seeking and taking, intermittent drug access, choice between drug and non-drug rewards, and assessment of individual differences based on criteria in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Combined with new technologies, these models advanced our understanding of brain mechanisms of drug self-administration and relapse, but these mechanistic gains have not led to improvements in addiction treatment. This problem is not unique to addiction neuroscience, but it is an increasing source of disappointment and calls to regroup. Here we first summarize behavioural and neurobiological results from the animal models mentioned above. We then propose a reverse translational approach, whose goal is to develop models that mimic successful treatments: opioid agonist maintenance, contingency management and the community-reinforcement approach. These reverse-translated 'treatments' may provide an ecologically relevant platform from which to discover new circuits, test new medications and improve translation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32990768,

title = {Beyond abstinence and relapse: cluster analysis of drug-use patterns during treatment as an outcome measure for clinical trials},

author = {Leigh V Panlilio and Samuel W Stull and Jeremiah W Bertz and Albert J Burgess-Hull and William J Kowalczyk and Karran A Phillips and David H Epstein and Kenzie L Preston},

url = {https://pubmed.ncbi.nlm.nih.gov/32990768/},

doi = {10.1007/s00213-020-05618-5},

issn = {1432-2072},

year  = {2020},

date = {2020-11-01},

urldate = {2020-11-01},

journal = {Psychopharmacology (Berl)},

volume = {237},

number = {11},

pages = {3369--3381},

abstract = {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.nnOBJECTIVES: 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.nnMETHODS: 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.nnRESULTS: 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.nnCONCLUSIONS: 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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31969695,

title = {Let's agree to agree: a comment on Hogarth (2020), with a plea for not-so-competing theories of addiction},

author = {David H Epstein},

url = {Let's agree to agree: a comment on Hogarth (2020), with a plea for not-so-competing theories of addiction},

doi = {10.1038/s41386-020-0618-y},

issn = {1740-634X},

year  = {2020},

date = {2020-04-01},

urldate = {2020-04-01},

journal = {Neuropsychopharmacology},

volume = {45},

number = {5},

pages = {715--716},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32195362,

title = {Prediction of stress and drug craving ninety minutes in the future with passively collected GPS data},

author = {David H Epstein and Matthew Tyburski and William J Kowalczyk and Albert J Burgess-Hull and Karran A Phillips and Brenda L Curtis and Kenzie L Preston},

url = {https://pubmed.ncbi.nlm.nih.gov/32195362/},

doi = {10.1038/s41746-020-0234-6},

issn = {2398-6352},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {NPJ Digit Med},

volume = {3},

pages = {26},

abstract = {Just-in-time adaptive interventions (JITAIs), typically smartphone apps, learn to deliver therapeutic content when users need it. The challenge is to "push" content at algorithmically chosen moments without making users trigger it with effortful input. We trained a randomForest algorithm to predict heroin craving, cocaine craving, or stress (reported via smartphone app 3x/day) 90 min into the future, using 16 weeks of field data from 189 outpatients being treated for opioid-use disorder. We used only one form of continuous input (along with person-level demographic data), collected passively: an indicator of environmental exposures along the past 5 h of movement, as assessed by GPS. Our models achieved excellent overall accuracy-as high as 0.93 by the end of 16 weeks of tailoring-but this was driven mostly by correct predictions of absence. For predictions of presence, "believability" (positive predictive value, PPV) usually peaked in the high 0.70s toward the end of the 16 weeks. When the prediction target was more rare, PPV was lower. Our findings complement those of other investigators who use machine learning with more broadly based "digital phenotyping" inputs to predict or detect mental and behavioral events. When target events are comparatively subtle, like stress or drug craving, accurate detection or prediction probably needs effortful input from users, not passive monitoring alone. We discuss ways in which accuracy is difficult to achieve or even assess, and warn that high overall accuracy (including high specificity) can mask the abundance of false alarms that low PPV reveals.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}