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.

Responses to a "Typical" Morning Dose of Kratom in People Who Use Kratom Regularly: A Direct-Observation Study.

INTRODUCTION: Use of kratom has outpaced systematic study of its effects, with most studies reliant on retrospective self-report. METHODS: We aimed to assess acute effects following kratom use in adults who use regularly, and quantify alkaloids in the products, urine, and plasma. Between July and November 2022, 10 adults came to our clinic and orally self-administered their typical kratom dose; blinding procedures were not used. Physiological measures included blood pressure, respiratory rate, heart rate, pulse oximetry, temperature, and pupil diameter. Subjective outcomes included Subjective Opioid Withdrawal Scale, Addiction Research Center Inventory, and Drug Effects Questionnaire. Psychomotor performance was also assessed. RESULTS: Participants were 6 men and 4 women, mean age 41.2 years. Nine were non-Hispanic White; 1 was biracial. They had used kratom for 6.6 years (SD, 3.8 years) on average (2.0-14.1). Sessions were 190.89 minutes on average (SD, 15.10 minutes). Mean session dose was 5.16 g (median, 4.38 g; range, 1.1-10.9 g) leaf powder. Relative to baseline, physiological changes were minor. However, pupil diameter decreased (right, b = -0.70, P < 0.01; left, b = -0.73, P < 0.01) 40-80 minutes postdose and remained below baseline >160 minutes. Subjective Opioid Withdrawal Scale pre-dosing was mild (5.5 ± 3.3) and decreased postdose (b = [-4.0, -2.9], P < 0.01). Drug Effects Questionnaire "feeling effects" increased to 40/100 (SD, 30.5) within 40 minutes and remained above baseline 80 to 120 minutes (b = 19.0, P = 0.04), peaking at 72.7/100; 6 participants rated euphoria as mild on the Addiction Research Center Inventory Morphine-Benzedrine-scale. Psychomotor performance did not reliably improve or deteriorate postdosing. CONCLUSIONS: Among regular consumers, we found few clinically significant differences pre- and post-kratom dosing. Alkaloidal contents in products were within expected ranges.

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.

The Opioid Overdose Resuscitation Education for Addiction Counselors and Trainees (Opioid Overdose REACT) naloxone response education pilot project improved confidence and knowledge among addiction counselors and trainees.

INTRODUCTION: Community programs to teach nonmedical laypeople how to recognize an opioid overdose and effectively resuscitate the victim using naloxone have proliferated recently as a significant component of harm-reduction efforts. Although many such programs target laypeople like first responders or friends and family members of people who use drugs, there are currently no programs that specifically target addiction counselors, despite their work with a client population at high risk of an opioid overdose. METHODS: The four-hour curriculum designed by the authors covered opioid agonist and antagonist pharmacology; opioid toxidrome signs; legal implications and indications for using the naloxone kits; and hands-on training. Participants were two cohorts of addiction counselors and addiction counseling trainees at our institution and an affiliated Opioid Treatment Program methadone clinic. Surveys testing participant knowledge and confidence were conducted at baseline, immediately post-training, six months post-training, and 12 months post-training. RESULTS: Overall, opioid and naloxone pharmacology knowledge, as well as the confidence to intervene in an overdose emergency, improved among participants in both cohorts. Knowledge scores at baseline (n = 36, median 5/10) improved significantly immediately post-training (n = 31, median 7/10, P < 0.0001, Wilcoxon signed-rank test) and were sustained six (n = 19) and 12 months (n = 11) later. Two participants reported using their naloxone kits to successfully reverse a client overdose in the 12 months after taking the course. DISCUSSION: These results from our knowledge translation pilot project suggest that our educational program to train addiction counselors in opioid pharmacology and toxicology, allowing them to recognize and respond to an opioid overdose, is feasible and could be effective. Specific barriers to implementing such educational programs include cost, stigma, and unclear best practice for designing and conducting these programs. CONCLUSIONS: Further study of providing opioid pharmacology education and overdose and naloxone training to addiction counselors and counseling trainees appears to be warranted.

Overdose mortality rates for opioids and stimulant drugs are substantially higher in men than in women: state-level analysis.

Drug overdoses from opioids and stimulants are a major cause of mortality in the United States. It is unclear if there are stable sex differences in overdose mortality for these drugs across states, whether these differ across the lifespan, and if so, whether they can be accounted for by different levels of drug misuse. This was a state-level analysis of epidemiological data on overdose mortality, across 10-year age bins (age range: 15-74), using the CDC WONDER platform for decedents in the United States in 2020-1. The outcome measure was rate of overdose death (per 100,000) for: synthetic opioids (e.g., fentanyl), heroin, psychostimulants with potential for misuse (e.g., methamphetamine), and cocaine. Multiple linear regressions controlled for ethnic-cultural background, household net worth, and sex-specific rate of misuse (from NSDUH, 2018-9). For all these drug categories, males had greater overall overdose mortality than females, after controlling for rates of drug misuse. The mean male/female sex ratio of mortality rate was relatively stable across jurisdictions: synthetic opioids (2.5 [95% CI, 2.4-7]), heroin, (2.9 [95% CI, 2.7-3.1], psychostimulants (2.4 [95% CI, 2.3-5]), and cocaine (2.8 [95% CI, 2.6-9]). With data stratified in 10-year age bins, the sex difference generally survived adjustment (especially in the 25-64 age range). Results indicate that males are significantly more vulnerable than females to overdose deaths caused by opioid and stimulant drugs, taking into account differing state-level environmental conditions and drug misuse levels. These results call for research into diverse biological, behavioral, and social factors that underlie sex differences in human vulnerability to drug overdose.

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.

Examining the paradoxical effects of kratom: a narrative inquiry.

Introduction: 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. Method: 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 (n = 10). Results: 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. Discussion: 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.

Effectiveness of Conditioned Open-label Placebo With Methadone in Treatment of Opioid Use Disorder: A Randomized Clinical Trial.

Importance: Methadone treatment is the most effective evidence-based treatment for opioid use disorder (OUD), but challenges related to dosing and premature treatment dropout argue for adjunct interventions to improve outcomes. One potential behavioral intervention with low risk involves harnessing placebo effects. Objective: To determine the effect of a pharmacologically conditioned open-label placebo (C-OLP) on 90-day methadone dose, retention, drug use, withdrawal, craving, quality of life, and sleep. Design, Setting, and Participants: This 2-arm, open-label, single-blind randomized clinical trial was conducted between December 5, 2017, and August 2, 2019, in an academically affiliated community opioid treatment program. Analyses were conducted between October 1, 2019, and April 30, 2020. A total of 320 newly enrolled adults seeking treatment for moderate to severe OUD were assessed for study eligibility; 131 met eligibility criteria, provided informed consent, and were randomized to either C-OLP or treatment as usual (TAU) in an unequal-block (3:2) manner. Exclusion criteria were pregnancy, hospital/program transfers, and court-ordered treatment. Interventions: Participants randomized to C-OLP received pharmacologic conditioning and a placebo pill and methadone, and participants randomized to TAU were given methadone only. Participants met with the study team 5 times: at baseline (treatment intake) and 2, 4, 8, and 12 weeks postbaseline. Interactions were balanced between the 2 groups. Main Outcomes and Measures: Outcomes included 90-day methadone dose (primary) and treatment retention, drug use, withdrawal, craving, quality of life, and sleep quality (secondary). Analyses were conducted as intention-to-treat. Results: Of the 131 people enrolled in the study, 54 were randomized to TAU and 77 to C-OLP. Mean (SD) age was 45.9 (11.2) years; most of the participants were Black or African American (83 [63.4%]) and male (84 [64.1%]). No significant group differences were observed in the mean (SD) 90-day methadone dose (83.1 [25.1] mg for group TAU, 79.4 [19.6] mg for group C-OLP; t = 0.621991; P = .43), but the groups differed significantly in their retention rates: 33 (61.1%) for TAU and 60 (77.9%) for C-OLP (χ21 = 4.356; P = .04; number needed to treat for the beneficial outcome of 3-month treatment retention, 6; 95% CI, 4-119). C-OLP participants also reported significantly better sleep quality. Conclusions and Relevance: In this randomized clinical trial, C-OLP had no effect on the primary outcome of 90-day methadone dose. However, C-OLP participants were significantly more likely to remain in treatment. These findings support the use of C-OLP as a methadone treatment adjunct, but larger trials are needed to further examine the use of C-OLP. Trial Registration: ClinicalTrials.gov Identifier: NCT02941809.

Overdose mortality rates for opioids or stimulants are higher in males than females, controlling for rates of drug misuse: State-level data.

Importance: Drug overdoses from opioids like fentanyl and heroin and stimulant drugs such as methamphetamine and cocaine are a major cause of mortality in the United States, with potential sex differences across the lifespan. Objective: To determine overdose mortality for specific drug categories across the lifespan of males and females, using a nationally representative state-level sample. Design: State-level analyses of nationally representative epidemiological data on overdose mortality for specific drug categories, across 10-year age bins (age range: 15-74). Setting: Population-based study of Multiple Cause of Death 2020-2021 data from the Centers of Disease Control and Prevention (CDC WONDER platform). Participants: Decedents in the United States in 2020-2021. Main outcome measures: The main outcome measure was sex-specific rates of overdose death (per 100,000) for: synthetic opioids excluding methadone (ICD-10 code: T40.4; predominantly fentanyl), heroin (T40.1), psychostimulants with potential for misuse, excluding cocaine (T43.6, predominantly methamphetamine; labeled "psychostimulants" hereafter), and cocaine (T40.5). Multiple regression analyses were used to control for ethnic-cultural background, household net worth, and sex-specific rate of misuse of the relevant substances (from the National Survey on Drug Use and Health, 2018-2019). Results: For each of the drug categories assessed, males had greater overall overdose mortality than females, after controlling for rates of drug misuse. The mean male/female sex ratio of mortality rate for the separate drug categories was relatively stable across jurisdictions: synthetic opioids (2.5 [95%CI, 2.4-2.7]), heroin, (2.9 [95%CI, 2.7-3.1], psychostimulants (2.4 [95%CI, 2.3-2.5]), and cocaine (2.8 [95%CI, 2.6-2.9]). With data stratified in 10-year age bins, the sex difference generally survived adjustment for state-level ethnic-cultural and economic variables, and for sex-specific misuse of each drug type (especially for bins in the 25-64 age range). For synthetic opioids, the sex difference survived adjustment across the lifespan (i.e., 10-year age bins ranging from 15-74), including adolescence, adulthood and late adulthood. Conclusions and Relevance: The robustly greater overdose mortality in males versus females for synthetic opioids (predominantly fentanyl), heroin, and stimulant drugs including methamphetamine and cocaine indicate that males who misuse these drugs are significantly more vulnerable to overdose deaths. These results call for research into diverse biological, behavioral, and social factors that underlie sex differences in human vulnerability to drug overdose.

Kava (Piper methysticum) in the United States: the quiet rise of a substance with often subtle effects.

Background: Piper methysticum, commonly called kava, has long been consumed in beverage form in the Pacific Islands. Kava use in the US has slowly increased since the 1990s, but is not assessed in major epidemiological surveys.Objectives: To analyze social-media posts about kava from current, past, and prospective users, for motivations, patterns of co-use, and effects.Methods: Text from Reddit posts, and accompanying metadata, were collected and thematically coded by two independent raters.Results: 423 posts were collected, spanning January 2006 through December 2021. Of the 1,211 thematic codes applied, 1,098 (90. 7%) were concordant. Motivations for use bifurcated into self-treatment (for psychiatric or physical health conditions) and recreation; these were not mutually exclusive. Kava was rarely considered strongly euphoriant, but was valued as an anxiolytic. Kava was frequently used with other substances, most commonly kratom. Kava was used at lower doses for self-treatment than for other purposes (pseudo-R2 = 0.11). Undesirable effects (gastrointestinal upset, fatigue) were mentioned, though less often than benefits. Hepatotoxicity, reported elsewhere as a rare, non-dose-related risk, was disputed on the basis of its not having been experienced by those posting.Conclusion: Kava appears to be conceptualized among Reddit posters as an anxiolytic with few risks or adverse effects. As it grows in popularity, especially among people who use other drugs that are more liable to misuse or addiction, it should be assessed in probability samples (i.e. in the major national drug surveys) and clinical practice for its risks, potential benefits, and possible drug-drug interactions.

Using Machine Learning to Predict Treatment Adherence in Patients on Medication for Opioid Use Disorder.

OBJECTIVE: Patients receiving medication for opioid use disorder (MOUD) may continue using nonprescribed drugs or have trouble with medication adherence, and it is difficult to predict which patients will continue to do so. In this study, we develop and validate an automated risk-modeling framework to predict opioid abstinence and medication adherence at a patient's next attended appointment and evaluate the predictive performance of machine-learning algorithms versus logistic regression. METHODS: Urine drug screen and attendance records from 40,005 appointments drawn from 2742 patients at a multilocation office-based MOUD program were used to train logistic regression, logistic ridge regression, and XGBoost models to predict a composite indicator of treatment adherence (opioid-negative and norbuprenorphine-positive urine, no evidence of urine adulteration) at next attended appointment. RESULTS: The XGBoost model had similar accuracy and discriminative ability (accuracy, 88%; area under the receiver operating curve, 0.87) to the two logistic regression models (accuracy, 88%; area under the receiver operating curve, 0.87). The XGBoost model had nearly perfect calibration in independent validation data; the logistic and ridge regression models slightly overestimated adherence likelihood. Historical treatment adherence, attendance rate, and fentanyl-positive urine at current appointment were the strongest contributors to treatment adherence at next attended appointment. DISCUSSION: There is a need for risk prediction tools to improve delivery of MOUD. This study presents an automated and portable risk-modeling framework to predict treatment adherence at each patient's next attended appointment. The XGBoost algorithm appears to provide similar classification accuracy to logistic regression models; however, XGBoost may offer improved calibration of risk estimates compared with logistic regression.

The Protective Effect of Social Reward on Opioid and Psychostimulant Reward and Relapse: Behavior, Pharmacology, and Brain Regions.

Until recently, most modern neuroscience research on addiction using animal models did not incorporate manipulations of social factors. Social factors play a critical role in human addiction: social isolation and exclusion can promote drug use and relapse, while social connections and inclusion tend to be protective. Here, we discuss the state of the literature on social factors in animal models of opioid and psychostimulant preference, self-administration, and relapse. We first summarize results from rodent studies on behavioral, pharmacological, and circuit mechanisms of the protective effect of traditional experimenter-controlled social interaction procedures on opioid and psychostimulant conditioned place preference, self-administration, and relapse. Next, we summarize behavioral and brain-mechanism results from studies using newer operant social-interaction procedures that inhibit opioid and psychostimulant self-administration and relapse. We conclude by discussing how the reviewed studies point to future directions for the addiction field and other neuroscience and psychiatric fields, and their implications for mechanistic understanding of addiction and development of new treatments.SIGNIFICANCE STATEMENT In this review, we propose that incorporating social factors into modern neuroscience research on addiction could improve mechanistic accounts of addiction and help close gaps in translating discovery to treatment. We first summarize rodent studies on behavioral, pharmacological, and circuit mechanisms of the protective effect of both traditional experimenter-controlled and newer operant social-interaction procedures. We then discuss potential future directions and clinical implications.

For Better or Worse: Self-reported Changes in Kratom and Other Substance Use as a Result of the COVID-19 Pandemic.

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. Aim: To examine COVID-19-related changes in kratom use and how these changes were experienced, relative to changes in other commonly used substances. Methods: 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. Results: 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. Conclusions: 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.

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).

Effect of TRV130 and methadone on fentanyl-vs.-food choice and somatic withdrawal signs in opioid-dependent and post-opioid-dependent rats.

The high efficacy mu-opioid receptor (MOR) agonist methadone is an effective opioid use disorder (OUD) medication used exclusively in opioid-dependent patients. However, methadone has undesirable effects that limit its clinical efficacy. Intermediate efficacy MOR agonists may treat OUD with fewer undesirable effects. We compared the effects of methadone with the intermediate efficacy MOR agonist TRV130 (oliceridine) on fentanyl-vs.-food choice and somatic withdrawal signs in opioid-dependent and post-opioid-dependent rats. Male rats (n = 20) were trained under a fentanyl-vs.-food choice procedure. Rats were then provided extended fentanyl (3.2 µg/kg/infusion) access (6 p.m.-6 a.m.) for 10 days to produce opioid dependence/withdrawal. Rats were treated with vehicle (n = 7), TRV130 (3.2 mg/kg; n = 8), or methadone (3.2 mg/kg; n = 5) three times per day after each extended-access session (8:30 a.m., 11 a.m., 1:30 p.m.). Withdrawal sign scoring (1:55 p.m.) and choice tests (2-4 p.m.) were conducted daily. Vehicle, TRV130, and methadone effects on fentanyl choice were redetermined in post-opioid-dependent rats. Vehicle-, TRV130-, and methadone-treated rats had similar fentanyl intakes during extended access. Vehicle-treated rats exhibited increased withdrawal signs and decreased bodyweights. Both methadone and TRV130 decreased these withdrawal signs. TRV130 was less effective than methadone to decrease fentanyl choice and increase food choice in opioid-dependent rats. Neither methadone nor TRV130 decreased fentanyl choice in post-opioid-dependent rats. Results suggest that higher MOR activation is required to reduce fentanyl choice than withdrawal signs in fentanyl-dependent rats. Additionally, given that TRV130 did not precipitate withdrawal in opioid-dependent rats, intermediate efficacy MOR agonists like TRV130 may facilitate the transition of patients with OUD from methadone to lower efficacy treatments like buprenorphine.

Need for clarity and context in case reports on kratom use, assessment, and intervention.

This Letter to the Editor is a response to Broyan and colleagues who recently published a Case Report presenting data on 28 patients in the United States who identified kratom as their primary substance of use and who were subsequently induced on buprenorphine/naloxone for a reported diagnosis of kratom use disorder. We applaud the authors for helping to advance the science on kratom and recognize the difficulties in conducting kratom-related clinical assessment and research. However, a number of inconsistences and generalizations were identified in this Case Report, which also lacked some critical context. Importantly, such inconsistencies and generalizations can be observed throughout kratom-specific case reports. We feel this is now an important opportunity to highlight these issues that are present in the Broyan and colleagues Case report but emphasize that they are not unique to it. We do this with the hope that by acknowledging these issues it can help inform editors, clinicians, and researchers who may not be familiar with kratom and, as a result of this unfamiliarity, may inadvertently present findings in a manner that could confuse readers and even misinform clinical researchers and practitioners.

Kratom use as more than a "self-treatment".

Background: Mitragyna speciosa (kratom) is increasingly used in the United States for its pharmacological effects. Kratom's relative novelty makes for a dynamic situation, such that use motivations are not firmly established and may be changing. Investigators and clinicians require frequent updates on kratom trends.Objectives: To assess the current state of kratom-use initiation, sourcing, motivations, preference, conceptualizations, and perceived stigma, using survey responses from current and former users.Methods: Between April-May 2021 we recontacted 289 respondents who reported lifetime kratom use (on an unrelated survey) to answer kratom-specific questions.Results: The sample (N=129) was majority female (51.9%) and white (71.9%). Most (69.0%) reported first trying kratom after 2015. Mean age of use initiation (29.9 years) was older than for other substances, including opioids. Kratom ranked as a preferred substance by 48.5%. The strongest drug association with past-year kratom use was vaped nicotine (OR=3.31,95% CI 1.23-8.88). Use was less likely among those prescribed buprenorphine in the past year (OR=0.03, CI 0.01-0.28). Past-month cannabis use (OR=4.18,CI 1.80-9.72) had the strongest association with past-month kratom use. Over 40 use motivations were endorsed, many (but not all) supporting the "self-treatment" narrative of kratom use, including use as an opioid, alcohol, or stimulant substitute. Treatment shortfalls were associated with decisions to try kratom.Conclusions: Kratom use motivations are diversifying, with multiple factors driving use. As sales continue to increase, the public-health, clinical, and policy responses to kratom should be grounded in rigorous bench-to-bedside scientific research. Comprehensive study of kratom is currently lacking.