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A recent article in Frontiers in Psychiatry examines the presence of kratom in opioid overdose deaths, based on a toxicological report from a coroner. Kratom, a botanical product, has gained attention in the US due to reports of adverse effects and fatalities. While kratom is unregulated at the federal level in the US, it is considered illegal in some European and Southeast Asian countries. The article highlights some issues with the report, such as the misinterpretation of a blood concentration as a lethal dose. It also discusses the complexities of kratom use, the lack of established lethal doses, and the need for accurate information and documentation. The authors stress the importance of federal oversight to establish safe dosing recommendations and regulations for kratom products, ensuring consumer access to safe and properly labeled products. The article provides information about the authors' contributions, funding sources, conflicts of interest, and a disclaimer that the views expressed are solely those of the authors. [Extracted from the article]

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 possiblemanifestation 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. [ABSTRACT FROM AUTHOR]

Co-use of non-medical opioids (NMO) and methamphetamine is increasing. So too is the use of the psychoactive botanical "kratom," including among people with NMO and methamphetamine use histories. We assessed characteristics associated with respondent groups who reported lifetime methamphetamine and/or kratom use within a nationally representative US sample using 2019 National Survey on Drug Use and Health data from respondents reporting lifetime NMO use (diverted prescription opioids, heroin). Weighted prevalence estimates for demographic, mental health, and substance use outcomes were determined. Logistic regression examined associations between group membership and outcomes. Among this sample of respondents with lifetime NMO use, 67.6% (95% CI = 65.6–69.4%) reported only NMO use; 4.6% (3.9–5.4%) reported NMO+Kratom; 24.7% (22.7–26.7%) reported NMO+Methamphetamine; and 3.2% (2.5–3.9%) reported NMO+Methamphetamine+Kratom. Compared to those in the NMO-only group, the NMO+Kratom group was more likely to report past-year serious mental illness (SMI; OR = 2.27), suicidality (OR = 1.89), and past-month psychological distress (OR = 1.88). The NMO+Methamphetamine+Kratom group was more likely to report past-year SMI (OR = 2.65), past-month psychological distress (OR = 2.06), and unmet mental health needs (OR = 2.03); increased odds for drug injection, opioid withdrawal, and perceived treatment need also emerged. Risk factors were observed for all groups but were greatest among those reporting use of all three substances. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

Kratom products available in the United States are becoming increasingly diverse both in terms of content and in terms of how they are marketed. Prior survey research indicates that kratom has been primarily used in the US to self-treat anxiety, depression, pain, fatigue, and substance use disorder (SUD) symptoms. Kratom is also well-known for its use as a short- or long-term full opioid agonist substitute. Therefore, use may be greater in regions particularly impacted by addiction to prescription opioids. Use may also be greater in demographic groups targeted by media outlets (such as specific podcasts) in which kratom is touted. Here, we aimed to determine whether lifetime and past-year kratom use were associated with region of residence and with being young, White, post-secondary educated, and employed. To strengthen confidence in our findings, we analyzed data from two sources: our own crowdsourced online convenience sample and the 2019 National Survey on Drug Use and Health (NSDUH). In our sample (N = 2,615), 11.1% reported lifetime and 6.7% reported past-year kratom use, and the odds of kratom use were higher among people who were White, younger, at least high school educated, employed, and above the poverty line, as well as those reporting nonmedical opioid use, past-year SUD, or lifetime SUD treatment; residence was not a significant predictor. In NSDUH data, suburban residence and other demographic factors, concordant with those from the crowdsourced sample, were associated with kratom use. Taken together, the findings support a general "White middle-class suburban" profile of the modal kratom user, but more research is needed to understand it. In the interim, focus should be on our finding that lifetime nonmedical opioid use was associated with an up to five times greater likelihood of past-year kratom use, suggesting that drug-use history may presently be the strongest predictor of kratom use. [ABSTRACT FROM AUTHOR]

Background: Originally believed to be an atypical antidepressant acting at serotonin transporters, tianeptine is now known to also be an atypical agonist at mu-opioid receptors. Its nonmedical use may be increasing amidst the broader context of novel drug and supplement use. Objectives: To analyze social-media text from current, former, and prospective tianeptine users for better understanding of their conceptualizations of tianeptine, motives for and patterns of use, and reported benefits and harms. Methods: Reddit posts were obtained and thematically coded; additional quantitative analyses were conducted. Results: A total of 210 posts mentioning tianeptine were made between 2012 and 2020. Eighteen thematic categories were identified, 10 of which were consistent with expected themes. Two independent raters coded all text, generating 1,382 unique codes, of which 1,090 were concordant (78.9% interrater agreement). Tianeptine use was frequently associated with use of other drugs, particularly kratom, phenibut, and racetams. People conceptualized and variously used tianeptine as an opioid, antidepressant, and "nootropic" (cognitive enhancer). Between 2014 and 2020, mentions of positive effects decreased, while mentions of adverse effects and withdrawal increased. Motivations for use included substitution or withdrawal mitigation for other drugs (especially opioids) and for kratom itself; self-treatment for psychiatric symptoms; and improvement of quality of life, mood, or performance. Descriptions of tolerance, withdrawal, and addiction were evident. Intravenous use was rare and strongly discouraged, with detrimental effects described. Conclusion: Tianeptine is recognized as an opioid (though not only an opioid) in online communities. Posts describe benefits, acute risks, and patterns of co-use that warrant greater clinical attention. [ABSTRACT FROM AUTHOR]

Background: Corrections-involved adults with a history of opioid use disorder are at elevated risk of opioid overdose following release from correctional settings. Increased opioid prescribing restrictions and monitoring during a time when heroin is becoming cheaper and ubiquitous means that adults who misused prescription opioids prior to incarceration may be reentering communities at greater risk for heroin exposure and use.Objectives: Determine risk factors of post-release heroin use among a sample of adults who participated in corrections-based drug treatment in Kentucky released between 2012 and 2017.Methods: Survey data obtained as part of an ongoing evaluation of corrections-based drug treatment were examined.Results: The final sample (N = 1,563) was majority male (80.9%). Nearly 11.0% reported past-year heroin use following their release. Depressive symptoms, polydrug use, and urban proximity were more common among participants reporting post-release heroin use. Heroin use 30 days prior to incarceration was associated with a 432.1% increase in odds of heroin use subsequent to incarceration. Post-release suicidal ideation increased odds of heroin use by 154.2%, whereas reporting satisfaction from social interactions decreased odds of use by nearly 60%. Post-release use of cocaine and diverted buprenorphine were associated with increased likelihood of heroin use during this time period, increasing odds by 469.1% and 265.9%, respectively. Residing in Central Appalachia subsequent to incarceration was associated with decreased likelihood of use.Conclusions: In this sample, post-release heroin use was associated with concerning features, such as polydrug use, lack of social satisfaction, and suicidal ideation. These features can serve as clear targets for clinical intervention. [ABSTRACT FROM AUTHOR]

Background: Kratom use in the West has increased recently, yet the prevalence and motives for use among individuals with a history of substance use disorder (SUD) have not been fully examined. Kratom has been documented as a means of treating chronic pain, mitigating drug dependence, and easing withdrawal symptoms, yet it is unclear if substance users are utilizing kratom as a self-medication. Abuse liability, side effects, and overall appeal of kratom remain uncertain.Methods: In April 2017, an anonymous survey regarding kratom use and motivations was completed by clients enrolled in a 12-Step-oriented residential program. 500 respondents with a self-reported history of SUD completed the survey.Results: 20.8% of respondents endorsed lifetime kratom use and 10.2% reported past-12-month use. Kratom-users were younger (=32.1 vs. 35.9, p<0.001) and were more versatile substance users. A majority (68.9%) of kratom-users reported having used the drug as a means of reducing or abstaining from non-prescription opioids (NPO) and/or heroin, and 64.1% reported using kratom as a substitute for NPO/heroin. 18.4% of kratom-users reported using the drug due to a disability or chronic pain. One-third of kratom-users stated that kratom was a helpful substance and that they would try it again. However, kratom was not preferred and was indicated as having less appeal than NPO, heroin, amphetamines, and Suboxone.Conclusions: Among substance users, kratom use may be initiated for a variety of reasons, including as a novel form of harm-reduction or drug substitution, particularly in the context of dependence and withdrawal from other substances. [ABSTRACT FROM AUTHOR]

Opioid analgesics are commonly administered to hospitalized patients to treat acute pain, but these drugs put patients at risk for serious adverse events, such as unintended advancing sedation, respiratory depression, and death. Nurses play an important role in keeping patients safe by making clinical decisions about the frequency and intensity with which patients receivings and epidural opioids should be monitored. To make sound clinical judgments, nurses must be aware of the factors that place patients at elevated risk for adverse opioid-related effects and know how to screen and assess patients for these risks. The authors review the literature on unintended advancing sedation and respiratory depression associated with opioid administration and present evidence-based recommendations for clinical decision making and patient monitoring, using both nursing assessments and electronic technologies. [ABSTRACT FROM AUTHOR]

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

Background: Mitragyna speciosa, referred to as "kratom", is increasingly used in the United States for self-treating pain, psychiatric, and substance use disorder symptoms. It is used by some to attenuate opioid withdrawal and as a longer-term drug substitute. Most self-report data have come from online surveys, small in-person surveys, and case reports. These may not be representative of the broader kratom-using population.Purpose: Analyze user-generated social media posts to determine if independent, descriptive accounts are generally consistent with prior U.S. kratom survey findings and gain a more nuanced understanding of kratom use patterns.Methods: Reddit posts mentioning kratom from 42 subreddits between June 2019-July 2020 were coded by two independent raters.Findings: Relevant posts (number of comments, upvotes, and downvotes) from 1274 posts comprised the final sample (n = 280). Of the 1521 codes applied, 1273 (83.69%) were concordant. Desirable kratom effects were described among a majority, but so too were adverse effects. Reports of kratom as acute self-treatment for opioid withdrawal were more prominent compared to longer-term opioid substitution. Quantitative analysis found higher kratom doses associated (p < .001) with greater odds of reported kratom addiction (OR = 3.56) or withdrawal (OR = 5.88), with slightly lower odds of desirable effects (OR = 0.53, p = .014). Despite perceived therapeutic benefits, kratom was characterized by some in terms of addiction that, in some cases, appeared dose-dependent. Polydrug use was also prominently discussed.Conclusions: Results validated many prior survey findings while illustrating complexities of kratom use that are not being fully captured and require continued investigation. [ABSTRACT FROM AUTHOR]

Within addiction science, incubation of craving is an operational label used to describe time-dependent increases in drug seeking during periods of drug deprivation. The purpose of this systematic review was to describe the preclinical literature on incubation of craving and the clinical literature on craving measured over extended periods of abstinence to document this translational homology and factors impacting correspondence. Across the 44 preclinical studies that met inclusion criteria, 31 reported evidence of greater lever pressing, nose pokes, spout licks, or time spent in drug-paired compartments (i.e., drug seeking) relative to neutral compartments after longer periods of abstinence relative to shorter periods of abstinence, labelled as "incubation of craving." In contrast, no clinical studies (n = 20) identified an increase in opioid craving during longer abstinence periods. The lack of clinical evidence for increases in craving in clinical populations weakens the translational utility of operationalizing the time-dependent increase in drug-seeking behavior observed in preclinical models as models of incubation of "craving". • Incubation of opioid craving is not observed in clinical research. • Opioid craving decreases in humans over time during periods of abstinence. • The translational utility of the incubation of craving model needs refinement. [ABSTRACT FROM AUTHOR]

Background: Kratom, a Southeast Asian plant with opioid-receptor mediated effects, has emerged as a potential substance of abuse, with limited data on its use and effects. This study characterized kratom user demographics, use patterns, and perceived drug effects.Methods: A cross-sectional, anonymous online survey was conducted between January and December 2017.Results: 2,798 kratom users - mean age 40 (SD = 12); predominantly White (90 %), female (61 %), and located in the US (97 %) - completed the survey. Kratom was primarily taken orally in doses of 1-3 g (49 %), with daily use (59 %) being most common. Kratom was used for pain (91 %), anxiety (67 %), and depression (65 %), with high ratings of effectiveness. 1,144 (41 %) used kratom to stop or reduce prescription or illicit opioid use, citing decreased opioid withdrawal and craving related to kratom use, with 411 reporting >1-year continuous abstinence from opioids attributed to kratom use. Roughly one-third of respondents reported adverse effects of kratom, largely rated as mild in severity and lasting ≤24 h. Seventeen participants (0.6 %) sought treatment for adverse effects. Fifty-six individuals (2 %) met DSM-5 criteria for a past-year moderate or severe kratom-related substance use disorder (SUD). When asked how troubled they felt regarding their kratom use, the mean (SD) rating was 3.2 (9.8) on a scale from 0 to 100.Conclusion: Kratom is used among White, middle-aged Americans for symptoms of pain, anxiety, depression, and opioid withdrawal. Although regular use was typical, kratom-related SUD and serious adverse effects were uncommon. Additional research on kratom epidemiology and pharmacology is imperative in light of the present opioid epidemic. [ABSTRACT FROM AUTHOR]