Article

Patterns of Kratom use and health impact in the US − Results from an online survey

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Abstract

Background: Kratom preparations have raised concerns of public health and safety in the US. Investigation into the demographics, perceived beneficial and detrimental effects of Kratom as well as common doses and purposes of its use are important to properly evaluate its potential health impact. Methods: An anonymous cross-sectional online survey was conducted in October 2016 of 10,000 current Kratom users through available social media and online resources from the American Kratom Association. A total of 8049 respondents completed the survey. Results: Kratom is primarily used by a middle-aged (31-50 years), middle-income ($35,000 and above) population for purposes of self-treating pain (68%) and emotional or mental conditions (66%). Kratom preparations present with a dose-dependent effect with negative effects, which were primarily gastrointestinal related including nausea and constipation, mainly presenting at high (5g or more/dose) and more frequent (22 or more doses/week) dosing. Conclusions: Kratom shows a dose-dependent opioid-like effect providing self-reported perceived beneficial effects in alleviating pain and relieving mood disorders. Kratom was primarily used for self-treatment of pain, mood disorders, and withdrawal symptoms associated with prescription opioid use.

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... Surveys and case studies reveal a growing trend of Americans using kratom for self-medication, addressing conditions such as pain and opioid withdrawal (Boyer et al., 2007;Coe et al., 2019;Grundmann, 2017;Henningfield et al., 2018;Smith and Lawson, 2017;Swogger et al., 2015). Despite this trend, the therapeutic benefits of such use lack robust empirical support. ...
... Despite this trend, the therapeutic benefits of such use lack robust empirical support. Kratom is recognized as a substitute for opioids and a remedy for opioid withdrawal in both Southeast Asia (SEA) and the US (Boyer et al., 2008;Coe et al., 2019;Grundmann, 2017;Vicknasingam et al., 2010;). Internet-based studies highlight prevalent usage patterns in the US, primarily among White, middle-aged, middleincome, and college-educated individuals. ...
... Internet-based studies highlight prevalent usage patterns in the US, primarily among White, middle-aged, middleincome, and college-educated individuals. They commonly use kratom for pain treatment, opioid withdrawal, and mental health conditions, reporting minor, dose-dependent adverse effects like stomach upset (Grundmann, 2017;Henningfield et al., 2018;Swogger et al., 2015). Furthermore, US-based internet studies indicate that kratom use is notably prevalent among White, middle-aged, middle-income, and collegeeducated individuals, who often consume it for pain treatment, opioid withdrawal, and mental health conditions, experiencing minor, dose-dependent adverse effects such as stomach upset (Grundmann, 2017;Henningfield et al., 2018;Swogger et al., 2015). ...
Article
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Tertiary students' knowledge of kratom predominantly focuses on its effects and legal implications, overlooking the crucial understanding of different kratom leaf veins. Recognizing these vein types is essential for comprehending the potential consequences of kratom misuse. This study addresses concerns about the likelihood of tertiary students engaging in kratom abuse due to its easy accessibility and affordability. This study aims to evaluate the knowledge levels of three types of kratom veins inhalants—white, red, and green—among male and female tertiary students, utilizing a cross-sectional design with quantitative data collected from 296 students through Google Forms. The analysis reveals gender-based disparities in knowledge percentages for each vein type. The analysis presented in Figure 1 accentuates significant disparities in knowledge levels between male and female respondents regarding various colours of kratom veins. Notably, males consistently exhibit superior knowledge, with a substantial percentage of 19.9% for the white vein compared to their female counterparts. This trend persists with the red vein, where males outperform females, achieving a knowledge percentage of 15.9%, indicating a persistent gender-based difference in understanding kratom vein colours among tertiary students. The examination extends to the green vein, with males demonstrating a higher knowledge percentage of 10.1% compared to females. Despite the widespread use of kratom, particularly among adolescents in substance abuse, a substantial knowledge gap exists among tertiary students regarding various kratom vein types. Tailoring educational efforts to consider these multifaceted factors is crucial for promoting inclusivity, equitable knowledge distribution, and fostering a comprehensive understanding of kratom within diverse populations. Abstrak: Pengetahuan pelajar-pelajar tertiari tentang kratom lebih cenderung kepada kesan dan implikasi undang-undang, dengan memahami pemahaman yang penting mengenai pelbagai jenis urat daun kratom. Pemahaman terhadap jenis-jenis urat ini adalah kunci untuk memahami kesan pengaruh kratom. Kajian ini menimbulkan kebimbangan mengenai kemungkinan pelajar tertiari terlibat dalam pengaruh dan harga yang mampu disebabkan kemudahan. Objektif kajian adalah menilai tahap pengetahuan terhadap tiga jenis urat kratom - putih, merah, dan hijau - di kalangan pelajar lelaki dan perempuan tertiari. Reka bentuk rentas-seksyen digunakan dengan mengumpulkan data kuantitatif daripada 296 pelajar melalui Google Forms. Analisis menunjukkan perbezaan berdasarkan jantina dalam peratusan pengetahuan bagi setiap jenis urat. Rajah 1 menunjukkan perbezaan yang ketara dalam tahap pengetahuan antara responden lelaki dan perempuan mengenai pelbagai warna urat kratom. Lelaki menunjukkan pengetahuan yang lebih tinggi secara konsisten, dengan peratusan ketara sebanyak 19.9% untuk urat putih berbanding perempuan. Trend ini berterusan dengan urat merah, di mana lelaki melebihi perempuan, mencapai peratusan pengetahuan sebanyak 15.9%, menunjukkan perbezaan yang berterusan berdasarkan jantina dalam pemahaman warna urat kratom di kalangan pelajar tertiari. Pemeriksaan melibatkan urat hijau, dengan lelaki menunjukkan peratusan pengetahuan yang lebih tinggi sebanyak 10.1% berbanding dengan perempuan. Walaupun penggunaan kratom yang meluas, terutamanya di kalangan remaja dalam pengaruh bahan, terdapat jurang pengetahuan yang besar di kalangan pelajar tertiari mengenai pelbagai jenis urat kratom. Penyesuaian usaha pendidikan untuk mengkaji faktor-faktor yang berbeza ini adalah penting untuk mempromosikan inklusiviti, pengagihan pengetahuan yang saksama, dan memahami pemahaman yang menyeluruh tentang kratom dalam kalangan populasi yang pelbagai.
... [9] The potential for dependence and withdrawal symptoms akin to opioid withdrawal is a significant concern, necessitating careful assessment and monitoring by clinicians. [10] Additionally, the variability in the alkaloid content of Kratom products can lead to unpredictable effects and risks. [11] Although Kratom use first showed an increase in 2007, the rapid expansion of available Kratom products has fueled continued increases in use since at least 2015, [12] leading to hundreds of fatalities in an unregulated U.S. trade market. ...
... • Gradual tapering of Kratom under medical supervision to mitigate withdrawal symptoms. [9,10] • Symptomatic treatment for withdrawal, including clonidine for autonomic hyperactivity, nonsteroidal anti-inflammatory drugs for myalgia, and antiemetics for gastrointestinal distress. [6] • Consideration of adjunct medications such as gabapentin for anxiety and sleep disturbances related to withdrawal. ...
... Long-term management • Regular monitoring of liver function and overall health, including routine blood tests and physical assessments. [9,10] • Ongoing psychological support through individual therapy, focusing on coping strategies and relapse prevention. [6,18] • Referral to addiction specialists for comprehensive addiction treatment, including potential participation in support groups or 12-step programs. ...
Article
The rising use of Kratom and Delta-8-tetrahydrocannabinol (Delta-8-THC) poses new challenges for advanced practice registered nurses (APRNs). This article explores the increasing prevalence of these substances, driven by limited federal regulation and inconsistent state laws, which lead to their widespread availability and appeal to vulnerable populations. Kratom, from the Mitragyna speciosa tree, contains psychoactive compounds that mimic opioids and affect various neurotransmitter systems. Delta-8-THC, a milder cannabinoid from hemp or cannabis, remains unregulated and raises safety concerns. This review covers their pharmacological profiles, potential for abuse, and clinical implications, including a case study of Kris T., a 16-year-old gender nonconforming individual, highlighting dependence, withdrawal, and cognitive issues. APRNs need to understand these substances' dual actions and abuse potential, emphasizing evidence-based screening, individualized treatments, and advocacy for regulation to ensure safety and efficacy.
... According to the literature, kratom has been used to alleviate pain, decrease fatigue, and elevate mood [2,3]. Furthermore, it has been recently used to help alleviate the unpleasant experience associated with opioid withdrawal [4,5]. However, kratom could have many potential health consequences [3], including fatal incidents and potential toxicity [6]. ...
... Several studies have examined the benefits and adverse effects associated with kratom use. Grundmann [5] stated that kratom is mainly used for acute or chronic pain, and helping with emotional or mental conditions such as anxiety, depression, or PTSD. Boyer Given the limited studies on kratom use, this study aims to utilize social media data to understand the benefits and adverse effects of kratom as reported by potential users. ...
... This research expanded the existing literature on the use of social media data to address the benefits and health impacts of kratom. In terms of benefits, the findings inform the existing literature that reported health benefits of kratom use like chronic pain relief and pain management [5,6,10,22,48,49], addiction and opiate withdrawal [5,[13][14][15]22,48], anxiety and depression relief [5,10], help falling asleep [50], improving sex drive [22,49,51,52], improving mental health and quality of life [11,12,52], and improving mood and energy [12,13,15,52]. Overall, the results revealed that kratom helps with easing aches, relieving and reducing pain, managing pain, overcoming and easing unpleasant adverse effects of opioid addiction and withdrawal, self-treating symptoms of depression and anxiety, inducing sleep and treating sleep disorders like insomnia, enhancing sexual performance, increasing sex drive and desire, boosting libido, helping with mental health woes, helping with emotional or mental conditions, helping to cope with stressful life events, and boosting mood and increases in body energy. ...
Article
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Background: Kratom is a substance that alters one’s mental state and is used for pain relief, mood enhancement, and opioid withdrawal, despite potential health risks. In this study, we aim to analyze the social media discourse about kratom to provide more insights about kratom’s benefits and adverse effects. Also, we aim to demonstrate how algorithmic machine learning approaches, qualitative methods, and data visualization techniques can complement each other to discern diverse reactions to kratom’s effects, thereby complementing traditional quantitative and qualitative methods. Methods: Social media data were analyzed using the latent Dirichlet allocation (LDA) algorithm, PyLDAVis, and t-distributed stochastic neighbor embedding (t-SNE) technique to identify kratom’s benefits and adverse effects. Results: The analysis showed that kratom aids in addiction recovery and managing opiate withdrawal, alleviates anxiety, depression, and chronic pain, enhances mood, energy, and overall mental well-being, and improves quality of life. Conversely, it may induce nausea, upset stomach, and constipation, elevate heart risks, affect respiratory function, and threaten liver health. Additional reported side effects include brain damage, weight loss, seizures, dry mouth, itchiness, and impacts on sexual function. Conclusion: This combined approach underscores its effectiveness in providing a comprehensive understanding of diverse reactions to kratom, complementing traditional research methodologies used to study kratom.
... Kratom has become increasingly commercially available in the USA [5][6][7][8][9] and is often marketed as an opioid alternative or as a method to alleviate opioid withdrawal symptoms, despite limited evidence [10][11][12][13][14][15][16]. Kratom is derived from the leaves of the Mitragyna speciosa tree native to Southeast Asia and is available in various forms, including dried leaves, powdered extracts, and capsules [5,6,[8][9][10]. ...
... Kratom has become increasingly commercially available in the USA [5][6][7][8][9] and is often marketed as an opioid alternative or as a method to alleviate opioid withdrawal symptoms, despite limited evidence [10][11][12][13][14][15][16]. Kratom is derived from the leaves of the Mitragyna speciosa tree native to Southeast Asia and is available in various forms, including dried leaves, powdered extracts, and capsules [5,6,[8][9][10]. Its primary active ingredients are mitragynine and 7-hydroxymitragynine [17] which interact with opioid receptors in the brain, influencing pain perception, mood, and other physiological responses [18,19]. ...
... Because kratom is federally unregulated, it is often untested for potency, purity, and product safety, leaving consumers vulnerable to contaminated or toxic products and overconsumption [20,21]. While kratom may have a lower abuse liability than opioids [22], research indicates that chronic or high-dose kratom use may have a negative impact on health, including seizures, heart problems, gastrointestinal and liver disorders/injury, coma, and death [6,[23][24][25][26][27][28][29][30]. Indeed, there has been an increasing number of kratom-related calls to US Poison Control Centers [31,32]. ...
Article
Kratom is federally unregulated and is marketed as an opioid alternative despite limited evidence and known negative effects. Disparities in associations between opioid and kratom use may be partly attributed to race/ethnicity and sexual orientation given differences in marketing, use motives, and prescriber practices. Data: 2021 nationally representative National Survey on Drug Use and Health among individuals aged 18 + . We used weighted logistic regression analyses to assess race/ethnicity and sexual orientation as moderators of associations between past-year opioid (1) use (total sample, n = 44,877) and (2) misuse and use disorder (among those with past-year opioid use, n = 10,398) and the outcome of kratom use (lifetime, past year). 26.76% reported past-year opioid use, and among those, 12.20% and 7.54% reported past-year opioid misuse and use disorder, respectively; 1.72% and 0.67% had lifetime and past-year kratom use, respectively. Opioid use was positively associated with lifetime (aOR = 2.69, 95%CI = 1.98, 3.66) and past-year (aOR = 3.84, 95%CI = 2.50, 5.92) kratom use; associations among non-Hispanic Black and Hispanic (vs. non-Hispanic White) participants were weaker (p < 0.01). Among participants reporting past-year opioid use, misuse and use disorder were positively associated with lifetime (aORmisuse = 2.46, 95%CI = 1.60, 3.78; aORuse disorder = 5.58, 95%CI = 2.82, 11.04) and past-year (aORmisuse = 2.40, 95%CI = 1.26, 4.59; aORuse disorder = 3.08, 95%CI = 1.48, 6.41) kratom use; among bisexual (vs. heterosexual) participants, opioid use disorder was associated with a lower probability of lifetime kratom use (p < 0.01). We observed positive associations between opioid and kratom use, with potential disparities among certain racial/ethnic and sexual orientation groups. Research should examine the mechanisms contributing to these differences to inform prevention and intervention efforts.
... People who use kratom report doing so for a variety of purposes such as pain relief, relaxation, or to boost energy Swogger et al. 2015). However, the decision to use kratom among individuals with opioid use disorder has been associated with limited access to treatment (Anand and Hosanagar 2022) and kratom is commonly used to self-treat symptoms of addiction to opioids, including mitigation of withdrawal symptoms (Grundmann 2017). Kratom is also used as a substitute for opioids, alcohol, or stimulant drugs and is perceived as a safer alternative to these substances (Grundmann 2017;. ...
... However, the decision to use kratom among individuals with opioid use disorder has been associated with limited access to treatment (Anand and Hosanagar 2022) and kratom is commonly used to self-treat symptoms of addiction to opioids, including mitigation of withdrawal symptoms (Grundmann 2017). Kratom is also used as a substitute for opioids, alcohol, or stimulant drugs and is perceived as a safer alternative to these substances (Grundmann 2017;. Motivations for kratom use also include the selftreatment of anxiety and depression (Grundmann 2017;. ...
... Kratom is also used as a substitute for opioids, alcohol, or stimulant drugs and is perceived as a safer alternative to these substances (Grundmann 2017;. Motivations for kratom use also include the selftreatment of anxiety and depression (Grundmann 2017;. ...
... The most commonly reported reasons for use in the United States are generally similar to those reported in Southeast Asia field studies and surveys (Singh et al., 2019b), although these studies do not provide nationally representative estimates of the reasons for use. For example, surveys with a targeted focus on people with opioid use histories (e.g., Coe et al., 2019;Garcia-Romeu et al., 2020), or male sexual health issues (Deebel et al., 2023) may overestimate reasons for use related to such issues, compared to surveys based on convenience sampling of current, active kratom consumers, irrespective of use motivation (Grundmann, 2017;Grundmann et al., 2023). Overall, survey and social media selfreport are consonant with the approximately 20,000 consumer comments made to Drug Enforcement Administration (DEA) after its proposal to schedule kratom in the Controlled Substances Act (CSA) in 2016, where myriad reasons for use were described, such as sleep improvement, or symptom management for posttraumatic stress disorder (PTSD), fibromyalgia, depression, insomnia, substance use disorders (SUDs), and pain (DEA, 2016;Smith et al., 2021;Smith et al., 2022c;Smith et al., 2024). ...
... This is similar to recent findings that among some long-term consumers, those taking more kratom servings with greater frequency and regularity were more likely than others with more varied use patterns to perceive kratom as "life-saving" but also as "habit-forming," indicating a complex relationship (Smith et al., 2024). However, many consumers, irrespective of use motivations, have reported perceiving kratom as more effective, tolerable, and with less severe side-effects or risks than FDA-approved medicines; kratom consumers also noted that products are accessible and affordable, and are preferred as "natural" and "dietary" approaches over conventional medicines for their lifestyle needs (DEA, 2016;Grundmann, 2017;Smith et al., 2022c;Grundmann et al., 2023;Smith et al., 2024). ...
... Reasons for kratom use as documented by self-report surveys and field studies of kratom users (e.g., Singh et al., 2015;Grundmann, 2017) are often taken as proxies for therapeutic usefulness (e.g., Grundmann et al., 2018;Prozialeck et al., 2019). However, it is important to note that the FDA generally reserves the terms "therapeutic" "beneficial," and "medical" use for FDAapproved drugs, not for dietary ingredients or supplements for which only limited health-related (but not "therapeutic") claims can be made (FDA, 2005). ...
Article
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Although kratom use has been part of life for centuries in Southeast Asia, the availability and use of kratom in the United States (US) increased substantially since the early 2000s when there was little information on kratom pharmacology, use patterns, and effects, all critical to guiding regulation and policy. Here we provide a synthesis of research with several hundred English-language papers published in the past 5 years drawing from basic research, epidemiological and surveillance data, and recent clinical research. This review of available literature aims to provide an integrated update regarding our current understanding of kratom’s benefits, risks, pharmacology, and epidemiology, which may inform United States-based kratom regulation. Recent surveillance indicates there are likely several million past-year kratom consumers, though estimates vary widely. Even without precise prevalence data, kratom use is no longer a niche, with millions of United States adults using it for myriad reasons. Despite its botanical origins in the coffee tree family and its polypharmacy, kratom is popularly characterized as an opioid with presumed opioid-system-based risks for addiction or overdose. Neuropharmacology, toxicology, and epidemiology studies show that kratom is more accurately characterized as a substance with diverse and complex pharmacology. Taken together the work reviewed here provides a foundation for future scientific studies, as well as a guide for ongoing efforts to regulate kratom. This work also informs much-needed federal oversight, including by the United States Food and Drug Administration. We conclude with recommendations for kratom regulation and research priorities needed to address current policy and knowledge gaps around this increasingly used botanical product.
... Since 2015, there has been a dramatic increase in interest, importation, and use of kratom (Mitragyna speciosa Korth) leaf products in the United States (US; Grundmann, 2017). Various epidemiological studies estimate the lifetime use of kratom among the general American population to range from 0.9% to 6.1% (Covvey et al., 2020;Lee et al., 2022;Xu et al., 2021). ...
... Exploratory surveys seeking to better understand kratom use, motivations, and effects have found that many admit to using kratom to "self-manage" chronic pain, fatigue, symptoms of substance use disorders (opioid-withdrawal and/or as a replacement for full opioid agonists), as well as psychiatric conditions (Bath et al., 2020;Garcia-Romeu et al., 2020;Grundmann, 2017;Swogger & Walsh, 2018). Specifically, 58% to 67% of kratom users admit to using in attempts to self-manage depressive symptoms and other mental health concerns (Coe et al., 2019). ...
... The average age of kratom users in this study was 32.46 years of age. These characteristics align with what was reported in previous surveys of non-SMI individuals (Grundmann, 2017;Palamar, 2021). Although the gender distribution in prior surveys in Southeast Asia as well as the US (Covvey et al., 2020;Garcia-Romeu et al., 2020;Grundmann, 2017;Palamar, 2021;Prozialeck et al., 2019;Schimmel et al., 2021) was weighed more heavily toward males, this predominance was not reflected in our study; however, this may be due to the small sample size. ...
... The studies selected for review included 10 in vitro and animal studies, 20 studies with human subjects, and 16 case reports. The sample size of the 20 studies in human subjects varied from being as low as 30 subjects to as high as 32,893 subjects (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). No clinical trial was found from the database search. ...
... Five cross-sectional surveys were conducted to investigate the therapeutic potentials of kratom in the US population, and highlighted the respondents' subjective accounts, describing the effectiveness of kratom as a form of self-prescribed replacement therapy for prescribed opioid or illicit opioid use (18,(27)(28)(29)31). Around 10-66% of American respondents in these surveys agreed that kratom use alleviated opioid withdrawal, reduced prescribed and illicit opioid use, relieved pain related to opioid use, and allowed abstinence from opioid use for more than one year (18,27,28). ...
... Five cross-sectional surveys were conducted to investigate the therapeutic potentials of kratom in the US population, and highlighted the respondents' subjective accounts, describing the effectiveness of kratom as a form of self-prescribed replacement therapy for prescribed opioid or illicit opioid use (18,(27)(28)(29)31). Around 10-66% of American respondents in these surveys agreed that kratom use alleviated opioid withdrawal, reduced prescribed and illicit opioid use, relieved pain related to opioid use, and allowed abstinence from opioid use for more than one year (18,27,28). However, kratom use as an acute, self-prescribed treatment for opioid withdrawal is more prevalent than kratom use for longterm replacement therapy for opioid use disorder (29). ...
Article
Aims: This review aimed to comprehensively examine kratom’s therapeutic potential for treatment of mental health-related issues as well as any related benefits and risks. Design: Systematic review. Data sources: Google Scholar, Web of Science, PubMed, Scopus, PsycINFO, EMBASE, Cochrane Library, and Medline. Review methods: Three authors carried out electronic search of articles published between 1950 to September 2022 through major databases for a duration of three months (from July to September 2022). Each author independently screened the literature for inclusion and exclusion criteria, the findings were then compared, discrepancies between authors were resolved, and the final selection of articles were reviewed. Results: A total of 46 articles were included in this review. A total of three in vitro and animal studies and five cross-sectional online surveys reported the therapeutic potential of kratom in opioid replacement therapy. In addition, a total of two animal studies and three cross-sectional online surveys highlighted the role of kratom as a potential antidepressant and anxiolytic. Contrastingly, two animal studies, 11 studies in human subjects, and 16 case reports documented the risk of kratom dependence, cravings, tolerance, and kratom-related substance use disorder as the major safety concern of implementing kratom use as a therapeutic agent. Conclusion and impact: In the absence of human clinical trial, coupled with various considerable adverse events of kratom (not limited to psychological side effects), evidence to support kratom as potential therapeutic use remains inconclusive.
... These products are not currently regulated by the US Food and Drug Administration (U.S. Food and Drug Administration, 2024) and are the focus of intense debate. Surveys of consumers in the US suggest that kratom use can increase perceived quality of life, either by seeming to alleviate specific physical or psychological problems or by seeming to increase energy and productivity (Grundmann, 2017;Smith et al., 2021a;Smith et al., 2022b;Smith et al., 2022d). While kratom has only recently proliferated in the US, rural populations in Southeast Asia have historically used kratom as a remedy for common ailments, to ameliorate fatigue, and as an adjunct to social and religious events (Singh et al., 2017). ...
... We extended prior findings that kratom use can be primarily motivated by "self-treatment" for physical, psychiatric, and addiction-related symptoms (Grundmann, 2017;Swogger and Walsh, 2018;Garcia-Romeu et al., 2020). A departure from prior findings was greater prominence of recreational use, which had not been well characterized (Smith and Lawson, 2017;Coe et al., 2019;Smith et al., 2022c). ...
Article
Full-text available
Background “Kratom” refers to an array of bioactive products derived from Mitragyna speciosa, a tree indigenous to Southeast Asia. Most kratom consumers report analgesic and stimulatory effects, and common reasons for use are to address mental and physical health needs, manage pain, and to reduce use of other substances. Natural-history studies and survey studies suggest that many kratom consumers perceive benefits from those uses, but such studies are unlikely to capture the full range of kratom-use experiences. Methods We collected text data from Reddit posts from 2020-2022 to qualitatively examine conceptualizations, motivations, effects, and consequences associated with kratom use among people posting to social media. Reddit posts mentioning kratom were studied using template thematic analysis, which included collecting descriptions of kratom product types and use practices. Network analyses of coded themes was performed to examine independent relationships among themes, and between themes and product types. Results Codes were applied to 329 of the 370 posts that comprised the final sample; 134 posts contained kratom product descriptions. As Reddit accounts were functionally anonymous, demographic estimates were untenable. Themes included kratom physical dependence (tolerance, withdrawal, or use to avoid withdrawal), perceived addiction (net detrimental effects on functioning), and quitting. Extract products were positively associated with reports of perceived addiction, dependence, and experiences of quitting kratom. Many used kratom for energy and self-treatment of pain, fatigue, and problems associated with opioid and alcohol; they perceived these uses as effective. Consumers expressed frustrations about product inconsistencies and lack of product information. Conclusion As in previous studies, kratom was deemed helpful for some and a hindrance to others, but we also found evidence of notable negative experiences with kratom products that have not been well documented in surveys. Daily kratom use may produce mild-moderate physical dependence, with greater severity being possibly more common with concentrated extracts; however, there are currently no human laboratory studies of concentrated kratom extracts. Such studies, and detailed kratom product information, are needed to help inform consumer decision-making.
... U.S. kratom consumption has increased over the past two decades, with lifetime and past-year use estimates ranging from 0.5-6.1% and 0.7-4.1% of the population, respectively, with a higher prevalence among SUD populations (past-year and lifetime use: 10 and 21%, respectively) (4)(5)(6)(7)(8)(9). Kratom user demographics skew toward employed White males in their late teens to middle-age adults, with at least some college education (6,10,11). ...
... However, several concerns regarding kratom use warrant additional research before it can be recommended in clinical practice. Though generally tolerated at low and slowly titrated doses, kratom can produce adverse effects in line with their mild opioid and stimulant effects, including nausea, somnolence, confusion, agitation, hypertension, and tachycardia that are generally mild (10,19). Case reports describe more serious, rare adverse events, including seizures, hepatotoxicity, cardiac arrest, or overdose (13,20,21). ...
Article
Full-text available
Substance use disorders contribute to considerable U.S. morbidity and mortality. While effective pharmacotherapy options are available to treat opioid and alcohol use disorders, for a variety of reasons, many patients lack access to treatment or may be reluctant to seek care due to concerns such as perceived stigma or a current lack of desire to completely curtail their substance use. Furthermore, treatment options are limited for patients with stimulant or polysubstance use disorders. Thus, there is considerable need to expand the substance use disorder harm reduction armamentarium. Kratom (Mitragyna speciosa Korth.) is an herbal substance that can produce both opioid and stimulant-like effects, and its use in the US is growing. Though there are concerns regarding adverse effects, dependence risk, and limited regulation of its manufacturing and sale, the pharmacology of kratom and early preclinical studies suggest a potential role as a harm reduction agent for various substance use disorders, and it has historically been used in Southeast Asia for such purposes. The goal of this review is to describe kratom’s history of use, pharmacology, and early pre-clinical and observational research regarding its therapeutic potential in opioid use disorder, as well as alcohol, stimulant, and polysubstance use disorders, while also highlighting current concerns around its use, existing gaps in the literature, and directions for future research.
... We did not ask about the nature of said question, and whether it related to kratom's putative benefits, toxicities, or potential to produce physical dependence and withdrawal. Although kratom has been touted as a less addictive alternative to prescription opioids and illicit opioids (i.e., heroin), there is a growing body of evidence that regular kratom use can result in both physical and psychological dependence and addiction [37,38]. Several studies in rodents reported that abrupt cessation of MG can produce withdrawal symptoms within 24 h of the last dose [39][40][41]. ...
... Most kratom users in the U.S. are male (56.9%) and between the ages of 31 and 50 years [38]. Interestingly, among our survey respondents, male pharmacists were significantly more likely to have heard of kratom (p = 0.0015). ...
Article
Full-text available
Kratom (Mitragyna speciosa) is a botanical substance whose leaves produce stimulant- and opioid-like effects. Kratom use has increased precipitously in the United States (U.S.) over the last decade, yet, in our experience, many pharmacists are unfamiliar with this herb. The purpose of this study was to assess pharmacists’ awareness and knowledge of kratom. This cross-sectional study used an online questionnaire to preferentially solicit community pharmacists’ knowledge of kratom and collect demographic information. The survey was sent via email to approximately 10,000 pharmacists, targeting those in the state of Alabama, U.S. Data were analyzed using descriptive statistics, and the Chi Square test was used to compare nominal data. A total of 257 participants responded to the survey. Almost 50% of participants had heard of kratom, and 50% had not. Compared to females, males were more likely to have heard of kratom (64% vs. 42%; p = 0.0015), as were pharmacists who worked for an independent pharmacy vs. a chain (61% vs. 41%; p = 0.025). Of the participants who had heard of kratom, only 14% considered themselves knowledgeable or very knowledgeable about the herb, and only 44% knew it was illegal in Alabama. These data indicate a need to further kratom education among community pharmacists in Alabama.
... Kratom products are being increasingly used for the self-management of chronic pain, psychiatric conditions, as well as, as an opioid substitute for the management of opioid withdrawal. [1][2][3] The estimated lifetime prevalence in the United States (US) ranges between 0.9% and 6.1% with higher penetrance among those with concurrent psychiatric and substance userelated conditions. [3][4][5][6] The US Food and Drug Administration (FDA) has regulated kratom as a dietary supplement and has not approved any medical uses; however, more recently, following a significant increase in kratom-related calls to poison control centers, the FDA has been warning consumers about possible risks associated with its use. ...
... [3][4][5][6] The US Food and Drug Administration (FDA) has regulated kratom as a dietary supplement and has not approved any medical uses; however, more recently, following a significant increase in kratom-related calls to poison control centers, the FDA has been warning consumers about possible risks associated with its use. 1,4 Kratom contains over 40 alkaloids with both stimulant and opioid-like effects. 4,5,7 Mitragynine (MG) and 7-hydroxymitragynine (7-HMG) are the two main psychoactive alkaloids and mediate the pharmacological effects of kratom. ...
... Further, no significant adverse events were described and only mild, transient side effects (e.g., dizziness, headache, sleepiness) were reported from participants which were related to the highest (40 mg) dose of mitragynine. In the literature (Cinosi et al. 2015;Grundmann 2017;Grundmann et al. 2023;Kruegel and Grundmann 2018), these adverse events have been reported and are often linked to chronic use. However, they did not have any clinical relevance and resolved spontaneously without treatment. ...
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Rationale Despite the growing scientific interest on mitragynine, the primary alkaloid in kratom (Mitragyna Speciosa), there is a lack of clinical trials in humans. Objectives This phase 1 study aimed to evaluate mitragynine’s safety profile and acute effects on subjective drug experience, neurocognition, and pain tolerance. Methods A placebo-controlled, single-blind, within-subjects study was conducted in two parts. In part A, eight healthy human volunteers received placebo and three doses of mitragynine (5, 10, and 20 mg) in a sequential dosing scheme, on separate days. In part B, a second group of seven volunteers received placebo and 40 mg of mitragynine. Vital signs, subjective drug experience, neurocognitive function, and pain tolerance were measured at regular intervals for 7 h after administration. Results Overall, mitragynine did not affect most of the outcome measures at any dose. Yet, the lowest dose (5 mg) of mitragynine increased subjective ratings of arousal and attention, accuracy in a sustained attention task, and motor inhibition. The highest dose (40 mg) of mitragynine increased subjective ratings of amnesia and produced mild psychopathological symptoms. Mitragynine did not significantly affect vital signs, and only mild, transient side effects were reported. Conclusion The present study suggests that low doses (5–10 mg) of mitragynine may cause subjective feelings of stimulation and enhance attention, while the highest dose (40 mg) may cause inhibitory feelings of amnesia and distress. Mitragynine doses up to 40 mg were well tolerated in this group.
... 11 People use kratom for self-treatment of pain and to improve endurance or as an alternative for opioid use and mitigation for substance withdrawal. [11][12][13] However, the US Drug Enforcement Administration listed kratom as a drug of concern, 14 with increasing reports of kratom-involved deaths, [15][16][17] which is an emerging public health concern. Kratom is banned in 15 countries and 6 states in the United States: Alabama, Arkansas, Florida, Indiana, Tennessee, and Wisconsin. ...
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Introduction The US age-adjusted drug overdose rate increased by 298%, with fentanyl being the main contributor to drug overdose deaths. The contribution of kratom to drug overdoses or intoxication is seldom reported despite its increasing use and detection among overdose decedents. Methods Our cross-sectional study utilized deidentified data from the Florida Department of Law Enforcement, 2020–2021 (N = 30,845). The medical examiners ascertained the exposures of interest (kratom, opioids, and other substances) and the outcome variable of drug intoxication–related mortality (DIRM) through autopsies and toxicology results. DIRM refers to any death from a substance identified as drug toxicity or intoxication. We used regression modeling to examine the association of exposure with DIRM. Results Five hundred fifty-one cases were confirmed kratom (mitragynine) exposures. More males died of DIRM (81.5%), primarily White (95.1%) and 35–44 years old (40.5%). Among mitragynine exposures, 484 (87.8%) died of DIRM; 36 decedents (6.5%) used kratom as the sole substance, and 515 (93%) used multiple substances; 437 (79.3%) used at least 1 opioid. The odds of dying of DIRM were 7.6 times higher among those mitragynine exposed compared with non–mitragynine exposed (univariate model) and 5.6 times higher after adjusting for confounders (multivariate model) (adjusted odds ratio = 5.6; 95% confidence interval, 4.1–7; P < 0.001). Opioid use increased the odds of dying of DIRM (adjusted odds ratio = 11.7; 95% confidence interval, 10.9–12.7; P < 0.001). Conclusion Our results indicate that dozens of decedents died of kratom (mitragynine) exposures alone, which has safety implications. Co-using opioids with kratom further increased the odds of dying of DIRM, indicating that kratom may not always work as a harm-reduction agent.
... 5 US-based online surveys have consistently found that a widespread motivation for kratom use is chronic pain self-management. [9][10][11][12] Some preliminary evidence for kratom's analgesic effects were found in one placebo-controlled study conducted in Malaysia which demonstrated that kratom significantly enhanced cold pain tolerance in 26 healthy adult males who regularly consumed kratom. 13 These findings from self-report and lab-based studies likely reflect the activity of multiple alkaloids in kratom, specifically kratom's major alkaloid, mitragynine, and minor alkaloids, speciogynine, paynantheine, and speciociliatine, which have been shown in pre-clinical models to contribute to pain relief through opioidergic, serotonergic, and adrenergic mechanisms. ...
... Mitragyna speciosa ("kratom") is a tropical tree from Southeast Asia that has been used for centuries by local farmers to combat pain, fatigue and increase productivity (Cinosi et al., 2015). Kratom has since become popular in Western countries for the (self)treatment of pain, depression, and to alleviate opioid withdrawal symptoms (Grundmann, 2017). It is currently estimated that kratom is used by millions in the USA alone (Swogger et al., 2022). ...
... As such, the risk-benefit ratio of kratom is complicated. Kratom is also used nonmedically to attenuate withdrawal symptoms from opioids, stimulants and alcohol (13,14). One survey found that a majority (94.8%) of kratom consumers had abstained from other substance use for at least 6 months, highlighting kratom's role in nonmedically managing addiction (11, 12, 15, 16). ...
... [7] Mitragyna speciosa (Korth and Rubiaceae) or kratom is a native medicinal plant of Southeast Asia. [8] Although many large-scale surveys have reported kratom's beneficial effects in reducing pain and managing opioid dependence and physical withdrawal, [9][10][11] enforcement agencies and health-care providers continue to report the negative effects of kratom use. [12,13] This has led to the argument about kratom's potential benefits and its perceived risk of abuse. ...
... Kratom is currently legal in 45 US states and its use is increasing rapidly, but our understanding of its effects, including its impact on driving behavior, lags behind (Babu et al. 2008;Grundmann 2017;Swogger et al. 2015). To our knowledge, this study is the first to investigate the driving habits and behaviors of people who use kratom regularly. ...
Article
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.
... tree is a Southeast Asian tropical evergreen in the Rubiacaeae family related to the coffee tree [1]. The oral consumption of kratom leaves dates back hundreds of years in Southeast Asia, where the leaves are typically chewed fresh, brewed into a tea, or processed into tar-like extracts [2]. Millions consume kratom worldwide as food, dried leaf powders in capsules, concocted into beverages or teas, or as processed extracts [3][4][5]. ...
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Kratom leaves, consumed by millions worldwide as tea or ground leaf powder, contain multiple alkaloids, with mitragynine being the most abundant and responsible for most effects. Mitragynine is a partial µ-opioid receptor agonist and competitive antagonist at κ- and δ-opioid receptors; however, unlike morphine, it does not activate the β-arrestin-2 respiratory depression pathway. Due to few human mitragynine data, the largest randomized, between-subject, double-blind, placebo-controlled, dose-escalation study of 500–4000 mg dried kratom leaf powder (6.65–53.2 mg mitragynine) was conducted. LC-MS/MS mitragynine and 7-hydroxymitragynine plasma concentrations were obtained after single and 15 daily doses. Mitragynine and 7-hydroxymitragynine Cmax increased dose proportionally, and AUC was slightly more than dose proportional. The median mitragynine Tmax was 1.0–1.3 h after single and 1.0–1.7 h after multiple doses; for 7-hydroxymitragynine Tmax, it was 1.2–1.8 h and 1.3–2.0 h. Steady-state mitragynine concentrations were reached in 8–9 days and 7-hydroxymitragynine within 7 days. The highest mean mitragynine T1/2 was 43.4 h after one and 67.9 h after multiple doses, and, for 7-hydroxymitragynine, it was 4.7 and 24.7 h. The mean 7-hydroxy-mitragynine/mitragynine concentration ratios were 0.20–0.31 after a single dose and decreased (0.15–0.21) after multiple doses. These mitragynine and 7-hydroxymitragynine data provide guidance for future clinical kratom dosing studies and an interpretation of clinical and forensic mitragynine and 7-hydroxymitragynine concentrations.
... 56,57 Individuals with psychiatric conditions and polysubstance use must seek a healthcare provider's opinion before using kratom. 11,58 The index case illustrates the complexity involved in managing psychiatric manifestations in the presence of kratom use and the likelihood of experiencing withdrawal symptoms. The co-occurrence of psychiatric problems and withdrawal underscores the significance of an integrated approach in treating such cases. ...
Article
Objective This review aims to synthesize and critically evaluate the existing literature on kratom use and its possible association with induction of psychotic and manic symptoms, in order to identify potential areas for future research that would improve our understanding of the risks of kratom consumption. Methods An electronic search was performed using five major databases: including PubMed, Scopus, Google Scholar, Web of Science, and PsycINFO. keywords such as kratom, Mitragyna speciosa, mania, psychosis, bipolar disorder, schizophrenia, schizoaffective, case report, and case series. The retrieved articles on initial search were screened based on predefined inclusion and exclusion criteria for this study, and then data synthesis was performed to analyze relevant information from the included studies. Results Six prior papers were found using (1 case series and 5 case reports). These included 10 cases, involving kratom use association with mania and psychosis. The ages of patients ranged from 28 to 55 years mean age was 38, and (SD 13.74), the majority were males (8 out of 11). Patients had durations of kratom use ranging from 2 wk to 15 years. Significant association was found between kratom use and the worsening of psychotic and manic symptoms in individuals with psychiatric conditions. Conclusions Our research highlights the possibility of worsening preexisting psychiatric conditions in the context of kratom use. This study emphasizes the need for clinical evaluation of patients for kratom use. Additional research is required to gain a deeper understanding of the potential mental health implications of kratom use, especially among vulnerable populations.
... Many short-term and long-term users claimed to feel more energetic, capable of working hard, and to have a higher sexual desire [9,47]. Another anonymous cross-sectional online survey in the USA was carried out with 8049 kratom users in 2006 [48]. The results of this study showed that middle-aged (31-50 years) and middle-income (over $35,000) people are the main users of kratom, with the main uses being the treatment of pain (68%) and emotional or mental conditions (66%). ...
Article
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Kratom (Mitragyna speciosa Korth. Havil) has been considered a narcotic drug for years, barred by the law in many parts of the world, while extensive research over the past few decades proves its several beneficial effects, some of which are still in ambiguity. In many countries, including Thailand, the indiscriminate use and abuse of kratom have led to the loss of life. Nonetheless, researchers have isolated almost fifty pure compounds from kratom, most of which are alkaloids. The most prevalent compounds, mitragynine and 7-hydroxy mitragynine, are reported to display agonist morphine-like effects on human μ-opioid receptors and antagonists at κ- and δ-opioid receptors with multimodal effects at other central receptors. Mitragynine is also credited to be one of the modulatory molecules for the Keap1-Nrf2 pathway and SOD, CAT, GST, and associated genes’ upregulatory cascades, leading it to play a pivotal role in neuroprotective actions while evidently causing neuronal disorders at high doses. Additionally, its anti-inflammatory, antioxidative, antibacterial, and gastroprotective effects are well-cited. In this context, this review focuses on the research gap to resolve ambiguities about the neuronal effects of kratom and demonstrate its prospects as a therapeutic target for neurological disorders associated with other pharmacological effects.
... It is estimated that in the US alone, approximately 10-15 million people are using kratom (American Kratom Association 2019; Swogger et al. 2022) for recreational and therapeutic purposes. The latter includes self-medication for pain, conditions of mental distress, and substance use disorders (SUDs), mainly for opioid use (Bath et al. 2020;Coe et al. 2019;Grundmann 2017Grundmann , 2022Singh et al. 2017). ...
Article
Recently in the USA, kratom consumers increasingly report use of the plant for self-treatment of mood ailments, the lack of energy, chronic pain, and opioid withdrawal and dependence. Several alkaloids are present in kratom leaves, but limited data are available on their pharmacokinetics/pharmacodynamics, except for mitragynine. To support clinical studies, a high-performance liquid chromatography-tandem mass spectrometry assay for the simultaneous quantification of 11 kratom alkaloids in human plasma was developed and validated. For calibration standards and quality control samples, human plasma was fortified with alkaloids at varying concentrations, and 200 µL were extracted employing a simple one-step protein precipitation procedure. The extracts were analyzed using LC-MS/MS including electrospray ionization (ESI) in positive multiple reaction monitoring (MRM) mode. The lower limit of quantification was 0.5 ng/mL, and the upper limit of quantification was 400 ng/mL for all analytes. Inter-day analytical accuracy and imprecision ranged from 98.4 to 113% of nominal and from 3.9 to 14.7% (coefficient of variance), respectively. The analysis of plasma samples collected during a clinical trial administering capsules containing kratom leaf extract showed that most samples had quantifiable concentrations of mitragynine, 7-OH-mitragynine, speciogynine, speciociliatine, and paynantheine and that mitragynine, speciogynine, and speciociliatine accumulated in human plasma after daily administration over 15 days. An LC-MS/MS assay for the specific quantification of kratom alkaloids including mitragynine and its main metabolites was developed and successfully validated in human plasma. Human plasma samples collected following multiple oral administrations of a controlled Kratom extract documented accumulation of kratom alkaloids over 15 days.
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The term "kratom" refers to a plant species formally known as Mitragyna speciosa. Kratom is composed of over 40 alkaloids, a type of organic compound that contains nitrogen. These compounds work primarily via binding to opioid receptors expressed on neurons, where they stimulate signal transduction mechanisms involving the activation of G proteins. Kratom has been shown to cause both a stimulant-like effect and a sedative effect in humans. These studies have shown that use is highest among European-American, middle-class men living in suburban areas. Additionally, individuals who have a history of opioid misuse are also more likely to take kratom. Kratom is used by many different people in the US for numerous different reasons. Some of the most often cited reasons include treating chronic pain conditions, depression, and anxiety. Individuals who used kratom for these reasons typically consumed kratom daily at a dose of 1-3 grams, with the kratom extracted into a powder to be consumed in a capsule. Additionally, there have been reports of kratom being used to treat opioid withdrawal symptoms, as kratom can bind to some of the same receptors as opioids. This manuscript specifically describes trends regarding the use of kratom in the US, pharmacokinetic and pharmacodynamic properties of kratom, potential therapeutic uses of kratom, adverse events caused by kratom, and case studies in the literature regarding patients using kratom.
Chapter
In this alphabetically arranged chapter, supplements from hawthorn through lysine are discussed in detail. For each supplement, this chapter defines what it is and how it works in the body. Further, this chapter discusses the supplement’s recommended dosage as well as the evidence for or against its different usages. Safety concerns, side effects, and precautions are next discussed as well as any potential interactions with other medications. References are provided for the data provided. The goal is for the healthcare provider to be able to reference each supplement and come away with a full, balanced, evidence-based understanding of these topics
Article
Introduction: Kratom is commonly used by consumers, and the elemental impurity exposure that consumers would have at different kratom ingestion doses has been determined. Methods: This assessment used original data from independent third-party laboratory testing of kratom products to identify the percentage of products that exceeded permissible daily exposure limits for lead (5 µg/day), nickel (200 µg/day), arsenic (15 µg/day), and cadmium (5 µg/day), the interim reference level for lead in adults (12.5 µg/day), and the tolerable upper intake level for manganese (11 mg/day) and nickel (1 mg/day). We assessed all products regardless of type and then evaluated non-extract products, extract products, and a soda preparation separately for elemental impurities. Results: Three assessments of elemental impurities in kratom products have been published, totaling 68 products. Assessing all products and assuming a 3 g daily dose of kratom, 7.4% would exceed the permissible daily exposure limits for lead, 0% for nickel, 3.1% for arsenic, and 0% for cadmium. At a kratom dose of 25 g daily, 70.6% would exceed the permissible daily exposure limits for lead, 20.6% for nickel, 9.4% for arsenic, and 0% for cadmium. The interim reference level for lead would be exceeded by 1.5% of products at a kratom daily dose of 3 g and 33.8% of products at 25 g. The tolerable upper intake level for manganese would be exceeded by 12.5% of products at a kratom daily dose of 3 g and 41.7% of products at 25 g. Non-extract products generally contain greater concentrations of elemental impurities than extract products or the soda preparation. Discussion: Apart from their concentrations in a gram of product, assessing the amount of exposure to elemental impurities at different kratom ingestion doses is also important. Elemental impurities exceeding regulatory permissible concentrations for many products, especially with greater daily kratom ingestion doses, may impact human health. Conclusions: Some kratom products contain excessive concentrations of elemental impurities of toxicological concern, such as lead and arsenic. Non-extract products (powders, capsules, tablets) generally contain greater concentrations of elemental impurities than extract products or the soda preparation. Daily use of these products can result in exposures exceeding regulatory thresholds and adverse health effects.
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Traditionally used in Southeast Asia for common ailments, kratom (Mitragyna speciosa) is increasingly being adopted in other regions for the self-treatment of pain, mental health issues such as anxiety, depression, and dependence or managing the withdrawal symptoms linked to stimulants/sedatives or other substances in absence of clinical supervision. To gain better insight into the experiences and the motivations underlying kratom use, previous studies have analyzed material shared among users on social media. However, these investigations often employed manual labeling and categorizations, which are time-consuming and do not allow the investigation of large samples. The present work utilized a natural language processing approach (BERTopic) to extract prominent topics of discussion from kratom-related Reddit posts made between 2010 to 2023 (n = 188,139 posts). Dynamic Topic Modeling was also implemented to analyze how discussions about these topics evolved over time. From the results, users discussed topics including usage for substance use disorder recovery (e.g., suboxone), drug testing, consumption methods, logistic issues (e.g., bringing kratom on flights, receiving kratom via mail), tapering off the use of kratom, and providing support to others who are in the process of quitting kratom. The current study supports the need of clinical trials as well as new ecological insights into experiences of kratom users, while supporting the implementation of new policies to regulate its usage.
Article
Kratom/ketum is a psychoactive herbal preparation that has been used for a long time as a remedy and performance-enhancing substance in Southeast Asia. The advancement of globalization is making kratom increasingly more available in the western world, where it is becoming increasingly more used. The current research on kratom and its ingredients is presented. An overview of the use and effects of kratom is exemplary given on the basis of reports. The instrumentalization of the drug and its consequences up to the development of addiction are discussed. Consumption is accompanied by several instrumentalizeable effects so that kratom is used as a therapeutic substance in the self-management of pain, anxiety and depression as well as other substance addictions. Another benefit comes from the performance-enhancing effects on physical work and in a social context. Consumption is usually well controlled, rarely escalates and has few and mostly mild aversive side effects. The danger arises from consumption particularly when there is an escalation of the dose and from mixed consumption with other psychoactive substances. The main alkaloid mitragynine and the more potent 7‑hydroxy-mitragynine are considered mainly responsible for the effect. Both have a complex pharmacology that involves partial µ‑opioid receptor agonism. Epidemiological, clinical and neurochemical studies have shown that kratom only has a limited addictive drug profile, which might suggest a medical use as a remedy or substitute in addiction treatment.
Article
Objectives To estimate lifetime, past-year, and past-month prevalence of kratom, cannabis, and cannabidiol-only product use among adults 18 years and older in the United States, using 2 independent datasets. Methods Utilizing ( a ) the 2022 National Survey on Drug Use and Health (NSDUH) and ( b ) a 2022 online national convenience sample of adults who use kratom regularly (from our research group at the National Institute on Drug Abuse [NIDA]), we examined key demographic information as well as lifetime, past-year, and past-month substance use and preferences. Results Among the full sample of adults from the 2022 NSDUH, the prevalence of lifetime use was 49.69% for cannabis, 34.09% for cannabidiol-only products, and 1.93% for kratom. When solely examining participants who have used kratom, both independent datasets showed higher proportions of cannabis use over the lifetime—92.81% (95% confidence interval: 90.31–95.31) in the NSDUH subset and 92.16% (95% confidence interval: 89.37–94.95) in our NIDA sample. Conclusions Our study demonstrates that people are co-using kratom with cannabis and/or cannabidiol-only products at the same time or during the same time period, though more research is needed to understand people's motivations and practices for such co-use. Co-use might result in herb-herb interactions that may impact research findings and clinical outcomes for people who use kratom.
Article
Purpose of review Kratom is used commonly in the United States, usually to mitigate pain, opioid withdrawal, or fatigue. A comprehensive discussion on kratom, tailored to pain management physicians, is needed, given its associated risks and potential interactions. Recent findings Kratom and its main metabolites, mitragynine and 7-OH-mitragynine, bind to a variety of receptors including mu opioid receptors. Still, kratom cannot be described as a classic opioid. Kratom has been utilized without FDA approval as an alternative to traditional medications for opioid use disorder and opioid withdrawal. Lower doses of kratom typically cause opioid-like effects while higher doses can have sedating effects. Tolerance, dependence and withdrawal still occur, although kratom withdrawal appears to be more moderate than opioid withdrawal. Contamination with heavy metals and biological toxins is concerning and there is potential for serious complications, including seizures and death. Summary The use of kratom as an opioid-sparing alternative as a part of a multimodal pain regimen is not without significant risks. It is of utmost importance for pain physicians to be aware of the risks and adverse effects associated with kratom use.
Article
Introduction: Kratom (Mitragyna speciosa) is a medicinal tree native to Southeast Asia. The present multilevel meta-analysis describes the association between kratom use and the positive and negative indicators of mental health. Methods: A total of thirty-six articles were included in the meta-analysis to examine the associations, using a random-effects model. Results: The pooled effect size showed a very small positive association between kratom use and negative indicators of mental health {r = 0.092, 95% confidence interval (CI) = [0.020, 0.164], p < 0.05}, while no significant association was found with positive indicators of mental health (r = -0.031, 95% CI = [-0.149, 0.087], p > 0.05). Pooled effect sizes of specific mental health outcomes indicated that kratom use showed only a small positive correlation with externalizing disorders (r = 0.201, 95% CI = [0.107, 0.300], p < 0.001). No significant association was found between kratom use and quality of life (r = 0.069, 95% CI = [-0.104, 0.242], p > 0.05) and internalizing disorders (r = -0.001, 95% CI = [-0.115, 0.095], p > 0.05). Multilevel moderator analysis showed that the pooled effect size of the association between kratom use and substance use disorder was stronger in Malaysia (r = 0.347, 95% CI = [0.209, 0.516], p < 0.001), and with the mean age (β1 = -0.035, 95% CI = [-0.055, -0.014], p = 0.003), and the drug profile of those who were not co-using other drugs (r = 0.347, 95% CI = [0.209, 0.516], p < 0.001). Conclusion: The meta-analysis supports the kratom instrumentalization concept, in that a positive gain from kratom consumption can be achieved without any significant adverse associations with mental health.
Article
Kratom (Mitragyna speciosa) is a substance derived from botanical compounds native to Southeast Asia. This substance has been cultivated predominantly in Thailand, Malaysia, Vietnam, and Myanmar, where it has historically been used in traditional medicine as a near panacea for several health problems. Such ritualistic use of kratom has been present for centuries; however, recreational use appears to have increased globally, especially in the United States. Pharmacodynamic and pharmacokinetic studies have found that kratom demonstrates a unique parabolic, dose-dependent pattern of effects ranging from stimulation to opioid and analgesic effects. Pharmacological research indicates that kratom is both a mu opioid receptor (μ-OR; MOR) and a kappa opioid receptor (κ-OR; KOR) agonist, which mediates its analgesic effects. Other research suggests that kratom may simultaneously act on dopaminergic and serotonergic receptors, which mediate its stimulant effects. This chapter reviews the literature related to the structural, functional, and cultural characteristics of kratom use. We begin with an overview of current and historical patterns of kratom, followed by a review of data on the pharmacodynamics and pharmacokinetics of kratom thus far.
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Monoterpene indole alkaloids (MIAs) from Mitragyna speciosa (“kratom”), such as mitragynine and speciogynine, are promising novel scaffolds for opioid receptor ligands for treatment of pain, addiction, and depression. While kratom leaves have been used for centuries in South-East Asia as stimulant and pain management substance, the biosynthetic pathway of these psychoactives have only recently been partially elucidated. Here, we demonstrate the de novo production of mitragynine and speciogynine in Saccharomyces cerevisiae through the reconstruction of a five-step synthetic pathway from common MIA precursor strictosidine comprising fungal tryptamine 4-monooxygenase to bypass an unknown kratom hydroxylase. Upon optimizing cultivation conditions, a titer of ∼290 µg/L kratom MIAs from glucose was achieved. Untargeted metabolomics analysis of lead production strains led to the identification of numerous shunt products derived from the activity of strictosidine synthase (STR) and dihydrocorynantheine synthase (DCS), highlighting them as candidates for enzyme engineering to further improve kratom MIAs production in yeast. Finally, by feeding fluorinated tryptamine and expressing a human tailoring enzyme, we further demonstrate production of fluorinated and hydroxylated mitragynine derivatives with potential applications in drug discovery campaigns. Altogether, this study introduces a yeast cell factory platform for the biomanufacturing of complex natural and new-to-nature kratom MIAs derivatives with therapeutic potential.
Article
Mitragyna speciosa, also known as Kratom, is an evergreen tree native to Southeast Asia that has been used in traditional medicine to relieve pain. The primary active alkaloid, mitragynine, found in Kratom leaves affects the same µ-receptor as the opioids. The potential effects of Kratom leaves on humans draw international concerns. The purpose of this study is to develop an efficient extraction method for mitragynine from dried Kratom leaves. Mitragynine was extracted from grounded Kratom leaves by liquid-liquid extraction and detected by an HPLC system with a C-18 column. The extracted sample was eluted with a mobile phase of 0.05% formic acid and acetonitrile (50:50, v/v), flow rate = 1.0 mL/min. Mitragynine was detected at 223 nm. The amount of mitragynine in four different strains of Kratom leaves was determined (wt/wt). Intra-day (n = 3) and inter-day(n = 3) studies show excellent precision with RSD < 2.1% and RSD < 3.6% respectively.
Article
Objectives Kratom leaf products are increasingly consumed in the United States, with many consumers reporting they experience beneficial effects from kratom use. However, there is a growing concern for kratom’s potential to result in dependence when used regularly. As such, we sought to assess, using Diagnostic and Statistical Manual of Mental Disorders , (DSM-5) , diagnostic criteria for substance use disorder, the prevalence of “kratom use disorder” (KUD) among kratom consumers. Methods Our cross-sectional study used an online, anonymous survey between February and May 2023. Through nonprobability sampling, we recruited people older than 18 years who currently consume kratom. Participants were asked about their kratom consumption patterns, adverse effects perceived to stem from kratom consumption, comorbid diagnoses, and components for a DSM-5 , substance use disorder, adapted for kratom. Results Among the total sample ( N = 2061), KUD criteria were met by 25.5% of participants ( n = 525); the most commonly reported symptoms were tolerance ( n = 427, 81.3%) and withdrawal ( n = 357, 68.0%). After adjusting for age, gender, daily frequency of kratom consumption, and history of either a substance use disorder or a mental health condition, those with a concurrent diagnosis of another substance use disorder had 2.83 times higher odds of meeting KUD criteria (95% CI, 2.19–3.67) compared with those without one. Conclusions In this large cross-sectional study, most participants who met the criteria for a KUD diagnosis were categorized as having a mild or moderate KUD. Individual characteristics associated with KUD were related to being male, young, consuming kratom frequently, and having psychiatric and substance use disorder comorbidities.
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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.
Introduction: Kratom (Mitragyna speciosa) has generated substantial clinical and scientific interest as a complex natural product. Its predominant alkaloid mitragynine and several stereoisomers have been studied for activity in opioid, adrenergic, and serotonin receptors. While awaiting clinical trial results, the pre-clinical evidence suggests a range of potential therapeutic applications for kratom with careful consideration of potential adverse effects. Areas covered: The focus of this review is on the pharmacology, pharmacokinetics, and potential drug-drug interactions of kratom and its individual alkaloids. A discussion on the clinical pharmacology and toxicology of kratom is followed by a summary of user surveys and the evolving concepts of tolerance, dependence, and withdrawal associated with kratom use disorder. Expert opinion: With the increasing use of kratom in clinical practice, clinicians should be aware of the potential benefits and adverse effects associated with kratom. While many patients may benefit from kratom use with few or no reported adverse effects, escalating dose and increased use frequency raise the risk for toxic events in the setting of polysubstance use or development of a use disorder.
Article
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.
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Mitragyna speciosa (Rubiaceae), commonly known as kratom, is a tropical tree with a long history of traditional use in parts of Africa and Southeast Asia. In recent years, kratom has gained popularity for use as a recreational drug across the globe. Relatively new to the illicit market and used in a manner different from its traditional applications, preparations of kratom are touted by many as a safe and legal psychoactive product that improves mood, relieves pain, and may provide benefits in opiate addiction. Available literature was reviewed for M. speciosa via PubMed, Google Scholar, CINAHL, and EBSCO to summarize its traditional uses, phytochemical composition, pharmacology and toxicology of proposed active constituents, and potential for misuse and abuse. Research has demonstrated that both stimulant and sedative dose-dependent effects do exist, but a growing concern for the drug's effects and safety of use has resulted in national and international attention primarily due to an increase in hospital visits and deaths in several countries that are said to have been caused by extracts of the plant. The main active alkaloid substances in kratom, mitragynine and 7-hydroxymitragynine, present with a range of CNS stimulant and depressant effects mediated primarily through monoaminergic and opioid receptors. Recently, Palm Beach County, located in the southeastern corridor of Florida, has considered regulating kratom due to public safety concerns following the death of a young adult. At the local, state, and even federal levels, governments are now being confronted with the task of determining the safety and the possible regulation of kratom extracts. There are currently no standard analytical screening techniques for mitragynine and its metabolites following ingestion limiting its detection to more sophisticated techniques like liquid chromatography-mass spectrometry to determine kratom use. The growing concern of the abuse potential of kratom requires careful evaluation of its benefits and potential toxicities.
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Background E-cigarettes may be effective smoking cessation aids and their use by smokers has been growing rapidly. It is important to observe and assess natural patterns in the use of e-cigarettes while experimental data accumulates. This paper reports the prevalence of e-cigarette awareness, beliefs and usage, including brand choice, and characterises the socio-demographic and smoking profile associated with current use, among the general population of smokers and recent ex-smokers. Methods Data were obtained from 3538 current and 579 recent ex-smokers in a cross-sectional online survey of a national sample of smokers in Great Britain in December 2012. Differences between current and recent ex-smokers in the prevalence of e-cigarette awareness, beliefs and usage were examined and the socio-demographic and smoking profile associated with current use of e-cigarettes was assessed in a series of simple and multiple logistic regressions. Results Ninety-three per cent of current and recent ex-smokers (n = 3841) were aware of e-cigarettes. Approximately a fifth (n = 884) were currently using e-cigarettes, while just over a third (n = 1507) had ever used them. Sixty-seven per cent of the sample (n = 2758) believed e-cigarettes to be less harmful than cigarettes; however, almost a quarter (n = 994) remained unsure. Among both current and recent ex-smokers, the most popular reasons for using were health, cutting down and quitting (each > 80%) and 38% used the brand ‘E-lites’. Among current smokers who were aware of but had never used e-cigarettes, approximately half (n = 1040) were interested in using them in the future. Among current smokers, use was associated with higher socio-economic status (OR = 0.68, 95%CI = 0.57-0.80), smoking more cigarettes (OR = 1.02, 95%CI = 1.01-1.03) and having a past-year quit attempt (OR = 2.82, 95%CI = 2.38-3.34). Conclusions There is a near universal awareness of e-cigarettes and use appears to be common among smokers in Great Britain although a quarter of all smokers are unsure as to whether e-cigarettes are less harmful than cigarettes. E-lites – a brand that delivers a low dose of nicotine – is the most popular. E-cigarette users appear to have higher socio-economic status, to smoke more cigarettes per day and to have attempted to quit in the past year.
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Kratom (or Ketum) is a psychoactive plant preparation used in Southeast Asia. It is derived from the plant Mitragyna speciosa Korth. Kratom as well as its main alkaloid, mitragynine, currently spreads around the world. Thus, addiction potential and adverse health consequences are becoming an important issue for health authorities. Here we reviewed the available evidence and identified future research needs. It was found that mitragynine and M. speciosa preparations are systematically consumed with rather well defined instrumentalization goals, e.g. to enhance tolerance for hard work or as a substitute in the self-treatment of opiate addiction. There is also evidence from experimental animal models supporting analgesic, muscle relaxant, anti-inflammatory as well as strong anorectic effects. In humans, regular consumption may escalate, lead to tolerance and may yield aversive withdrawal effects. Mitragynine and its derivatives actions in the central nervous system involve μ-opioid receptors, neuronal Ca2+ channels and descending monoaminergic projections. Altogether, available data currently suggest both, a therapeutic as well as an abuse potential.
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Kratom (Mitragyna speciosa) is a plant indigenous to Thailand and Southeast Asia. Kratom leaves produce complex stimulant and opioid-like analgesic effects. In Asia, kratom has been used to stave off fatigue and to manage pain, diarrhea, cough, and opioid withdrawal. Recently, kratom has become widely available in the United States and Europe by means of smoke shops and the Internet. Analyses of the medical literature and select Internet sites indicate that individuals in the United States are increasingly using kratom for the self-management of pain and opioid withdrawal. Kratom contains pharmacologically active constituents, most notably mitragynine and 7-hydroxymitragynine. Kratom is illegal in many countries. Although it is still legal in the United States, the US Drug Enforcement Administration has placed kratom on its "Drugs and Chemicals of Concern" list. Physicians should be aware of the availability, user habits, and health effects of kratom. Further research on the therapeutic uses, toxic effects, and abuse potential of kratom and its constituent compounds are needed.
Article
Kratom (Mitragyna speciosa) is a plant consumed throughout the world for its stimulant effects and as an opioid substitute (1). It is typically brewed into a tea, chewed, smoked, or ingested in capsules (2). It is also known as Thang, Kakuam, Thom, Ketum, and Biak (3). The Drug Enforcement Administration includes kratom on its Drugs of Concern list (substances that are not currently regulated by the Controlled Substances Act, but that pose risks to persons who abuse them), and the National Institute of Drug Abuse has identified kratom as an emerging drug of abuse (3,4). Published case reports have associated kratom exposure with psychosis, seizures, and deaths (5,6). Because deaths have been attributed to kratom in the United States (7), some jurisdictions have passed or are considering legislation to make kratom use a felony (8). CDC characterized kratom exposures that were reported to poison centers and uploaded to the National Poison Data System (NPDS) during January 2010-December 2015. The NPDS is a national database of information logged by the country's regional poison centers serving all 50 United States, the District of Columbia, and Puerto Rico and is maintained by the American Association of Poison Control Centers. NPDS case records are the result of call reports made by the public and health care providers.
Article
Mu-opioid receptor agonists represent mainstays of pain management. However, the therapeutic use of these agents is associated with serious side effects, including potentially lethal respiratory depression. Accordingly, there is a longstanding interest in the development of new opioid analgesics with improved therapeutic profiles. The alkaloids of the Southeast Asian plant Mitragyna speciosa, represented by the prototypical member mitragynine, are an unusual class of opioid receptor modulators with distinct pharmacological properties. Here we describe the first receptor-level functional characterization of mitragynine and related natural alkaloids at the human mu-, kappa-, and delta-opioid receptors. These results show that mitragynine and the oxidized analogue 7-hydroxymitragynine, are partial agonists of the human mu-opioid receptor and competitive antagonists at the kappa- and delta-opioid receptors. We also show that mitragynine and 7-hydroxymitragynine are G-protein-biased agonists of the mu-opioid receptor, which do not recruit β-arrestin following receptor activation. Therefore, the Mitragyna alkaloid scaffold represents a novel framework for the development of functionally biased opioid modulators, which may exhibit improved therapeutic profiles. Also presented is an enantioselective total synthesis of both (-)-mitragynine and its unnatural enantiomer, (+)-mitragynine, employing a proline-catalyzed Mannich-Michael reaction sequence as the key transformation. Pharmacological evaluation of (+)-mitragynine revealed its much weaker opioid activity. Likewise, the intermediates and chemical transformations developed in the total synthesis allowed the elucidation of previously unexplored structure-activity relationships (SAR) within the Mitragyna scaffold. Molecular docking studies, in combination with the observed chemical SAR, suggest that Mitragyna alkaloids adopt a binding pose at the mu-opioid receptor that is distinct from that of classical opioids.
Article
The effects of mitragynine on anxiety-related behaviours in the open-field and elevated plus-maze tests were evaluated. Male Sprague-Dawley rats were orally treated with mitragynine (10, 20 and 40 mg/kg) or diazepam (10 mg/kg) 60 min before behavioural testing. Mitragynine doses used in this study were selected on the basis of approximately human equivalent doses with reference to our previous literature reports. Acute administration of mitragynine (10, 20 and 40 mg/kg) or diazepam (10 mg/kg) increased central zone and open arms exploration in the open-field and elevated plus-maze tests respectively. These anxiolytic-like effects of mitragynine were effectively antagonized by intraperitoneal administration of naloxone (2 mg/kg), flumazenil (10 mg/kg), sulpiride (0.5 mg/kg) or SCH 23390 (0.02 mg/kg) 15 min before mitragynine treatments. These findings reveal that the acute administration of mitragynine produces anxiolytic-like effects and this could be possibly attributed to the interactions among opioidergic, GABAergic and dopaminergic systems in brain regions involved in anxiety.
Article
This study was conducted to compare safety and efficacy outcomes between opioids formulated with technologies designed to deter or resist tampering (i.e., abuse-deterrent formulations [ADFs]) and non-ADFs for commonly prescribed opioids for treatment of non-cancer pain in adults. PubMed and Cochrane Library databases were searched for opioid publications between September 1, 2001 and August 31, 2011, and pivotal clinical trials from all years; abstracts from key pain conferences (2010-2011) were also reviewed. One hundred and ninety-one publications were initially identified, 68 of which met eligibility criteria and were systematically reviewed; a subset of 16 involved a placebo group (13 non-ADFs vs placebo, 3 ADFs vs placebo) and reported both efficacy and safety outcomes, and were included for a meta-analysis. Summary estimates of standardized difference in mean change of pain intensity (DMCPI), standardized difference in sum of pain intensity difference (DSPID), and odds ratios (ORs) of each adverse event (AE) were computed through random-effects estimates for ADFs (and non-ADFs) vs placebo. Indirect treatment comparisons were conducted to compare ADFs and non-ADFs. Summary estimates for standardized DMCPI and for standardized DSPID indicated that ADFs and non-ADFs showed significantly greater efficacy than placebo in reducing pain intensity. Indirect analyses assessing the efficacy outcomes between ADFs and non-ADFs indicated that they were not significantly different (standardized DMCPI [0.39 {95% confidence interval (CI) 0.00-0.76}]; standardized DSPID [-0.22 {95% CI -0.74 to 0.30}]). ADFs and non-ADFs both were associated with higher odds of AEs than placebo. Odds ratios from indirect analyses comparing AEs for ADFs vs non-ADFs were not significant (nausea, 0.87 [0.24-3.12]; vomiting, 1.54 [0.40-5.97]; dizziness/vertigo, 0.61 [0.21-1.76]; headache, 1.42 [0.57-3.53]; somnolence/drowsiness, 0.47 [0.09-2.58]; constipation, 0.64 [0.28-1.49]; pruritus 0.41 [0.05-3.51]). ADFs and non-ADFs had comparable efficacy and safety profiles, while both were more efficacious than placebo in reducing pain intensity.
Article
The roles of opioid receptors in pain and addiction have been extensively studied, but their function in mood disorders has received less attention. Accumulating evidence from animal research reveals that mu, delta and kappa opioid receptors (MORs, DORs and KORs, respectively) exert highly distinct controls over mood-related processes. DOR agonists and KOR antagonists have promising antidepressant potential, whereas the risk-benefit ratio of currently available MOR agonists as antidepressants remains difficult to evaluate, in addition to their inherent abuse liability. To date, both human and animal studies have mainly examined MORs in the etiology of depressive disorders, and future studies will address DOR and KOR function in established and emerging neurobiological aspects of depression, including neurogenesis, neurodevelopment, and social behaviors.
Article
Mitragyna speciosa Korth. leaves have been used for decades as a traditional medicine to treat diarrhea, diabetes and to improve blood circulation by natives of Malaysia, Thailand and other regions of Southeast Asia. Mitragynine is the major active alkaloid in the plant. To date, the role of mitragynine in psychological disorders such as depression is not scientifically evaluated. Hence, the present investigation evaluates the antidepressant effect of mitragynine in the mouse forced swim test (FST) and tail suspension test (TST), two models predictive of antidepressant activity and the effect of mitragynine towards neuroendocrine system of hypothalamic-pituitary-adrenal (HPA) axis by measuring the corticosterone concentration of mice exposed to FST and TST. An open-field test (OFT) was used to detect any association of immobility in the FST and TST with changes in motor activity of mice treated with mitragynine. In the present study, mitragynine at dose of 10 mg/kg and 30 mg/kg i.p. injected significantly reduced the immobility time of mice in both FST and TST without any significant effect on locomotor activity in OFT. Moreover, mitragynine significantly reduced the released of corticosterone in mice exposed to FST and TST at dose of 10 mg/kg and 30 mg/kg. Overall, the present study clearly demonstrated that mitragynine exerts an antidepressant effect in animal behavioral model of depression (FST and TST) and the effect appears to be mediated by an interaction with neuroendocrine HPA axis systems.
Article
Mitragynine is an indole alkaloid isolated from the Thai medicinal plant Mitragyna speciosa. We previously reported the morphine-like action of mitragynine and its related compounds in the in vitro assays. In the present study, we investigated the opioid effects of 7-hydroxymitragynine, which is isolated as its novel constituent, on contraction of isolated ileum, binding of the specific ligands to opioid receptors and nociceptive stimuli in mice. In guinea-pig ileum, 7-hydroxymitragynine inhibited electrically induced contraction through the opioid receptors. Receptor-binding assays revealed that 7-hydroxymitragynine has a higher affinity for micro-opioid receptors relative to the other opioid receptors. Administration of 7-hydroxymitragynine (2.5-10 mg/kg, s.c.) induced dose-dependent antinociceptive effects in tail-flick and hot-plate tests in mice. Its effect was more potent than that of morphine in both tests. When orally administered, 7-hydroxymitragynine (5-10 mg/kg) showed potent antinociceptive activities in tail-flick and hot-plate tests. In contrast, only weak antinociception was observed in the case of oral administration of morphine at a dose of 20 mg/kg. It was found that 7-hydroxymitragynine is a novel opioid agonist that is structurally different from the other opioid agonists, and has potent analgesic activity when orally administered.
Article
Kratom (Mitragynia speciosa korth) is recognized increasingly as a remedy for opioid withdrawal by individuals who self-treat chronic pain. A patient who had abruptly ceased injection hydromorphone abuse self-managed opioid withdrawal and chronic pain using kratom. After co-administering the herb with modafinil he experienced a tonic-clonic seizure, but he reported only modest abstinence once kratom administration stopped. We confirmed the identity of the plant matter he ingested as kratom and identified no contaminants or adulterants. We also conducted high-throughput molecular screening and the binding affinity at mu, delta and kappa receptors of mitragynine. We report the self-treatment of chronic pain and opioid withdrawal with kratom. The predominant alkaloid of kratom, mitragynine, binds mu- and kappa-opioid receptors, but has additional receptor affinities that might augment its effectiveness at mitigating opioid withdrawal. The natural history of kratom use, including its clinical pharmacology and toxicology, are poorly understood.
Assessment of Kratom Under the CSA Eight Factors and Scheduling Recommendations
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American Kratom Association. Personal Communication, Oliver Grundmann
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Ash, S., 2017. American Kratom Association. Personal Communication, Oliver Grundmann. University of Florida, Gainesville, FL.
DEA announces intent to schedule kratom. Drug Enforcement Administration. United States Department of Justice
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