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.

Post-stroke Cognition is Associated with Stroke Survivor Quality of Life and Caregiver Outcomes: A Systematic Review and Meta-analysis.

Disability arising from post-stroke cognitive impairment is a likely contributor to the poor quality of life (QoL) stroke survivors and their carers frequently experience, but this has not been summarily quantified. A systematic literature review and meta-analysis was completed examining the association between general and domain-specific post-stroke cognitive functioning and adult stroke survivor QoL, caregiver QoL, and caregiver burden. Five databases were systematically searched, and eligibility for inclusion, data extraction, and study quality were evaluated by two reviewers using a standardised protocol. Effects sizes (r) were estimated using a random effects model. Thirty-eight studies were identified, generating a sample of 7365 stroke survivors (median age 63.02 years, range 25-93) followed for 3 to 132 months post-stroke. Overall cognition (all domains combined) demonstrated a significant small to medium association with QoL, r = 0.23 (95% CI 0.18-0.28), p < 0.001. The cognitive domains of speed, attention, visuospatial, memory, and executive skills, but not language, also demonstrated a significant relationship with QoL. Regarding caregiver outcomes, 15 studies were identified resulting in a sample of 2421 caregivers (median age 58.12 years, range 18-82) followed for 3 to 84 months post-stroke. Stroke survivor overall cognitive ability again demonstrated a significant small to medium association with caregiver outcomes (QoL and burden combined), r = 0.17 (95% CI 0.10-0.24), p < 0.001. In conclusion, lower post-stroke cognitive performance is associated with significant reductions in stroke survivor QoL and poorer caregiver outcomes. Cognitive assessment is recommended early to identify those at risk and implement timely interventions to support both stroke survivors and their caregivers.

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.

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.

Cannabis use may attenuate neurocognitive performance deficits resulting from methamphetamine use disorder.

OBJECTIVE: Methamphetamine and cannabis are two widely used, and frequently co-used, substances with possibly opposing effects on the central nervous system. Evidence of neurocognitive deficits related to use is robust for methamphetamine and mixed for cannabis. Findings regarding their combined use are inconclusive. We aimed to compare neurocognitive performance in people with lifetime cannabis or methamphetamine use disorder diagnoses, or both, relative to people without substance use disorders. METHOD: 423 (71.9% male, aged 44.6 ± 14.2 years) participants, stratified by presence or absence of lifetime methamphetamine (M-/M+) and/or cannabis (C-/C+) DSM-IV abuse/dependence, completed a comprehensive neuropsychological, substance use, and psychiatric assessment. Neurocognitive domain T-scores and impairment rates were examined using multiple linear and binomial regression, respectively, controlling for covariates that may impact cognition. RESULTS: Globally, M+C+ performed worse than M-C- but better than M+C-. M+C+ outperformed M+C- on measures of verbal fluency, information processing speed, learning, memory, and working memory. M-C+ did not display lower performance than M-C- globally or on any domain measures, and M-C+ even performed better than M-C- on measures of learning, memory, and working memory. CONCLUSIONS: Our findings are consistent with prior work showing that methamphetamine use confers risk for worse neurocognitive outcomes, and that cannabis use does not appear to exacerbate and may even reduce this risk. People with a history of cannabis use disorders performed similarly to our nonsubstance using comparison group and outperformed them in some domains. These findings warrant further investigation as to whether cannabis use may ameliorate methamphetamine neurotoxicity.

Combined Cognitive and Psychological Interventions Improve Meaningful Outcomes after Acquired Brain Injury: A Systematic Review and Meta-Analysis.

Interventions addressing cognitive and emotional difficulties after acquired brain injury (ABI) often focus on specific impairments in cognition or mood. These interventions can be effective at addressing their specific target, but do not routinely translate to improved activity and participation outcomes. Approaches that combine cognitive and psychological rehabilitation are increasingly popular; however, to date, there have been no systematic evaluations of their efficacy. We conducted a systematic review of five databases, searching for randomised controlled trials of adults with diagnoses of non-progressive ABI at least 1-month post injury, in receipt of interventions that combined cognitive and psychological components compared to any control. Screening and data extraction were evaluated by two independent reviewers using a standardised protocol. Effect sizes were calculated using Hedge's g and estimated using a random-effects model. Risk of bias was assessed using the PEDro-P rating system, and quality of evidence evaluated using the grading of recommendation, assessment, development and evaluation (GRADE) approach. Thirteen studies were included in the meta-analysis (n = 684). There was an overall small-to-medium effect (g = 0.42) for combined interventions compared with controls, with gains maintained at 6-month follow-up. Improvements were observed at the level of impairment, activity, participation and quality of life. GRADE ratings and analyses investigating sensitivity, heterogeneity and publication bias indicated that these effects were robust. No a priori variables moderated these effects. Overall, this review provides strong evidence that combined cognitive and psychological interventions create meaningful change in the lives of people with ABI.

Reply to Augello, P.A.; Wu, J. Comment on "Rogers et al. The Combined Effects of Cannabis, Methamphetamine, and HIV on Neurocognition. Viruses 2023, 15, 674".

We thank Augello and Wu [...].

Kratom's Emergence and Persistence Within the US Polydrug Epidemic.

Purpose of Review: Use of "kratom" products, derived from the bioactive botanical Mitragyna speciosa have increased amidst US polydrug use epidemics. Kratom alkaloids interact with opioid, serotonergic, adrenergic, and other receptors and regular users have described experiencing a wide range of effects. Some with polydrug use histories have reported using kratom as a substitute for other drugs or to nonmedically self-manage substance use disorder (SUD) symptoms. Data describing this remain scare and come from self-report. We review this literature describing kratom use as a drug substitute, or as a nonmedical "self-treatment" for attenuating dependence or SUD symptoms. Recent Findings: Kratom products have been documented as being used as a licit and illicit opioid substitute. Use to reduce alcohol or stimulant consumption is less well documented. Although prior and current polydrug use appear common among a some kratom users, it is unclear if co-use is contemporaneous or concomitant. Temporal order of use initiation is typically undocumented. Use for energy and recreation are also increasingly reported. Summary: Data on kratom consumption come primarily from self-report with significant limitations. Until controlled human laboratory studies have been conducted, we can presently only describe what is known about human kratom use based on self-report. Such data describe real-world kratom use, leaving unaddressed human abuse liability or therapeutic potential of kratom alkaloids. Clinicians should be mindful of use motivations among people with SUD histories, sensitively assessing use. The paucity of data highlights the urgent need to increase funding and research for understanding kratom's effects in humans.

Cognitive and Motor Therapy After Stroke Is Not Superior to Motor and Cognitive Therapy Alone to Improve Cognitive and Motor Outcomes: New Insights From a Meta-analysis.

OBJECTIVE: To evaluate whether cognitive and motor therapy (CMT) is more effective than no therapy, motor therapy, or cognitive therapy on motor and/or cognitive outcomes after stroke. Additionally, this study evaluates whether effects are lasting and which CMT approach is most effective. DATA SOURCES: AMED, EMBASE, MEDLINE/PubMed, and PsycINFO databases were searched in October 2022. STUDY SELECTION: Twenty-six studies fulfilled the inclusion criteria: randomized controlled trials published in peer-reviewed journals since 2010 that investigated adults with stroke, delivered CMT, and included at least 1 motor, cognitive, or cognitive-motor outcome. Two CMT approaches exist: CMT dual-task ("classical" dual-task where the secondary cognitive task has a distinct goal) and CMT integrated (where cognitive components of the task are integrated into the motor task). DATA EXTRACTION: Data on study design, participant characteristics, interventions, outcome measures (cognitive/motor/cognitive-motor), results and statistical analysis were extracted. Multilevel random effects meta-analysis was conducted. DATA SYNTHESIS: CMT demonstrated positive effects compared with no therapy on motor outcomes (g=0.49; 95% confidence interval [CI], 0.10, 0.88) and cognitive-motor outcomes (g=0.29; 95% CI, 0.03, 0.54). CMT showed no significant effects compared with motor therapy on motor, cognitive, and cognitive-motor outcomes. A small positive effect of CMT compared with cognitive therapy on cognitive outcomes (g=0.18; 95% CI, 0.01, 0.36) was found. CMT demonstrated no follow-up effect compared with motor therapy (g=0.07; 95% CI, -0.04, 0.18). Comparison of CMT dual-task and integrated revealed no significant difference for motor (F1,141=0.80; P=.371) or cognitive outcomes (F1,72=0.61, P=.439). CONCLUSIONS: CMT was not superior to monotherapies in improved outcomes after stroke. CMT approaches were equally effective, suggesting that training that enlists a cognitive load per se may benefit outcomes.

Continuous non-invasive estimates of cerebral blood flow using electrocardiography signals: a feasibility study.

This paper describes a potential method to detect changes in cerebral blood flow (CBF) using electrocardiography (ECG) signals, measured across scalp electrodes with reference to the same signal across the chest-a metric we term the Electrocardiography Brain Perfusion index (EBPi). We investigated the feasibility of EBPi to monitor CBF changes in response to specific tasks. Twenty healthy volunteers wore a head-mounted device to monitor EBPi and electroencephalography (EEG) during tasks known to alter CBF. Transcranial Doppler (TCD) ultrasound measurements provided ground-truth estimates of CBF. Statistical analyses were applied to EBPi, TCD right middle cerebral artery blood flow velocity (rMCAv) and EEG relative Alpha (rAlpha) data to detect significant task-induced changes and correlations. Breath-holding and aerobic exercise induced highly significant increases in EBPi and TCD rMCAv (p < 0.01). Verbal fluency also increased both measures, however the increase was only significant for EBPi (p < 0.05). Hyperventilation induced a highly significant decrease in TCD rMCAv (p < 0.01) but EBPi was unchanged. Combining all tasks, EBPi exhibited a highly significant, weak positive correlation with TCD rMCAv (r = 0.27, p < 0.01) and the Pearson coefficient between EBPi and rAlpha was r = - 0.09 (p = 0.05). EBPi appears to be responsive to dynamic changes in CBF and, can enable practical, continuous monitoring. CBF is a key parameter of brain health and function but is not easily measured in a practical, continuous, non-invasive fashion. EBPi may have important clinical implications in this context for stroke monitoring and management. Additional studies are required to support this claim. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-023-00265-z.

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) 2023 APA, all rights reserved).

The Combined Effects of Cannabis, Methamphetamine, and HIV on Neurocognition.

OBJECTIVE: Methamphetamine and cannabis are two widely used substances among people living with HIV (PLWH). Whereas methamphetamine use has been found to worsen HIV-associated neurocognitive impairment, the effects of combined cannabis and methamphetamine use disorder on neurocognition in PLWH are not understood. In the present study, we aimed to determine the influence of these substance use disorders on neurocognition in PLWH and to explore if methamphetamine-cannabis effects interacted with HIV status. METHOD AND PARTICIPANTS: After completing a comprehensive neurobehavioral assessment, PLWH (n = 472) were stratified by lifetime methamphetamine (M-/M+) and cannabis (C-/C+) DSM-IV abuse/dependence disorder into four groups: M-C- (n = 187), M-C+ (n = 68), M+C-, (n = 82), and M+C+ (n = 135). Group differences in global and domain neurocognitive performances and impairment were examined using multiple linear and logistic regression, respectively, while holding constant other covariates that were associated with study groups and/or cognition. Data from participants without HIV (n = 423) were added, and mixed-effect models were used to examine possible interactions between HIV and substance use disorders on neurocognition. RESULTS: Compared with M+C+, M+C- performed worse on measures of executive functions, learning, memory, and working memory and were more likely to be classified as impaired in those domains. M-C- performed better than M+C+ on measures of learning and memory but worse than M-C+ on measures of executive functions, learning, memory, and working memory. Detectable plasma HIV RNA and nadir CD4 < 200 were associated with lower overall neurocognitive performance, and these effects were greater for M+C+ compared with M-C-. CONCLUSIONS: In PLWH, lifetime methamphetamine use disorder and both current and legacy markers of HIV disease severity are associated with worse neurocognitive outcomes. There was no evidence of an HIV × M+ interaction across groups, but neurocognition was most impacted by HIV among those with polysubstance use disorder (M+C+). Better performance by C+ groups is consistent with findings from preclinical studies that cannabis use may protect against methamphetamine's deleterious effects.

Development of complex executive function over childhood: Longitudinal growth curve modeling of performance on the Groton Maze Learning Task.

This longitudinal study modeled children's complex executive function (EF) development using the Groton Maze Learning Task (GMLT). Using a cohort-sequential design, 147 children (61 males, 5.5-11 years) were recruited from six multicultural primary schools in Melbourne and Perth, Australia. Race/ethnicity data were not available. Children were assessed on the GMLT at 6-month intervals over 2-years between 2010 and 2012. Growth curve models describe age-related change from 5.5 to 12.5 years old. Results showed a quadratic growth trajectory on each measure of error-that is, those that reflect visuospatial memory, executive control (or the ability to apply rules for action), and complex EF. The ability to apply rules for action, while a rate-limiting factor in complex EF, develops rapidly over early-to-mid childhood.

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.

Evaluating the feasibility and acceptability of the Mood Assessment Post-Stroke (MAPS) mood screening training.

Mood problems are common after stroke, and screening is recommended. Training may support staff knowledge and implementation of screening, but the feasibility of training programmes in the Australian healthcare system has not been formally established. This study aimed to assess the feasibility of a mood screening training for a multidisciplinary team (MDT) of stroke clinicians working in a post-acute inpatient rehabilitation service.Twelve staff from a rehabilitation service at a major hospital in Sydney, Australia participated in a 3-h interactive training session. The feasibility of running the course, assessment of knowledge gained via a consolidation exercise and quiz and acceptability of the training were assessed via focus groups.The in-person modality of the training hindered recruitment and assessment of participants' knowledge, though the actual measures themselves appeared appropriate. Nine participants provided feedback in two focus groups. Thematic analysis identified positive reactions to the training. However, low self-efficacy persisted and organisational/socio-cultural barriers to implementation emerged. Following training, the medical officers of the MDT had successfully implemented routine screening.Overall, the training appeared acceptable and to foster knowledge in staff. However, limitations to recruitment and administering evaluations were identified. The development of flexible online training may improve future evaluations of screening training programmes/pathways.

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.

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.

Searching for a Signal: Self-Reported Kratom Dose-Effect Relationships Among a Sample of US Adults With Regular Kratom Use Histories.

There is limited understanding regarding kratom use among US adults. Although motivations for use are increasingly understood, typical kratom doses, threshold of (low and high) doses for perceived effectiveness, and effects produced during cessation are not well documented. We aimed to extend prior survey work by recruiting adults with current and past kratom exposure. Our goal was to better understand kratom dosing, changes in routines, and perception of effects, including time to onset, duration, and variability of beneficial and adverse outcomes from use and cessation. Among respondents who reported experiencing acute kratom effects, we also sought to determine if effects were perceived as helpful or unhelpful in meeting daily obligations. Finally, we attempted to detect any signal of a relationship between the amount of kratom consumed weekly and weeks of regular use with ratings of beneficial effects from use and ratings of adverse effects from cessation. We conducted an online survey between April-May 2021 by re-recruiting participants from a separate study who reported lifetime kratom use. A total of 129 evaluable surveys were collected. Most (59.7%) had used kratom >100 times and reported currently or having previously used kratom >4 times per week (62 weeks on average). Under half (41.9%) reported that they considered themselves to be a current "regular kratom user." A majority (79.8%) reported experiencing acute effects from their typical kratom dose and that onset of effects began in minutes but dissipated within hours. Over a quarter reported that they had increased their kratom dose since use initiation, whereas 18.6% had decreased. Greater severity of unwanted effects from ≥1 day of kratom cessation was predicted by more weeks of regular kratom use (ß = 6.74, p = 0.02). Acute kratom effects were largely reported as compatible with, and sometimes helpful in, meeting daily obligations. In the absence of human laboratory studies, survey methods must be refined to more precisely assess dose-effect relationships. These can help inform the development of controlled observational and experimental studies needed to advance the public health understanding of kratom product use.

Assessment of Kratom Use Disorder and Withdrawal Among an Online Convenience Sample of US Adults.

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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.