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Abstract

Background: Kratom (Mitragyna speciosa) is a psychoactive plant native to Southeastern Asia that is receiving increased international attention as a potential therapeutic agent. While much of the limited scientific research on kratom is focused on its analgesic potential, kratom use also has important risks and benefits in the domain of mental health. Methods: We conducted a comprehensive systematic review of all studies on kratom use and mental health published between January 1960 and July 2017. Results: Findings indicate kratom's potential as a harm reduction tool, most notably as a substitute for opioids among people who are addicted. Kratom also enhances mood and relieves anxiety among many users. For many, kratom's negative mental health effects - primarily withdrawal symptoms - appear to be mild relative to those of opioids. For some users, however, withdrawal is highly uncomfortable and maintaining abstinence becomes difficult. Conclusion: Results inform clinicians working in the mental health and substance use fields, policy-makers, and researchers about the mental health effects of this plant.

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... Nonetheless, it is important to recognize that for centuries in Southeast Asia, kratom was used as a traditional medicine for its beneficial or therapeutic effects Singh et al., 2019a). Analogously, but not meeting the level of evidence documented for marijuana by the United States DHHS, therapeutic and beneficial use of kratom were extensively documented in self-report data from United States consumers as discussed in this review (e.g., Swogger and Walsh, 2018;Prozialeck et al., 2019;Smith et al., 2023a;Grundmann et al., 2023). US DHHS review of FDA's recommendation to place kratom in Schedule I of the CSA included consideration of the fact that many people use kratom to manage pain and opioid use and that banning kratom could lead to "intractable pain, psychological distress, suicide; transition to proven deadly opioids. ...
... Although self-report data cited above suggest that much kratom use relates to health and wellbeing, what is often referred to as "recreational use" also occurs Swogger and Walsh, 2018;Smith et al., 2021;Pont-Fernandez et al., 2023;Smith et al., 2024). This is not diagnostically defined and generally refers to people who occasionally use a substance for nonmedical reasons but who do not meet criteria for dependence or use disorder or withdrawal as used by FDA in recommendations for participants for human abuse potential studies (FDA, 2017a). ...
... This is not diagnostically defined and generally refers to people who occasionally use a substance for nonmedical reasons but who do not meet criteria for dependence or use disorder or withdrawal as used by FDA in recommendations for participants for human abuse potential studies (FDA, 2017a). In practice, distinguishing use to self-manage medical problems (e.g., mood disorders, pain, withdrawal), from use to improve productivity, exercise regimens, cognitive performance and focus, pleasurable mood states and sexual pleasure is not always clear in consumer self-reports of reasons for use (e.g., Swogger and Walsh, 2018;Veltri and Grundmann, 2019;Singh et al., 2020;Adzrago et al., 2022;Deebel et al., 2023). ...
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.
... Due to differences in climate and growing conditions, different kratom strains may contain varying amounts of alkaloids, which can produce diverse pharmacologic effects [3]. Kratom has been used for centuries in indigenous areas to treat anxiety; provide energy; and relieve pain, diarrhea, cough, and depression [6,7]. It is part of the culture and tradition in some geographical regions, such as the southern peninsula of Thailand [3,6]. ...
... Kratom has been used for centuries in indigenous areas to treat anxiety; provide energy; and relieve pain, diarrhea, cough, and depression [6,7]. It is part of the culture and tradition in some geographical regions, such as the southern peninsula of Thailand [3,6]. ...
... Pharmacy 2024,12,6 ...
Article
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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 (Mitragyna speciosa) is a plant-derived PS originating from the Southeast Asia with opiate properties in higher doses and psychostimulant in lower doses [61,62]. The prevalence of kratom abuse has been increasing in North America and Europe because it is a cheaper variant of opiates and is extensively appearing on online black markets as a sedative [61][62][63]. ...
... Approximately 4% of users experience hallucinations while consuming kratom [64]. A vulnerable group for the development of psychosis are those with premorbid psychotic disorders [63]. ...
... Kratom-induced psychosis is characterized by hallucinations, bizarre and paranoid delusions, aggressiveness, and agitation [61][62][63]. There are no specific guidelines for the treatment of kratom-induced psychosis, but case reports show the effectiveness of risperidone, olanzapine and anxiolytics [65]. ...
Article
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Purpose of Review Novel integrative reviews that give detail information regarding various psychoactive substances (PS) with ability of inducing psychosis in adults are lacking. This review aims to scope the latest knowledge about substance-induced psychosis (SIP) through the comprehensive review of the most common misused PS inducing psychosis. Recent Findings Epidemiological data on the prevalence of SIP are insufficiently harmonized, so clear conclusions for most PS can not be drawn. Etiological mechanisms include three pathophysiological mechanisms: the modulation of GABA transmission, NMDA antagonism, and effects on the monoaminergic system. Beside positive symptoms, PS may induce negative and cognitive symptoms. There are no uniform therapeutic guidelines for specific SIP, but some antipsychotics appear to be more effective than others. It is likely that the conversion rate of SIP to schizophrenia may be higher in the future because novel PS with a higher psychotic potential are increasingly being consumed. Summary This review presents epidemiological data, etiological mechanisms, details of clinical pictures, and treatment options for psychoses induced by specific PS.
... Kratom's effects on humans are dose-dependent: lowdose intake of kratom has a stimulating effect similar to caffeine, while higher doses can induce opioid-like effects (9). Long-term use of kratom can cause side effects, including anorexia, weight loss, insomnia, and kratom dependence (9,10). ...
... Kratom's effects on humans are dose-dependent: lowdose intake of kratom has a stimulating effect similar to caffeine, while higher doses can induce opioid-like effects (9). Long-term use of kratom can cause side effects, including anorexia, weight loss, insomnia, and kratom dependence (9,10). Although kratom's toxicity is far lower than that of conventional drugs, there are still reports pointing out the negative effects and lethal risk (11). ...
... As comparison, a systematic review by Swogger and Walsh (2018) also reported similar findings, wherein kratom exhibited therapeutic potential for opioid replacement therapy and may induce antidepressant and anxiolytic effects, but the main concern is kratom withdrawal symptoms which make it difficult to maintain abstinence in some regular users [9]. In another systematic review aimed to investigate pre-clinical evidence of the efficacy of kratom as a therapeutic agent and its safety concern also revealed similar findings, whereby kratom has therapeutic value in treatment of opioid and alcohol withdrawal and dependence, but its potential to induce kratom withdrawal and dependence on regular use is one of the major concern for safety. ...
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.
... Anti-anxiety/anti-psychotic via actions at the trace amino acid receptor Carbonaro, Gatch [11] Kratom Substitute for opioids among people who are addicted. Kratom also enhances mood and relieves anxiety Swogger, Walsh [71] As commonly used analgesics, such as opioids, have a high risk of being addictive, psychoceuticals that are en route to being approved may eventually replace opioids in clinical practice. For instance, Kratom exhibits analgesic effects by acting as an MOR agonist [28,71]. ...
... Kratom also enhances mood and relieves anxiety Swogger, Walsh [71] As commonly used analgesics, such as opioids, have a high risk of being addictive, psychoceuticals that are en route to being approved may eventually replace opioids in clinical practice. For instance, Kratom exhibits analgesic effects by acting as an MOR agonist [28,71]. In addition, psychedelics have also been demonstrated to help reduce cravings for patients undergoing withdrawal from opioid use. ...
...  N, N-dimethyltryptamine's side effects include increased levels of corticotropin, cortisol, prolactin, and growth hormone when administered to human volunteers [11].  Kratom has shown mental health effects, primarily withdrawal symptoms [71]. ...
Article
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Psychoceuticals have brought benefits to the pharmacotherapeutic management of central nervous system (CNS) illnesses since the 19th century. However, these drugs have potential side effects or lack high response rates. This review covers twenty drugs’ biochemical mechanisms, benefits, risks, and clinical trial reports. For this study, medications from seven psychoceutical organizations were reviewed and evaluated. Nineteen drugs were chosen from the organizations, and one was selected from the literature. The databases used for the search were Pubmed, Google Scholar, and NIH clinical trials. In addition, information from the organizations’ websites and other sources, such as news reports, were also used. From the list of drugs, the most common targets were serotonergic, opioid, and N-methyl-D-aspartate (NMDA) receptors. These drugs have shown promise in psychiatric illnesses such as substance abuse, post-traumatic stress disorder (PTSD), anxiety, depression, and neurological conditions, such as Parkinson’s disease, traumatic brain injury, and neuroinflammation. Some of these drugs, however, are still early in development, so their therapeutic significance cannot be determined. These twenty drugs have promising benefits, but their clinical usage and efficacy must still be explored.
... Kratom, also known as Mitragyna speciosa Korth., is a Southeast Asian plant with a wide variety of traditional uses. Its complex pharmacology produces various reported effects, including analgesia, stimulation and mood enhancement, and mitigation of withdrawal from classical opioids and other unwanted substances, such as alcohol (Babu et al., 2008;Smith, Dunn, et al., 2021;Swogger & Walsh, 2018). Kratom's popularity outside of Southeast Asia has grown considerably over the past decade. ...
... Studies, across Western and Eastern cultures, demonstrate that people use kratom as an alternative to, or harm reduction strategy for, opioids (Swogger & Walsh, 2018). It is also used because it is easy to obtain through internet sources and in local shops, following a specific trend that has been common for novel psychoactive substances in the last two decades (Schifano et al., 2005). ...
... Presently kratom is banned in Indiana, Arkansas, Alabama, Rhode Island, Vermont, and Wisconsin. Although the US Drug Enforcement Administration (DEA) proposed Kratom classification to Schedule I in August 2016 this decision was reversed after 45 days because of petitions by Kratom users (Swogger & Walsh, 2018). To date, Kratom is not regulated by the US Food and Drug Administration (FDA) and can be legally purchased in different forms, including capsules, powders, or flavored tea and concentrated extracts. ...
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Kratom (Mitragyna speciosa Korth.) use has increased substantially over the past decade outside of its indigenous regions, especially for the self-treatment of psychiatric conditions. An anonymous, cross-sectional, online survey was completed by 4,945 people who use kratom (PWUK) between July 2019 and July 2020. A total of 2,296 respondents completed an extended survey utilizing clinical scales for attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), depressive and anxiety disorders. PWUK and met criteria for ADHD, PTSD, depressive or anxiety disorders were primarily middle-aged (31-50 years), employed, more likely to have college-level education (81.3% vs. 80.0%), and reported increased concurrent or prior use of kratom with cannabis products, cannabidiol, and benzodiazepines. In all psychiatric conditions, PWUK reported less depressive and anxious moods. Self-reported quality of life was worse in psychiatric conditions whereas current pain was more severe. Based on this observational study, further clinical studies are warranted for kratom.
... Mitragynine (Fig. 2), a major alkaloid kratom, binds to the µ-opioid and δ-opioid receptors, while 7-hydroxy mitragynine has a stronger affinity to µ-opioid receptor than other receptors (Matsumoto, 2006). Mitragynine showed 16 times more affinity for µopioid and δ-opioid receptors and 200 times less affinity than morphine (Yue et al., 2018), resulting in analgesic opioid activity for both mitragynine and 7-hydroxy mitragynine (Swogger & Walsh, 2018). Mitragynine has stimulant effects at low doses and sedative effects at high doses (Swogger & Walsh, 2018), and it is not found in other plants (Kikura-Hanajiri et al., 2009). ...
... Mitragynine showed 16 times more affinity for µopioid and δ-opioid receptors and 200 times less affinity than morphine (Yue et al., 2018), resulting in analgesic opioid activity for both mitragynine and 7-hydroxy mitragynine (Swogger & Walsh, 2018). Mitragynine has stimulant effects at low doses and sedative effects at high doses (Swogger & Walsh, 2018), and it is not found in other plants (Kikura-Hanajiri et al., 2009). This compound is exclusively found in M. speciosa but not in any other genus of Mitragyna (Lesiak et al., 2014;Sanagi et al., 2013). ...
Article
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Kratom (Mitragyna speciosa Korth) has been identified as a New Psychoactive Substance (NPS) by the United Nations Office on Drugs and Crime (UNODC) and included in the list of prohibited ingredients in food supplements and traditional medicine by Indonesian FDA. Therefore, a rapid, easy, and reliable analytical method is necessary to detect and quantify this plant and its products. This study developed a method for the detection and quantification of kratom products based on a unique compound, mitragynine, as a biomarker. A previous survey of determining mitragynine in Kratom using GC-MS, LC-MS/MS, UPLC, and HPLC-PDA. Previously, the HPLC-PDA method used a C8 column. Yet, for efficiency, it is also necessary to develop a test method using a C18 column. Analysis was performed using an HPLC - PDA system with Waters Atlantis T3-C18 (250 x 4.6 mm, 5 µm) column. The mobile phase comprises acetonitrile and formic acid 0.05%, pH 5.0 (75:25 v/v), delivered at a 1.0 mL/min flow rate. Detection was carried out at a wavelength of 225 nm. The analytical method was validated with test parameters of selectivity, system suitability, accuracy, precision, linearity, detection limit, and quantification limit. The validation study demonstrated an excellent linear concentration range of 1.96 - 6.01 µg/mL with a correlation coefficient of 0.9996; the detection limit is 0.14 µg/mL, while the limit of quantification is 0.45 µg/mL—accuracy method of 98.88 - 101.44% and a bias of 0.27%. The percent relative standard deviation for six independent assay determinations was 0.67%, and the intermediate precision was 1.56% on two days. The mitragynine amounts in these materials ranged from 6.01 to 6.31 mg/g of dried leaf material. Based on the research results, it can be concluded that the method developed provides quick, simple, reliable, accurate, and valid, and has an advantage over existing methods in terms of simplicity of sample preparation, short analysis time, and cost-effectiveness compared to GCMS and LCMS/MS and can be applied for future analysis in Kratom samples.
... 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. ...
... 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.
... 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). ...
... Absent regulatory oversight, it is critical that kratom is not advertised as merely another "herbal supplement" without no potential for physical dependence. Ideally, decision-making by individual consumers would be done with medical consultation, particularly when use is for self-treatment of chronic conditions (Swogger and Walsh, 2018). Ultimately, our findings suggest that kratom products, during this 2020-2022 period, were deemed to be helpful for some and a hindrance to others, but that, irrespective of use motivations or outcome, consumers were frustrated and placed at risk by a regulatory wilderness that they were, and are, largely navigating on their own. ...
Article
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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.
... The plant is easily accessible in the US at gas stations, tobacco shops, and over the Internet. People usually ingest it by chewing its leaves, or boiling it in water and taking it as a tea, or as pills, or by smoking or vaporizing the leaves [5]. Consumers are known to use kratom for pain relief, diarrhea, euphoria, depression, and management of opioid withdrawal [6]. ...
... Psychiatric complications have been linked to kratom use in previous case reports, and the Centers for Disease Control and Drug Enforcement Administration have stated that kratom may cause psychosis or psychosis-like symptoms [5,7]. Despite this, multiple studies have found no relation between kratom use and psychosis. ...
Article
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Kratom is a plant extract readily available for purchase in the USA. It is known to produce both stimulant and opioid-related effects, predisposing it to abuse. The long-term effects of kratom are poorly understood. In rare cases, serious side effects have been reported. Here, we report a case of a patient with a history of bipolar type schizoaffective disorder presenting with acute onset paranoia and delusions. The patient had been hospitalized seven times previously with psychotic symptoms, with no reported history of paranoid delusional thought content in previous admissions. It was discovered that the patient had been ingesting increasingly large quantities of kratom in the weeks leading up to the admission. It is believed that kratom may be responsible for the novel symptoms contributing to the patient’s acute psychiatric decompensation.
... 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). ...
... Kratom products are increasingly used for self-management of mental health symptoms and other ailments. Several alkaloids present in kratom impact neurobiological systems involved in psychiatric conditions; hence, it is imperative for clinicians to understand the patterns of use among their clinical populations (Swogger & Walsh, 2018). There are few studies which have investigated the prevalence of kratom use among those with serious mental illness who use substances. ...
... 1 As currently understood in recent reports, kratom interacts with opioid receptors in a dose-dependent manner; low doses (1-5 g of raw leaves) provide a stimulating effect used to enhance mood and relieve anxiety, higher doses (5-15 g of raw leaves) can induce pain relief and euphoria, and higher doses sedation. [2][3][4][5] However, in recent years, kratom use has been increasing in the USA, Canada, and other European countries as a natural remedy for pain relief as an opioid substitute for mood and anxiety disorders. [6][7][8] The use of kratom has become a concern, prompting the Drug Enforcement Administration (DEA) to classify it as a drug of concern. ...
... Some published studies have found no direct link between kratom use and the development of psychosis. 4 However, our case report indicates a potential association. In contrast, others had observed the occurrence of psychosis in kratom users when other drugs were involved, such as methamphetamine. ...
... Kratom, also known as Mitragyna speciosa Korth., is a Southeast Asian plant with a wide variety of traditional uses. Its complex pharmacology produces various reported effects, including analgesia, stimulation, mood enhancement, and mitigation of withdrawal from opioids and other problematic substances, such as alcohol (Babu et al., 2008;Smith, Dunn, et al., 2021;Swogger & Walsh, 2018). Kratom's popularity outside of Southeast Asia has grown over the past decade. ...
... Globally, studies demonstrate that people use kratom as a harmreduction strategy, substituting kratom for opioids. (Garcia-Romeu et al., 2020;Grundmann, 2017;Singh et al., 2022;Smith & Lawson, 2017;Swogger & Walsh, 2018). This substitution for purposes of harm-reduction has arisen, in part, because kratom is easy to obtain online and in local shops, following purchasing trends that have been common for novel psychoactive substances in recent decades (Schifano et al., 2005). ...
Article
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Kratom (Mitragyna speciosa Korth.) use has increased substantially over the past decade outside of its indigenous regions, especially for the self-treatment of psychiatric conditions. An anonymous, cross-sectional, online survey was completed by 4,945 people who use kratom (PWUK) between July 2019 and July 2020. A total of 2,296 respondents completed an extended survey that included clinical scales for measuring attention deficit hyperactivity disorder (ADHD), posttraumatic stress disorder (PTSD), depressive and anxiety disorders. PWUK and met criteria for ADHD, PTSD, depressive or anxiety disorders were primarily middle-aged (31–50 years), employed, college-level educated, and reported greater concurrent or prior use of kratom with cannabis, cannabidiol, and benzodiazepines. For all psychiatric conditions, PWUK reported decreased depressive and anxious moods than before kratom use. Based on this self-report study, observational and other clinical studies are warranted for kratom.
... Self-report data posted on internet websites were summarized in several kratom use reviews (e.g., Cinosi et al 2015;Henningfield et al. 2018Henningfield et al. , 2022Swogger and Walsh 2018;Veltri and Grundmann 2019). These data suggest that kratom intake is typically limited by non-life-threatening but discomfort-producing gastrointestinal symptoms and/ or undesirable lethargy. ...
... These data suggest that kratom intake is typically limited by non-life-threatening but discomfort-producing gastrointestinal symptoms and/ or undesirable lethargy. Furthermore, for most kratom consumers, higher doses do not produce the powerful euphorialike highs sought by people who recreationally use opioids, cocaine, and amphetamine and that is an incentive for the frequent dose escalation that contributes to the high risk of overdose deaths associated with such drugs (Swogger et al. 2022;Swogger and Walsh 2018;Henningfield et al. 2018Henningfield et al. , 2022. ...
Article
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Rationale Kratom derives from Mitragyna speciosa (Korth.), a tropical tree in the genus Mitragyna (Rubiaceae) that also includes the coffee tree. Kratom leaf powders, tea-like decoctions, and commercial extracts are taken orally, primarily for health and well-being by millions of people globally. Others take kratom to eliminate opioid use for analgesia and manage opioid withdrawal and use disorder. There is debate over the possible respiratory depressant overdose risk of the primary active alkaloid, mitragynine, a partial μ-opioid receptor agonist, that does not signal through ß-arrestin, the primary opioid respiratory depressant pathway. Objectives Compare the respiratory effects of oral mitragynine to oral oxycodone in rats with the study design previously published by US Food and Drug Administration (FDA) scientists for evaluating the respiratory effects of opioids (Xu et al., Toxicol Rep 7:188–197, 2020). Methods Blood gases, observable signs, and mitragynine pharmacokinetics were assessed for 12 h after 20, 40, 80, 240, and 400 mg/kg oral mitragynine isolate and 6.75, 60, and 150 mg/kg oral oxycodone hydrochloride. Findings Oxycodone administration produced significant dose-related respiratory depressant effects and pronounced sedation with one death each at 60 and 150 mg/kg. Mitragynine did not yield significant dose-related respiratory depressant or life-threatening effects. Sedative-like effects, milder than produced by oxycodone, were evident at the highest mitragynine dose. Maximum oxycodone and mitragynine plasma concentrations were dose related. Conclusions Consistent with mitragynine’s pharmacology that includes partial µ-opioid receptor agonism with little recruitment of the respiratory depressant activating β-arrestin pathway, mitragynine produced no evidence of respiratory depression at doses many times higher than known to be taken by humans.
... 11, 13 Kratom can be commonly bought in the U.S. through online retailers and smoke shops, 8 businesses that tend to geographically cluster around college campuses. 14 Kratom users cite motivations for use including improving mood, increasing alertness, and managing pain, 7,[15][16][17] suggesting that mental health concerns may motivate use. Some kratom users also indicate use of kratom to support fitness goals. ...
... 3,4,[20][21][22][23] Withdrawal from kratom is more mild than opioid withdrawal. 17 This rise of kratom use in the United States is potentially dangerous, particularly to groups that may have increased risk for use. Some work has investigated demographic correlates of kratom use, finding that kratom use in the U.S. is more prevalent among men, White individuals, adults between the ages of 18-50, and marijuana users. ...
Article
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Objective: Kratom use represents a growing risk for public health. The present study examined demographic and behavioral factors linked with kratom use. Participants: Participants were college students in the United States who participated in the 2019-2020 Healthy Minds Study. Methods: Participants completed survey-based assessment of kratom use and related demographic, behavioral, and mental health variables. Results: Kratom use was linked with being White, male or transgender/gender nonconforming, identifying as a sexual minority, use of alcohol or marijuana, and depressive symptoms. Kratom use was not uniquely linked to exercise or anxiety. Conclusions: The results of the present study can be used to inform initial targeting of efforts to reduce kratom use among college students.
... Such information needs to be gathered from a variety of sources, as kratom products in the US are largely unregulated and unstandardized. In surveys, use is often attributed to "self-treatment" of chronic pain, fatigue, mental health (e.g., anxiety, depression), and/or substance use disorder (SUD) symptoms, or goals of improving energy and mood (3,(7)(8)(9)(10). These motivations are consonant with findings from smaller surveys conducted in Malaysia or Thailand (Singh et al. 2016; Singh et al. 2019 (11)(12)(13)(14). ...
... Healthcare providers should be made aware of kratom and assess patients for use, particularly among those with comorbidities or for whom medications are being prescribed (34). Sensitivity to factors motivating kratom use should be considered a best practice when treating this population and steadfastly promoted in the clinical exchange so as to decrease stigma and maximize the likelihood for open dialogue (10). That many people using kratom are doing so, in part, to "self-treat" conditions that may be clinically addressable, makes quality medical engagement ever more urgent. ...
Article
Background: Mitragyna speciosa (kratom) is increasingly used in the United States for its pharmacological effects. Kratom's relative novelty makes for a dynamic situation, such that use motivations are not firmly established and may be changing. Investigators and clinicians require frequent updates on kratom trends. Objectives: To assess the current state of kratom-use initiation, sourcing, motivations, preference, conceptualizations, and perceived stigma, using survey responses from current and former users. Methods: Between April-May 2021 we recontacted 289 respondents who reported lifetime kratom use (on an unrelated survey) to answer kratom-specific questions. Results: The sample (N=129) was majority female (51.9%) and white (71.9%). Most (69.0%) reported first trying kratom after 2015. Mean age of use initiation (29.9 years) was older than for other substances, including opioids. Kratom ranked as a preferred substance by 48.5%. The strongest drug association with past-year kratom use was vaped nicotine (OR=3.31,95% CI 1.23-8.88). Use was less likely among those prescribed buprenorphine in the past year (OR=0.03, CI 0.01-0.28). Past-month cannabis use (OR=4.18,CI 1.80-9.72) had the strongest association with past-month kratom use. Over 40 use motivations were endorsed, many (but not all) supporting the "self-treatment" narrative of kratom use, including use as an opioid, alcohol, or stimulant substitute. Treatment shortfalls were associated with decisions to try kratom. Conclusions: Kratom use motivations are diversifying, with multiple factors driving use. As sales continue to increase, the public-health, clinical, and policy responses to kratom should be grounded in rigorous bench-to-bedside scientific research. Comprehensive study of kratom is currently lacking.
... Kratom (Mitragyna speciosa, Korth) is a plant originating from Southeast Asia [17]. Locally, kratom is traditionally consumed for its analgesic and opiate-like properties [18] .In Western countries, kratom has gained popularity and is typically consumed to self-treat opioid withdrawal symptoms including anxiety [19][20]. ...
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Introduction: Neuroinflammation marked by increased toll-like receptor (TLR)-4 expression contributes to the pathogenesis of anxiety disorders. Mitragynine, an indole alkaloid derived from the kratom plant (Mitragyna speciosa Korth), shows promise as a potential pharmacotherapeutic agent for anxiety due to its anti-inflammatory activity. However, the mechanism involved in its anxiolytic effect remains unclear. Aims: This study investigated the effects of mitragynine on anxiety-like behaviours, TLR4 expression and oxidative stress in the frontal cortex of rats treated with lipopolysaccharide (LPS). Methodology: Rats received a single 1 mg/kg LPS injection intraperitoneally (i.p.) to induce anxiety. Mitragynine was then administered at the doses of 1, 5 or 10 mg/kg body weight 1h post-LPS administration. Impact of mitragynine on anxiety was assessed using both open field test (OFT) and elevated plus maze (EPM). TLR4 expression was measured using western blot, while oxidative stress markers (MDA, GSH, GPx, CAT) were measured using protein assays. Results: Mitragynine ameliorated LPS-induced anxiety behaviours in the EPM. Mitragynine (5 and 10 mg/kg) reversed the effect of LPS on TLR4 expression in the rats’ brains. All doses of mitragynine reduced lipid peroxidation in the frontal cortex of LPS-treated rats. Conclusion: Mitragyninemitigates LPS-induced anxiety by alleviating lipid peroxidation in the frontal cortex.
... Havil.) is a tropical herbaceous plant in the Rubiaceae family, native to and widely distributed throughout southeast Asia, particularly in Malaysia, Indonesia, and Thailand. 1 It is traditionally used to treat a wide range of symptoms such as diarrhea, fever, and coughs. Additionally, it is used as a stimulant to boost physical tolerance and enhance work performance, 2 as well as an analgesic due to its pain-relieving properties. ...
Article
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BACKGROUND Kratom (Mitragyna speciosa) has a long history of traditional use. It contains various alkaloids and polyphenols. The properties of kratom's alkaloids have been well‐documented. However, the property of kratom's polyphenols in water‐soluble phase have been less frequently reported. This study assessed the effects of water‐soluble Mitragyna speciosa (kratom) extract (MSE) on gut microbiota and their metabolite production in fecal batch culture. RESULTS The water‐soluble kratom extract (MSE0) and the water‐soluble kratom extract after partial sugar removal (MSE50) both contained polyphenols, with total phenolic levels of 2037.91 ± 51.13 and 3997.95 ± 27.90 mg GAE/g extract, respectively and total flavonoids of 81.10 ± 1.00 and 84.60 ± 1.43 mg CEQ/g extract. The gut microbiota in fecal batch culture was identified by 16S rRNA gene sequencing at 0 and 24 h of fermentation. After fermentation, MSE50 stimulated the growth of Bifidobacterium more than MSE0. MSE0 gave the highest total fatty acids level among the treatments. The phenolic metabolites produced by some intestinal microbiota during fecal fermentation at 24 h were analyzed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The major metabolite of biotransformation of both water‐soluble MSEs by intestinal microbiota was pyrocatechol (9.85–11.53%). CONCLUSION The water‐soluble MSEs and their produced metabolites could potentially be used as ingredients for functional and medicinal food production that supports specific gut microbiota. © 2024 Society of Chemical Industry.
... These data suggest most U.S. kratom users are polysubstance users. They may be using to offset negative effects of multiple substances or to manage common symptoms that drive individuals to use substances (e.g., comorbid mood disorders) (62). Given that data demonstrate kratom is mostly consumed by polysubstance users, and that it may have utility for multiple SUDs, further investigation into its utility as a harm reduction tool for polysubstance use disorders is warranted. ...
Article
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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.
... Kratom also interacts with NE and 5HT, 26,27 and could be mediating the euphoriant, antidepressant, and antipsychotic effects. 28 Seizures are among Kratom's symptoms. 29 Our results are consistent with the proconvulsant effects of "fresh" Kratom extracts. ...
Article
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Kratom (Mitragyna speciosa) is used as a stimulant, an opioid-like analgesic, and a sedative. However, Kratom consumption has profound effects, such as seizures, withdrawal, hallucinations, coma, and cardiac or respiratory arrest. We tested Kratom's effects on pentylenetetrazole-induced seizures in adult zebrafish (D rerio) using hydroethanolic Kratom extracts. Kratom extracts have pro-convulsant effects at low concentrations (10-4-10-1 mg/mL), while sedation occurs at higher concentrations. In the open-field test, Kratom has no anxiolytic effects; however, "social" behavior was lost at high concentrations (1.0 mg/mL). Our results confirm the possible proconvulsant role of Kratom while questioning its anxiolytic effects.
... Kratom (Mitragyna speciosa) is a plant native to Southeast Asia that has been used for centuries as a traditional medicine and herbal remedy. Kratom is consumed orally by chewing fresh or dried leaves, drinking crushed or boiled leaves in a tea, or by consuming encapsulated leaf powder [1][2][3][4]. In the United States, there are an estimated 10-16 million kratom users [3,[5][6][7][8][9]. ...
Article
Aims: Mitragynine (MG) is an alkaloid found in Mitragyna speciosa (kratom), a plant used to self-treat symptoms of opioid withdrawal and pain. Kratom products are commonly used in combination with cannabis, with the self-treatment of pain being a primary motivator of use. Both cannabinoids and kratom alkaloids have been characterized to alleviate symptoms in preclinical models of neuropathic pain such as chemotherapy-induced peripheral neuropathy (CIPN). However, the potential involvement of cannabinoid mechanisms in MG's efficacy in a rodent model of CIPN have yet to be explored. Main methods: Prevention of oxaliplatin-induced mechanical hypersensitivity and formalin-induced nociception were assessed following intraperitoneal administration of MG and CB1, CB2, or TRPV1 antagonists in wildtype and cannabinoid receptor knockout mice. The effects of oxaliplatin and MG exposure on the spinal cord endocannabinoid lipidome was assessed by HPLC-MS/MS. Key findings: The efficacy of MG on oxaliplatin-induced mechanical hypersensitivity was partially attenuated upon genetic deletion of cannabinoid receptors, and completely blocked upon pharmacological inhibition of CB1, CB2, and TRPV1 channels. This cannabinoid involvement was found to be selective to a model of neuropathic pain, with minimal effects on MG-induced antinociception in a model of formalin-induced pain. Oxaliplatin was found to selectively disrupt the endocannabinoid lipidome in the spinal cord, which was prevented by repeated MG exposure. Significance: Our findings suggest that cannabinoid mechanisms contribute to the therapeutic efficacy of the kratom alkaloid MG in a model of CIPN, which may result in increased therapeutic efficacy when co-administered with cannabinoids.
... As kratom products proliferate and are increasingly advertised to consumers as natural products or supplements for enhancing mood, performance, cognition, and energy, it may be that more middle-class, educated US adults with heterogenous substance use histories try these nonregulated kratom products for curiosity or recreation, but not necessarily for self-treatment of comorbid conditions. C15P31 6,9,35,92,111,113 As data are largely anecdotal and nationally representative surveys only now beginning to include items assessing kratom use, it remains unknown not only how many people are using kratom globally but also how many may have moderated their opioid use or achieved short-or long-term remission from OUD as a result of nonmedical kratom use. Although survey, qualitative, and anecdotal evidence implicate kratom as a perceived viable opioid substitute or method for managing opioid dependence and SUD symptoms, it is incumbent upon researchers and clinicians to rigorously evaluate and study these seeming trends further. ...
Chapter
Kratom (Mitragyna speciosa) is a tree in the coffee family, indigenous to Southeast Asia (SEA), whose leaves have historically been used as a natural remedy and for its purported stimulating and analgesic properties. Kratom has gained popularity in recent years in the United States, where internet-based sales have driven growing numbers of people to experiment with kratom products. Kratom contains over 40 unique alkaloids displaying complex pharmacological properties including opioid- and non opioid-receptor mediated effects. Data from animal research indicates therapeutic potential of kratom; for instance, as an analgesic agent or in mitigating opioid and alcohol withdrawal symptoms. Some adverse effects and risks are also attributable to kratom and its alkaloids, including possible liver damage and potential for dependence, particularly in the context of high dosage and/or chronic administration. However, in comparison to commonly used opioid medications, these risks are generally lower for kratom, consistent with human observational data from SEA and the US. Prevalence of kratom use remains difficult to conclusively assess, with estimates ranging between 1.8 to 15.6 million kratom-using adults in the US alone. The limited human data, comprised of survey and case report, suggest kratom may be effective for pain relief, to address mood and anxiety symptoms, and as a potential future aid in the treatment of substance use disorders and drug withdrawal. Overall, limited data indicate kratom and its alkaloids warrant a significant investment of rigorous basic and clinical research to better characterize its pharmacology, potential risks, and therapeutic benefits.
... Of course, the motivations to use kratom for increasing energy or enhancing productivity are not mutually exclusive with other motivations, including use as a drug substitute, nor are they mutually exclusive with respect to use or polydrug use to achieve recreational pleasure or enjoyment. Use for the purpose of achieving pleasant psychoactive and somatic states that include euphoria or a "high" are wellrepresented in the literature [5•, 55, 65, 70•] and should not be overshadowed by the initial emergence of kratom in the USA primarily as self-reported form of opioid substitution or SUD symptom management [73,78]. Regardless of whether pleasant, pleasurable, or mood enhancing states (i.e., positive reinforcement) and not merely relief from unpleasant states through analgesia, antidepressant, or antinociceptive effects (i.e., negative reinforcement) were sought out explicitly or manifested as part of a larger effect profile is unknown. ...
Article
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Purpose of Review Use of “kratom” products, derived from the bioactive botanical Mitragyna speciosa have increased amidst US polydrug use epidemics. Kratom alkaloids interact with opioid, serotonergic, adrenergic, and other receptors and regular users have described experiencing a wide range of effects. Some with polydrug use histories have reported using kratom as a substitute for other drugs or to nonmedically self-manage substance use disorder (SUD) symptoms. Data describing this remain scare and come from self-report. We review this literature describing kratom use as a drug substitute, or as a nonmedical “self-treatment” for attenuating dependence or SUD symptoms. Recent Findings Kratom products have been documented as being used as a licit and illicit opioid substitute. Use to reduce alcohol or stimulant consumption is less well documented. Although prior and current polydrug use appear common among a some kratom users, it is unclear if co-use is contemporaneous or concomitant. Temporal order of use initiation is typically undocumented. Use for energy and recreation are also increasingly reported. Summary Data on kratom consumption come primarily from self-report with significant limitations. Until controlled human laboratory studies have been conducted, we can presently only describe what is known about human kratom use based on self-report. Such data describe real-world kratom use, leaving unaddressed human abuse liability or therapeutic potential of kratom alkaloids. Clinicians should be mindful of use motivations among people with SUD histories, sensitively assessing use. The paucity of data highlights the urgent need to increase funding and research for understanding kratom’s effects in humans.
... Various epidemiological studies estimate the lifetime kratom use among the adult American population to range between 0.9 and 6.1% [3,4]. Motivations for use include "self-management" of symptoms related to chronic pain, fatigue, substance use disorders, and psychiatric conditions along with attenuating opioid-withdrawal [1,[5][6][7]. Use of kratom as a short-or long-term substitute for opioids, stimulants, and alcohol has also been described [2,8]. Despite the numerous perceived therapeutic benefits reported by those who use kratom, there are no clinical safety/tolerability studies, human abuse potential studies, or randomized clinical trials investigating kratom's risks or efficacy for any clinical indication [9,10]. ...
Article
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Background “Kratom” commonly refers to the botanical Mitragyna speciosa, native to Southeast Asia, which is increasingly used globally for its unique pharmacological effects. Motives for using the whole plant material or kratom-derived products include self-management of pain, mental health disorders, symptoms related to substance use disorders, and/or to increase energy. In the United States, kratom products have varying alkaloid content, potencies, and marketing profiles. There is little regulatory oversight over kratom, as it is currently not approved as a dietary supplement by the Food and Drug Administration. This results in substantial variability in labeling of kratom products and the product information provided to consumers. Methods In January 2023, we evaluated the American Kratom Association’s Good Manufacturing Practices (GMP) qualified vendors’ websites (n = 42) using the well-established and validated DISCERN instrument to examine the quality of health information provided to consumers. DISCERN contains 15 five-point Likert-scale questions on specific criteria, with the highest possible score being 75, indicating that all the DISCERN criteria have been fulfilled by the website (i.e., the highest quality information is provided to consumers). Results The mean DISCERN score for all evaluated online kratom vendors was 32.72 (SD = 6.69; score range 18.00–43.76). Overall, vendors scored higher on DISCERN questions assessing the website’s reliability, as vendors typically provided clear information for consumers about product availability, purchasing, shipping, etc. On average, vendors scored poorly on the DISCERN section pertaining to the quality of the health information provided. Information on kratom’s potential risks and benefits was particularly insufficient. Conclusions Consumers require high quality information in order to make informed decisions concerning use, which entails disclosure of known risks and potential benefits. The online kratom vendors evaluated in this study should consider enhancing the quality of health information provided, especially information regarding kratom’s risks and benefits. Further, consumers should be made aware of current knowledge gaps related to kratom’s effects. Clinicians must also be aware of the lack of evidence-based information available to their patients who use kratom or are interested in using kratom products, in order to facilitate educational discussions with them.
... The fact that the online surveys to date are convenience samples of self-selected respondents limits their generalizability to the larger population of kratom consumers. However, the findings are consistent with observations in residential drug treatment programs (e.g., Smith and Lawson 2017 ) and field survey studies in SEA ( Leong Bin Abdullah et al., 2021 ;Singh et al., 2014Singh et al., , 2020Singh et al., , 2018, and in recent global reviews of kratom use and effects Karunakaran et al., 2022 ;Swogger and Walsh, 2018 ;WHO ECDD, 2021 ). Although kratom intake to self-manage OUD and opioid withdrawal is of particular interest in light of the opioid epidemic in the US, the aforementioned surveys in the US and Southeast Asia (SEA) suggest that the reason most consume kratom is for its diverse effects including as an alternative to caffeinated beverages for stimulating and alerting effects, and to improve overall health, functioning, and well-being. ...
... While kratom has been used in Southeast Asia for hundreds of years, it is only within the past 20 years that kratom use has expanded to Europe and the Americas [1,4,5,13,14]. In the United States, kratom products are usually used for the self-management of pain, opioid use disorder, and depression [13][14][15][16][17][18][19]. The most widely used kratom products include finely ground dried leaf powder (either alone or formulated into capsules or tablets) or concentrated leaf extracts [3,4,16]. ...
Article
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Kratom (Mitragyna speciosa) is a tropical tree that is indigenous to Southeast Asia. Kratom leaf products have been used in traditional folk medicine for their unique combination of stimulant and opioid-like effects. Kratom is being increasingly used in the West for its reputed benefits in the treatment of pain, depression, and opioid use disorder (OUD). Recent studies from the United States Food and Drug Administration (FDA, Silver Spring, MD, USA) and our laboratory have shown that many kratom products being sold in the United States are contaminated with potentially hazardous levels of lead (Pb). In this commentary, we discuss the public health implications of the presence of Pb in kratom products, particularly as they relate to the predicted levels of Pb exposure among kratom users. We also considered the specific toxic effects of Pb and how they might relate to the known physiologic and toxicologic effects of kratom. Finally, we consider the possible sources of Pb in kratom products and suggest several areas for research on this issue.
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
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
Mitragyna speciosa Korth (kratom) is a tropical indigenous tree of Southeast Asia. It is commonly consumed by the people due to its various pharmacological properties. The leaves of this plant are traditionally used for the treatment of several diseases including pain, fever, cough, anxiety, depression, obesity, diarrhoea, wound healing, diabetes, hypertension as well as for the prevention of cancer and improvement of sexual performance. Phytochemical investigations have confirmed the presence of more than forty alkaloids along with the presence of other bioactive secondary metabolites. Among the alkaloids isolated, mitragynine and 7-hydroxymitragynine along with their derivatives have been widely evaluated and reported to possess various pharmacological effects. Hence, the aim of this review is to shed light on the traditional uses of kratom and the scientific studies to justify the folkloric claims and active principles responsible for the various medicinal effects associated with the leaves of this plant. This review highlights the potential benefits and toxicities associated with M. speciosa leaves along with the phytochemistry. Moreover, the existing gaps in the field of M. speciosa study have been identified along with the future directions to further avail the benefits of this plant species.
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
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.
Article
Mitragynine (MG) is the primary active constituent of Mitragyna speciosa Korth (kratom), a psychoactive Southeast Asian plant with potential therapeutic use. Numerous studies support roles of dopaminergic system in drug reward. However, the involvement of the dopaminergic system in mediating MG reward and drug-seeking is poorly understood. Using conditioned place preference (CPP) paradigm, the present study aims to evaluate the roles of the dopamine (DA) D1 receptor in the acquisition and expression of MG-induced CPP in rats. The effects of SCH-23390, a selective DA D1 receptor antagonist, on the acquisition of MG-induced CPP were first investigated. Rats were pre-treated systemically with SCH-23390 (0, 0.1 and 0.3mg/kg, i.p.) prior to MG (10mg/kg) conditioning sessions. Next, we tested the effects of the DA D1 receptor antagonist on the expression of MG-induced CPP. Furthermore, the effects of a MG-priming dose (5mg/kg) on the reinstatement of extinguished CPP were tested. The results showed that SCH-23390 dose-dependently suppressed the acquisition of a MG-induced CPP. In contrast, SCH-23390 had no effect on the expression of a MG-induced CPP. The findings of this study suggested a crucial role of the DA D1 receptor in the acquisition, but not the expression of the rewarding effects of MG in a CPP test. Furthermore, blockade of the D1-like receptor during conditioning did not prevent MG priming effects on CPP reinstatement test, suggesting no role for the DA D1 receptor in reinstatement sensitivity.
Article
Introduction: Chronic neuropathic pain is as a severe detriment to overall quality of life for millions of Americans. Current pharmacological treatment options for chronic neuropathic pain are generally limited in efficacy and may pose serious adverse effects such as risk of abuse, nausea, dizziness, and cardiovascular events. Therefore, many individuals have resorted to methods of pharmacological self-treatment. This narrative review summarizes the existing literature on the utilization of two novel approaches for the treatment of chronic pain, cannabinoid constituents of Cannabis sativa and alkaloid constituents of Mitragyna speciosa (kratom), and speculates on the potential therapeutic benefits of co-administration of these two classes of compounds. Methods: We conducted a narrative review summarizing the primary motivations for use of both kratom and cannabis products based on epidemiological data and summarize the pre-clinical evidence supporting the application of both kratom alkaloids and cannabinoids for the treatment of chronic pain. Data collection was performed using the PubMed electronic database. The following word combinations were used: kratom and cannabis, kratom and pain, cannabis and pain, kratom and chronic pain, and cannabis and chronic pain. Results: Epidemiological evidence reports that the self-treatment of pain is a primary motivator for use of both kratom and cannabinoid products among adult Americans. Further evidence shows that use of cannabinoid products may precede kratom use, and that a subset of individuals concurrently uses both kratom and cannabinoid products. Despite its growing popularity as a form of self-treatment of pain, there remains an immense gap in knowledge of the therapeutic efficacy of kratom alkaloids for chronic pain in comparison to that of cannabis-based products, with only three pre-clinical studies having been conducted to date. Conclusion: There is sufficient epidemiological evidence to suggest that both kratom and cannabis products are used to self-treat pain, and that some individuals actively use both drugs, which may produce potential additive or synergistic therapeutic benefits that have not yet been characterized. Given the lack of pre-clinical investigation into the potential therapeutic benefits of kratom alkaloids against forms of chronic pain, further research is warranted to better understand its application as a treatment alternative.
Article
Penenelitian ini bertujuan menganalisis narasi yang dibangun BNN terkait dengan kebijakan kratom serta hambatan narasi kebijakan pelarangan kratom di Indonesia. Untuk menganalisis kebijakan tersebut, peneliti menggunakan metode analisis kebijakan publik (NPA). Yaitu, metode analisis dengan menggunakan kajian narasi terdiri dari level analisis, latar belakang serta plot dan pesan moral yang ingin disampaikan dalam narasi kebijakan. Model analisis ini juga digunakan peneliti untuk menganalisis isi narasi kebijakan khususnya mengenai nilai dan strategi untuk menyampaikan kebijakan pelarangan kratom. Hasil dalam penelitian ini menemukan adanya perbedaan antara kebijakan mengenai kratom yang dilakukan oleh BNN dan kebijakan yang dibuat oleh Kementerian/Lembaga serta Pemerintah Daerah penghasil tanaman kratom. Perbedaan kebijakan inilah yang akhirnya menghambat proses regulasi kratom masuk dalam UU No. 35 Tahun 2009 tentang narkotika.
Article
Ethnopharmacological relevance: The use of herbal tea infusions is widespread in ethnomedicine throughout the world. One such ethnobotanical is kratom (Mitragyna speciosa Korth., Rubiaceae) which has gained considerable interest as an herbal supplement in recent years in the West beyond its native Southeast Asia. Traditional, kratom leaves are either chewed fresh or made into a tea infusion to treat fatigue, pain, or diarrhea. However, dried kratom leaf powder and hydroalcoholic extracts are more commonly used in Western countries, raising the question of exposure to kratom alkaloids and related effects. Aim of the study: A specific kratom tea bag product was analyzed for mitragynine content using tea infusion preparation and methanolic extraction. Consumers of both the tea bag product and other kratom products completed an online anonymous survey to determine demographics, kratom use patterns, and self-reported beneficial and detrimental effects. Materials and methods: Kratom tea bag samples were extracted using pH-adjusted water or methanol and analyzed using an established LC-QTOF method. A modified kratom survey was distributed to consumers of the kratom tea bag products and other kratom products over a 14-month period. Results: Tea infusion extraction of tea bag samples resulted in lower mitragynine levels (0.062-0.131% (w/w)) compared to methanolic extraction (0.485-0.616% (w/w)). Kratom tea bag consumers did report similar, although often milder beneficial effects compared to consumers using other kratom products. Overall self-reported health was better among kratom tea bag consumers whereas improvement of a diagnosed medical condition was less in tea bag consumers compared to those using other kratom products. Conclusions: Traditional tea infusions of Mitragyna speciosa dried leaves provide benefits to consumers despite substantially lower mitragynine content. These effects may be less pronounced but indicate that tea infusions provide a potentially safer formulation compared to more concentrated products.
Article
Zusammenfassung Der Kratom-Baum, Mitragyna speciosa Korth., ist in feuchten Tieflandwäldern der Malaiischen Halbinsel und auf dem Malaiischen Archipel verbreitet. Die Blätter wurden volksmedizinisch bei Bluthochdruck, Durchfall, Husten oder Fieber verwendet. Aufgrund opioidartiger Effekte besitzt die Pflanze in asiatischen Ländern wie Thailand und Malaysia eine lange Nutzungsgeschichte. Die frischen Blätter werden als anregendes Genussmittel gekaut oder als Teeaufguss getrunken. Phytochemische Untersuchungen führten zur Isolierung von iridoiden Indolalkaloiden wie Mitragynin; neben den Alkaloiden sind Flavonoide, Kaffeesäurederivate, Monoterpene und Triterpenglykoside enthalten. Moderne In-vitro-Untersuchungen belegen eine Interaktion verschiedener Alkaloide mit Opioid-Rezeptoren, tierexperimentelle Befunde deuten auf eine analgetische und möglicherweise antidepressive/anxiolytische Wirkung hin. Klinische Studien zur Wirksamkeit der Blattdroge liegen bisher nicht vor.
Article
Background: Mitragyna speciosa or Kratom has been used in Thailand traditionally for its medicinal value. Despite case reports of kratom consumption causing adverse effects, research on its long-term health impact is limited. This study examines the long-term health impact of kratom use among people in Southern Thailand. Methods: Three community-based surveys were conducted from 2011 to 2015. In the first and second surveys (2011 and 2012) a total of 1,118 male respondents comprising 355 regular kratom users, 171 occasional kratom users, 66 ex-users, and 592 non-users aged 25 or above, were recruited from 40 villages. All respondents were followed up in this study. However, not all respondents were successfully followed up throughout the entire set of studies. Results: Common health complaints were no more common among kratom users than ex- and non-users, but more regular than occasional users claimed kratom to be addictive. Those with high kratom dependence scores were more likely to experience intense withdrawal symptoms, which developed 1-12 h after the last kratom intake. Over half (57.9%) of regular users had experienced intoxication effects compared to only 29.3% of occasional users. Kratom users were less likely to have a history of chronic diseases such as diabetes, hypertension, dyslipidemia than ex- and non-users. Conclusion: Regular long-term chewing of fresh kratom leaves was not related to an increase in common health complaints, but may pose a drug dependence risk. Severe kratom dependents were more likely to suffer from intense withdrawal symptoms. Medical records revealed no death due to traditional kratom use, but the high prevalence of tobacco or/and hand rolled cigarette smoking among kratom users should be of concern.
Article
The opioid epidemic and limited access to treatment for opioid withdrawal (OW) and opioid use disorder (OUD) has led individuals to seek alternative treatments. This narrative review aims to educate clinicians on the mechanisms of action, toxicity, and applications of psychoactive plant-based substances patients may be using to self-treat OUD and OW. We specifically discuss ayahuasca, ibogaine, and kratom as they have the most evidence for applications in OUD and OW from the last decade (2012-2022). Evidence suggests these substances may have efficacy in treating OW and OUD through several therapeutic mechanisms including their unique pharmacodynamic effects, rituals performed around ingestion, and increased neuroplasticity. The current evidence for their therapeutic application in OUD and OW is primarily based on small observational studies or animal studies. High-quality, longitudinal studies are needed to clarify safety and efficacy of these substances in treatment of OW and OUD.
Article
Mitragynine, an opioidergic alkaloid present in Mitragyna speciosa (kratom), is metabolized by cytochrome P450 3A (CYP3A) to 7-hydroxymitragynine, a more potent opioid receptor agonist. The extent to which conversion to 7-hydroxymitragynine mediates the in vivo effects of mitragynine is unclear. The current study examined how CYP3A inhibition (ketoconazole) modifies the pharmacokinetics of mitragynine in rat liver microsomes in vitro The study further examined how ketoconazole modifies the discriminative stimulus and antinociceptive effects of mitragynine in rats. Ketoconazole (30 mg/kg, o.g.) increased systemic exposure to mitragynine (13.3 mg/kg, o.g.) by 120% and 7-hydroxymitragynine exposure by 130%. The unexpected increase in exposure to 7-hydroxymitragynine suggested that ketoconazole inhibits metabolism of both mitragynine and 7-hydroxymitragynine, a finding confirmed in rat liver microsomes. In rats discriminating 3.2 mg/kg morphine from vehicle under a fixed-ratio schedule of food delivery, ketoconazole pretreatment increased the potency of both mitragynine (4.7-fold) and 7-hydroxymitragynine (9.7-fold). Ketoconazole did not affect morphine's potency. Ketoconazole increased the antinociceptive potency of 7-hydroxymitragynine 4.1-fold. Mitragynine (up to 56 mg/kg, i.p.) lacked antinociceptive effects both in the presence and absence of ketoconazole. These results suggest that both mitragynine and 7-hydroxymitragynine are cleared via CYP3A, and that 7-hydroxymitragynine is formed as a metabolite of mitragynine by other routes. These results have implications for kratom use in combination with numerous medications and citrus juices that inhibit CYP3A. Significance Statement Mitragynine is an abundant kratom alkaloid that exhibits low efficacy at the µ-opioid receptor (MOR). Its metabolite, 7-hydroxymitragynine, is also a MOR agonist but with higher affinity and efficacy than mitragynine. Our results in rats demonstrate that CYP3A inhibition can increase the systematic exposure of both mitragynine and 7-hydroxymitragynine and their capacity to produce MOR-mediated behavioral effects. These data highlight potential interactions between kratom and CYP3A inhibitors, which include numerous medications and even citrus juices.
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1. Zusammenfassung 1.1. Hintergrund und Ziele Alkoholismus ist eine schwerwiegende, in Deutschland und weltweit verbreitete Erkrankung mit physischen, psychischen und sozialen Symptomen, welche die Lebensqualität und Lebenserwartung der Betroffenen deutlich reduziert. Aktuelle Therapiekonzepte erfordern ein hohes Maß an Mitarbeit der Patienten, sind langwierig und erzielen oft auf Dauer nicht ihren gewünschten Erfolg. Zum jetzigen Zeitpunkt besitzen in Deutschland nur drei Medikamente ihre Zulassung als Mittel der pharmakologischen Therapie bei Alkoholabhängigkeit. Zwei dieser Pharmaka entfalten ihre Wirkung im Bereich des opioidergen Systems des Körpers. Auch Mitragynin, eines der Hauptalkaloide der Blätter des Kratombaumes, wirkt, wie in zahlreichen Studien nachgewiesen, unter anderem auf Opioidrezeptoren. Vor diesem Hintergrund befasst sich die vorliegende Arbeit nun mit der Frage, wie sich Mitragynin auf den Alkoholkonsum einer Gruppe männlicher Mäuse auswirkt und ob ein möglicher rückfallprophylaktischer Effekt nachgewiesen werden kann. 1.2. Methoden Für das Experiment wurden 14 männliche C57/BL6 Mäuse über einen Versuchszeitraum von 105 Tagen gemeinsam in einem IntelliCage® der Firma TSE Systems GmbH gehalten. An zwei Stunden pro Tag hatten sie begrenzt Zugang zu Alkohol in langsam ansteigender Konzentration (3 Vol.-%, 6 Vol.-%, 12 Vol.-% jeweils vier Tage, bis 20 Vol.-% 29 Tage), in den restlichen 22 Stunden erhielten sie Wasser ad libitum. Nach einer Alkoholtrinketablierung von 28 Tagen erfolgte jeweils für drei Tage die einmal tägliche Behandlung mittels intraperitonealer (i.p.) Injektion der Tiere, geteilt in zwei Gruppen mit einer 5 mg/kg Körpergewicht Mitragyninlösung einerseits und einem Vehikel (Kontrolllösung) andererseits. Die Injektionszeitpunkte wurden so gewählt, dass die Anwendungen einmal während des akuten Trinkens ohne Entzugserfahrung und einmal während des Entzugs vor dem Wiedereinsetzten des Trinkens stattfanden, um festzustellen, ob Mitragynin den Alkoholkonsum in den jeweiligen Paradigmen reduzieren kann. Während der Behandlungsdauer wurden das Körpergewicht [g], der Alkoholkonsum [g/kg/2 Stunden] und der Wasserkonsum [ml/kg/22 Stunden] der Tiere pro Tag gemessen, ausgewertet und dokumentiert. 1.3. Ergebnisse und Beobachtungen Die Resultate des Experiments zeigen, dass bei der Anwendung von Mitragynin während des akuten Trinkens eine hochsignifikante Reduktion des Alkoholkonsums im Vergleich zur Kontrollgruppe zu verzeichnen ist, was auf einen trinkmengenreduzierenden Effekt von Mitragynin hinweist. Der Wasserkonsum während der Behandlungszeit zeigte keine erwähnenswerten Unterschiede, rein in den Postbehandlungstagen stieg der Wasserkonsum in der Mitragynin-Gruppe signifikant in einem nicht besorgniserregenden Rahmen an. Kein signifikanter Unterschied im Alkoholkonsum konnte hingegen bei der Anwendung von Mitragynin während des Entzugs vor dem Wiedereinsetzen des Trinkens nachgewiesen werden. Auch der Wasserkonsum blieb in diesem Paradigma im Vergleich zur Kontroll-Gruppe unverändert. Diese Ergebnisse weisen darauf hin, dass Mitragynin wohl keine rückfallprophylaktischen Effekte erzielen kann. 1.4. Schlussfolgerungen und Diskussion Die Beobachtungen dieser Studie bekräftigen die Hypothese, dass der Einsatz von Mitragynin den Alkoholkonsum im akuten Stadium der Alkoholabhängigkeit im Mausmodell reduzieren kann. Somit wäre ein therapeutischer Einsatz bei Patienten ohne Entzugserfahrungen zur Reduktion der Trinkmenge denkbar. Zuvor bedarf es jedoch noch einiger tierexperimenteller und klinischer Studien, um bleibende offene Fragen über den genauen Wirkmechanismus von Mitragynin an den verschiedenen Rezeptoren zu beantworten.
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Kratom, an herbal substance with stimulant and opioid-like effects commonly used in capsules or powder to be ingested or brewed as a tea, has been gaining popularity in the United States (US). US e-cigarette use (i.e., vaping) has exponentially increased in recent years. Given the potential risks of kratom (e.g., poisonings) and the increasing prevalence of e-cigarette use, understanding the association between them is important to inform prevention strategies and regulatory policies. We harnessed data from the 2020 National Survey on Drug Use and Health (NSDUH; n = 27,170) to examine past-year kratom use by past-year e-cigarette use among adults. We ran a logistic regression model on kratom use by e-cigarette use adjusting for associated factors with substance use. Among all respondents, the estimated prevalence of past-year kratom use was 0.9% and an estimated 9.7% reported past-year e-cigarette use. Our multivariable model found those with e-cigarette use (vs. not) had 4.80 higher odds of using kratom in the past year (aOR = 4.80; 95% CI = 2.62, 8.80). These findings might help inform the need for continuing education for physicians and healthcare providers related to practice in managing patients with kratom use, future studies for regulatory policies on e-cigarettes (e.g., e-liquids), or other FDA policies related to kratom.
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Background Kratom, a psychoactive substance, use is an evolving research area that needs more studies to augment the limited literature. Our study examines the association between kratom use categories and mental health and substance use disorders in the U.S. population. Methods We used the 2020 National Survey on Drug Use and Health data (N = 32,893), a cross-sectional survey data, on the U.S. population aged 12 years or older. We used STATA/SE version 16 to perform a multinomial logistic regression analysis to assess our study aims. Results Bisexuals, compared to heterosexuals, had higher risks of kratom use within the past 30 days (relative risk ratio [RRR]= 2.47, 95% CI= 1.07, 5.71). Major depressive episode was positively associated with kratom use more than 30 days ago (RRR= 2.04, 95% CI= 1.24, 3.34). This association was also observed for mild (RRR= 2.04, 95% CI= 1.38, 3.02), moderate (RRR= 2.25, 95% CI= 1.13, 4.51), or severe alcohol use disorder (RRR= 1.88, 95% CI= 1.05, 3.36); and mild (RRR= 1.98, 95% CI= 1.27, 3.11), moderate (RRR= 2.38, 95% CI= 1.27, 4.45), or severe marijuana use disorder (RRR= 2.13, 95% CI= 1.02, 4.47). Illicit drug other than marijuana use disorder was associated positively with kratom use more than 30 days ago (RRR= 2.81, 95% CI= 1.85, 4.26) and kratom use within the past 30 days (RRR= 5.48, 95% CI= 1.50, 20.02). Conclusions Our findings suggested that identifying as bisexual, experiencing depression, alcohol use disorder, or illicit drug use disorder increased the risks of kratom use. There is a need to consider mental health and substance use disorders and sexual identity in kratom use interventions and policies geared toward reducing or preventing kratom use.
Article
Background Kratom (Mitragyna speciosa korth), has been used traditionally in Southeast Asia for its therapeutic properties. The major alkaloid of kratom, mitragynine binds to opioid receptors to give opioid‐like effects that causes addiction. In our previous study, we have identified AZ122 as a unique biomarker in habitual or regular kratom users through analysis of their urinary protein profiles. We aimed to develop and validate a screening method by means of ELISA for detection of kratom habitual users. Methods An ELISA approach was applied for the development of a screening method using urinary AZ122 as biomarker. Method validation was carried out using 3 QC materials at different concentration of AZ122. The data was analyzed statistically using SPSS (Version 25). Results The ELISA was presented with Pearson correlation coefficient of 0.9993. The repeatability and reproducibility were presented at CV <7%, while the accuracy ranged from 78% to 96% at various AZ112 concentrations. Upon testing on 176 male respondents (n = 88 regular kratom users, and n = 88 healthy controls), the specificity and sensitivity of the assay were both 100%. Conclusions The ELISA has been validated and can be potentially used as a reliable screening test for detection of kratom habitual users.
Article
Background Substance use has been strongly liked to psychosis, though less is known about illicit/prescription drug use and its relation to psychotic experiences among college students. Methods We analyzed data from the 2020-2021 Cohort of the Healthy Minds Study (September 2020 – June 2021), which was an online survey administered across 140 college campuses in the United States. Multivariable logistic regression models showed the associations between each illicit/prescription drug and 12-month psychotic experiences, adjusting for socio-demographic characteristics, as well as alcohol, tobacco, and marijuana use. Results Nearly one-in-six of the sample reported psychotic experiences over the past year, and approximately 4% reported misusing any illicit or prescription drug over the past month. Separate multivariable logistic regression models showed that each drug was associated with greater odds of having psychotic experiences. The associations between drug use and psychotic experiences persisted even after adjustment for alcohol, tobacco, and marijuana use, though the relationships with heroin and methamphetamine use were statistically insignificant. The count of substances was associated with increased odds of psychotic experiences in a dose-response relation. Conclusion Use of several illicit and prescription drugs was associated with psychotic experiences, even when accounting for alcohol, tobacco, and marijuana use.
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Kratom (Mitragyna speciosa) is a psychoactive plant that has been used since at least 1836 in folk medicine in Southeast Asian countries. More recently, kratom has become widely available in the West and is used for both recreational and medicinal purposes. There has, however, been little scientific research into the short- and long-term effects of kratom in humans, and much of the information available is anecdotal. To supplement the increasing scientific understanding of kratom's pharmacology and research into its effects in animals, we report the results of a qualitative analysis of first-hand descriptions of human kratom use that were submitted to, and published by, a psychoactive substance information website (Erowid.org). Themes that emerged from these experience reports indicate that kratom may be useful for analgesia, mood elevation, anxiety reduction, and may aid opioid withdrawal management. Negative response themes also emerged, indicating potential problems and unfavorable "side" effects, especially stomach upset and vomiting. Based on our analyses, we present preliminary hypotheses for future examination in controlled, quantitative studies of kratom.
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The use of substances to enhance human abilities is a constant and cross-cultural feature in the evolution of humanity. Although much has changed over time, the availability on the Internet, often supported by misleading marketing strategies, has made their use even more likely and risky. This paper will explore the case of Mitragyna speciosa Korth. (kratom), a tropical tree used traditionally to combat fatigue and improve work productivity among farm populations in Southeast Asia, which has recently become popular as novel psychoactive substance in Western countries. Specifically, it (i) reviews the state of the art on kratom pharmacology and identification; (ii) provides a comprehensive overview of kratom use cross-culturally; (iii) explores the subjective experiences of users; (iv) identifies potential risks and side-effects related to its consumption. Finally, it concludes that the use of kratom is not negligible, especially for self-medication, and more clinical, pharmacological, and socioanthropological studies as well as a better international collaboration are needed to tackle this marginally explored phenomenon.
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Kratom (Mitragyna speciosa) is an indigenous plant known for its traditional medicinal use, and for its addiction potential, in Southeast Asia. In recent years, kratom and its major alkaloid, mitragynine, spread worldwide with largely unknown effects on behavior and mental health. Recent studies show that kratom use can lead to dependence and that mitragynine works as an addictive drug in animal studies. Nevertheless, kratom preparations were also suggested as a less harmful substitute in opiate withdrawal. Potential side-effects of prolonged kratom use, however, are currently unclear. The aim of this study was to investigate the social functioning of regular kratom users in Malaysia. A cross-sectional survey was carried out in three northern states of Peninsular Malaysia investigating 293 regular kratom consumers using the Addiction Severity Index in a snowball sampling technique. Findings showed that regular kratom users do not experience major impairments in their social functioning, despite being dependent on kratom for prolonged periods. Our findings suggest that chronic kratom administration does not significantly impair social functioning of users in a natural context in Malaysia.
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A 24-year-old man whose medical history was significant for alcohol abuse and depression was found unresponsive in bed. He had several prior suicide attempts with 'pills' and had also been hospitalized for an accidental overdose on a previous occasion. Autopsy findings were unremarkable apart from pulmonary edema and congestion, and urinary retention. Postmortem peripheral blood initially screened positive for mitragynine 'Kratom' (by routine alkaline drug screen by gas chromatography-mass spectrometry, GC-MS), which was subsequently confirmed by a specific GC-MS selective ion mode analysis following solid-phase extraction. Concentrations were determined in the peripheral blood (0.23 mg/L), central blood (0.19 mg/L), liver (0.43 mg/kg), vitreous (<0.05 mg/L), urine (0.37 mg/L) and was not detected in the gastric. Therapeutic concentrations of venlafaxine, diphenhydramine and mirtazapine were also detected together with a negligible ethanol of 0.02% (w/v). The results are discussed in relation to previous cases of toxicity, and the lack of potential for mitragynine postmortem redistribution. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Mood disorders are devastating, often chronic illnesses characterized by low mood, poor affect, and anhedonia. Notably, mood disorders are approximately twice as prevalent in women compared to men. If sex differences in mood are due to underlying biological sex differences, a better understanding of the biology is warranted to develop better treatment or even prevention of these debilitating disorders. In this review, our goals are to: 1) summarize the literature related to mood disorders with respect to sex differences in prevalence, 2) introduce the corticolimbic brain network of mood regulation, 3) discuss strategies and challenges of modeling mood disorders in mice, 4) discuss mechanisms underlying sex differences and how these can be tested in mice, and 5) discuss how our group and others have used a translational approach to investigate mechanisms underlying sex differences in mood disorders in humans and mice.
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Background: Krathom (Mitragyna speciosa Korth.) is the most commonly used illicit substance in Thailand, and its use has become widespread internationally. Studies on krathom dependence and its health impact are scarce, as there has been no instrument to measure its dependence syndrome and classify krathom users. This study aimed to develop and explore the factor structure, reliability, and validity of a Krathom Dependence Scale (KDS). Methods: This study comprised 2 phases. First, cross-sectional surveys were conducted with 523 (Phase I) and 595 (Phase II) male villagers aged >25 years who were regular, occasional, ex-, or nonusers of krathom. Scale construction was based on the qualitative results from users and previous literature. Exploratory factor analysis (EFA) using maximum likelihood extraction with oblimin rotation was conducted in Phase I and confirmatory factor analysis (CFA) in Phase II to confirm the construct of the scale. Internal consistency of the KDS was assessed using Cronbach's alpha coefficient. Discriminative validity was examined by checking its ability to differentiate between regular and occasional users and patterns of krathom use and its concurrent validity by comparing its levels of score with the Fagerstrom Test for Nicotine Dependence (FTND). The KDS contains 16 items on a 0-3 (never-always) rating scale, making a total score of 0-48. Results: Phase I EFA revealed a single-factor solution for the scale, which was confirmed by the CFA in Phase II, with an alpha coefficient of .98. The KDS discriminates regular from occasional users reasonably well and is highly correlated with the FTND score. Two cutoffs were suggested: 34/35 for distinguishing moderate from high dependence and 13/14 for low from moderate. Conclusions: The KDS appears to capture key theoretical constructs and correlates with indices of drug dependence by standard criteria. It should be useful in early intervention for those with krathom use disorders in community and primary care settings.
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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.
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Reports of toxicity secondary to Kratom are rare and lack of diagnostic testing in human specimens has prevented confirmatory explanation of observed clinical effects. We present a novel case of serious human toxicity following Kratom use confirmed via quantitative analysis of urine by high performance liquid chromatography coupled to electrospray tandem mass spectrometry. A 64 year-old male was witnessed to have a seizure at home following kratom consumption. Upon arrival to the emergency department (ED), the patient was unresponsive. While in the ED, the patient sustained a second seizure. He was intubated to protect his airway. The remainder of his hospital course was uneventful. A urine specimen was collected shortly after admission and sent for analysis. The mitragynine concentration in the urine was 167 ± 15 ng/ml. We report a rare case of Kratom toxicity characterized by a seizure and coma confirmed by urinary analysis of mitragynine by high performance liquid chromatography coupled to electrospray tandem mass spectrometry. The proposed mechanism for this reaction is unclear but suggested mechanisms include adenosine binding or stimulation of adrenergic and/or serotonergic receptors similar to tramadol.
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Some people who take selective serotonin reuptake inhibitor (SSRI) antidepressants report that their experience of emotions is 'blunted'. This phenomenon is poorly understood. To understand patients' experiences of this phenomenon. Qualitative study, gathering data through individual interviews, a group interview and validation interviews; and searching patient websites for relevant posts. There was strong evidence that some people taking SSRIs experience significant emotional symptoms that they strongly attribute to their antidepressant. These emotional symptoms can be described within six key themes. A seventh theme represents the impact of these side-effects on everyday life, and an eighth represents participants' reasons for attributing these symptoms to their antidepressant. Most participants felt able to distinguish between emotional side-effects of antidepressants and emotional symptoms of their depression or other illness. Emotional side-effects of SSRIs are a robust phenomenon, prominent in some people's thoughts about their medication, having a demonstrable impact on their functioning and playing a role in their decision-making about antidepressant adherence.
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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.
Article
Background: Finding an effective, non-pharmacological approach to treat opioid withdrawal could remove some of the barriers associated with pharmacotherapy. The BRIDGE® is a noninvasive, percutaneous electrical nerve field stimulator developed to target pain. Objectives: This pilot study aimed to determine (1) the effects of the BRIDGE on withdrawal scores during the induction phase of opioid withdrawal therapy, (2) the percentage of subjects who successfully transitioned to medication assisted therapy (MAT). Methods: Adult patients treated with the BRIDGE during medically supervised withdrawal were included in this open label, uncontrolled, and retrospective study. The clinical opioid withdrawal scale (COWS) scores were prospectively recorded at different intervals (20, 30, and 60 min) and analyzed retrospectively. A subset of patients had scores recorded 5-days post-BRIDGE. Those who returned to the clinic and received their first dose of maintenance medication were considered to be successfully transitioned. Results: In this cohort (n=73), 65% were male. The mean COWS score prior to BRIDGE placement was 20.1 (±6.1). Twenty minutes after BRIDGE placement, the mean score was reduced to 7.5 (±5.9) (62.7% reduction, p<0.001). The scores further decreased after 30 minutes 4.0 (±4.4) and 60 minutes 3.1 (±3.4) (84.6% reduction, p<0.001). No rescue medications were administered during this period. The mean withdrawal score on day 5 was 0.6 (97.1% reduction, p<0.001) (n=33). Overall, 64/73 patients (88.8%) successfully transitioned to MAT. Conclusions: Neurostimulation with the BRIDGE is associated with a reduction in opioid withdrawal scores. This effect persisted during the induction period and allowed for effective transition to MAT.
Article
Objectives: The aim of this study is to review the effectiveness of third wave mindfulness-based cognitive behavioral therapies (CBTs) for depressive or anxiety symptomatology in older adults across a wide range of physical and psychological conditions. Methods: Electronic literature databases were searched for articles, and random-effects meta-analysis was conducted. Results: Ten studies met the inclusion criteria, of which nine reported the efficacy of interventions on depressive symptoms and seven on anxiety symptoms. Effect-size estimates suggested that mindfulness-based CBT is moderately effective on depressive symptoms in older adults (g = 0.55). The results demonstrated a similar level of overall effect size for anxiety symptoms (g = 0.58). However, there was a large heterogeneity, and publication bias was evident in studies reporting outcomes on anxiety symptoms, and thus, this observed efficacy for late-life anxiety may not be robust. The quality of the included studies varied. Only one study used an active psychological control condition. There were a limited number of studies that used an intent-to-treat (last observation carried forward method) analysis and reported appropriate methods for clinical trials (e.g., treatment-integrity reporting). Conclusions: Third wave mindfulness-based CBT may be robust in particular for depressive symptoms in older adults. We recommend that future studies (i) conduct randomized controlled trials with intent-to-treat to compare mindfulness-based CBT with other types of psychotherapy in older people and (ii) improve study quality by using appropriate methods for checking treatment adherence, randomization, and blinding of assessors. Copyright © 2016 John Wiley & Sons, Ltd.
Article
This review considers the potential influences of the use of cannabis for therapeutic purposes (CTP) on areas of interest to mental health professionals, with foci on psychological intervention and assessment. We identified 31 articles relating to CTP use and mental health, and 29 review articles on cannabis use and mental health that did not focus on use for therapeutic purposes. Results reflect the prominence of mental health conditions among the reasons for CTP use, and the relative dearth of high-quality evidence related to CTP in this context, thereby highlighting the need for further research into the harms and benefits of medical cannabis relative to other therapeutic options. Preliminary evidence suggests that CTP may have potential for the treatment of PTSD, and as a substitute for problematic use of other substances. Extrapolation from reviews of non-therapeutic cannabis use suggests that the use of CTP may be problematic among individuals with psychotic disorders. The clinical implications of CTP use among individuals with mood disorders are unclear. With regard to assessment, evidence suggests that CTP use does not increase risk of harm to self or others. Acute cannabis intoxication and recent CTP use may result in reversible deficits with the potential to influence cognitive assessment, particularly on tests of short-term memory.
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
Introduction: The objective of the paper was to highlight the differences in the traditional and non-traditional users of kratom in the South East Asian and Western contexts. Method: A literature survey of published kratom studies among humans was conducted. Forty published studies relevant to the objective were reviewed. Results: Apart from the differences in the sources of supply, patterns of use and social acceptability of kratom within these two regions, the most interesting finding is its evolution to a recreational drug in both settings and the severity of the adverse effects of kratom use reported in the West. While several cases of toxicity and death have emerged in the West, such reports have been non-existent in South East Asia where kratom has had a longer history of use. We highlight the possible reasons for this as discussed in the literature. More importantly, it should be borne in mind that the individual clinical case-reports emerging from the West that link kratom use to adverse reactions or fatalities frequently pertained to kratom used together with other substances. Therefore, there is a danger of these reports being used to strengthen the case for legal sanction against kratom. This would be unfortunate since the experiences from South East Asia suggest considerable potential for therapeutic use among people who use drugs. Conclusion: Despite its addictive properties, reported side-effects and its tendency to be used a recreational drug, more scientific clinical human studies are necessary to determine its potential therapeutic value.
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
As a result of the prescription opioid epidemic in the United States, there has been an increasing need for effective treatment interventions, both pharmacological and nonpharmacological. Buprenorphine has emerged as a critical component of the treatment of opioid use disorder, yet its adoption has not been without some concerns. This article first reviews the pharmacology, clinical use, and US legislative action related to buprenorphine, followed by a discussion of the misuse and diversion of buprenorphine in the United States as well as internationally. We then explore the impact of buprenorphine abuse as well as discussing strategies for its reduction, including changes in policy, prescription and pharmacy monitoring, and continuing medical education for guiding and improving clinical practice.
Article
Krathom (Mitragyna speciosa Korth.) is an addictive and illicit substance used in Thailand and other Southeast Asian countries. It has become the most commonly used substance among villagers. The study aimed to explore the factor structure of the krathom withdrawal syndrome based on the findings of an earlier qualitative study. The current study was divided into two stages. Cross-sectional data collections were employed in both phases. The samples comprised, respectively, 196 and 330 krathom users aged over 25 years. The characteristics of krathom withdrawal symptoms and signs were identified and the factor structure examined using exploratory factor analysis (EFA). Confirmatory Factor Analysis (CFA) was used to examine the construct validity and multivariate linear regression was used to identify factors predicting the intensity of krathom withdrawal symptoms. The final scale comprised 20 items with four factors: craving-fatigue syndrome; musculoskeletal system and insomnia; mood symptoms; and autonomic nervous system/physical sickness. Symptoms and signs of krathom withdrawal similar to those of the withdrawal syndrome of opioid substances appear to be present in regular krathom users. The krathom withdrawal intensity is predicted by duration of krathom use, frequency, and daily amount of krathom use.
Article
Importance Opioid analgesic overdose mortality continues to rise in the United States, driven by increases in prescribing for chronic pain. Because chronic pain is a major indication for medical cannabis, laws that establish access to medical cannabis may change overdose mortality related to opioid analgesics in states that have enacted them.Objective To determine the association between the presence of state medical cannabis laws and opioid analgesic overdose mortality.Design, Setting, and Participants A time-series analysis was conducted of medical cannabis laws and state-level death certificate data in the United States from 1999 to 2010; all 50 states were included.Exposures Presence of a law establishing a medical cannabis program in the state.Main Outcomes and Measures Age-adjusted opioid analgesic overdose death rate per 100 000 population in each state. Regression models were developed including state and year fixed effects, the presence of 3 different policies regarding opioid analgesics, and the state-specific unemployment rate.Results Three states (California, Oregon, and Washington) had medical cannabis laws effective prior to 1999. Ten states (Alaska, Colorado, Hawaii, Maine, Michigan, Montana, Nevada, New Mexico, Rhode Island, and Vermont) enacted medical cannabis laws between 1999 and 2010. States with medical cannabis laws had a 24.8% lower mean annual opioid overdose mortality rate (95% CI, −37.5% to −9.5%; P = .003) compared with states without medical cannabis laws. Examination of the association between medical cannabis laws and opioid analgesic overdose mortality in each year after implementation of the law showed that such laws were associated with a lower rate of overdose mortality that generally strengthened over time: year 1 (−19.9%; 95% CI, −30.6% to −7.7%; P = .002), year 2 (−25.2%; 95% CI, −40.6% to −5.9%; P = .01), year 3 (−23.6%; 95% CI, −41.1% to −1.0%; P = .04), year 4 (−20.2%; 95% CI, −33.6% to −4.0%; P = .02), year 5 (−33.7%; 95% CI, −50.9% to −10.4%; P = .008), and year 6 (−33.3%; 95% CI, −44.7% to −19.6%; P < .001). In secondary analyses, the findings remained similar.Conclusions and Relevance Medical cannabis laws are associated with significantly lower state-level opioid overdose mortality rates. Further investigation is required to determine how medical cannabis laws may interact with policies aimed at preventing opioid analgesic overdose.
Article
Kratom (Mitragyna speciosa Korth), a native tree in Southeast Asia, is misused as an abuse drug and becomes legally widespread to several countries. Currently, it is available through the online market or by some shops. The clinical manifestations of Kratom's effects are not well-defined and the clinical studies are limited. This study was designed to identify the characteristics of Kratom poisoning and withdrawal cases from Kratom exposure cases in Ramathibodi Poison Center (RPC), Thailand, during a five-year period. We used a retrospective review of Kratom exposure cases from the RPC toxic surveillance system. A total of 52 Kratom exposure cases were identified. The trend of case consultations has been increasing. There were Kratom poisoning cases (76.9%) and withdrawal cases (23.1%). Common presenting symptoms in the poisoning group were palpitation (22.5%), followed by seizure (17.5%). For the withdrawal group, the common presenting symptoms were myalgia (33.3%), insomnia (16.67%), fatigue (16.67%), and chest discomfort (16.67%). There was a baby with withdrawal symptoms who was delivered from a chronic Kratom-abusing mother, suggesting possible exposure via the transplacental route. There were no deaths in either group. Kratom abuse can cause either poisoning or withdrawal. Most cases in both groups had good prognostic outcome.
Article
Kratom use is a growing problem in the United States. Kratom exposures reported to Texas poison centers between January 1998 and September 2013 were identified. No kratom exposures were reported from 1998 to 2008 and 14 exposures were reported from 2009 to September 2013. Eleven patients were male, and 11 patients were in their 20s. The kratom was ingested in 12 patients, inhaled in 1, and both ingested and inhaled in 1. Twelve patients were managed at a healthcare facility and the remaining 2 were managed at home.
Article
Background: Krathom is currently the most popular illicit substance in use in southern Thailand. Research regarding its effects and health impacts is scarce. This study explored the pattern of krathom use and users' perceptions of the consequences of its use. Methods: An in-depth qualitative interview. A group of 34 self-identified regular users, occasional users, non-users and ex-users of krathom was used in this study. Health volunteer as a key-contact person helped the researcher to invite villagers to participate in the study using snowballing technique. The process of data analysis was guided by Strauss and Corbin's grounded theory. Results: The core category, 'Understanding krathom use', was generated from three inter-related categories: (i) reasons for continuing krathom use, (ii) the way of applying krathom, and (iii) perceiving positive and realizing the negative effects of krathom use and their 18 subcategories. Conclusions: The study findings reveal the importance of considering krathom use from the perspective and belief of the villagers. Krathom is addictive with its own characteristic symptoms and signs. The results provide support for policy interventions to control the availability of krathom according to the community context. In addition, krathom misuse by adolescents must be considered.
Article
A 17-year-old white man who showed no obvious signs of trauma was found unresponsive in bed and was pronounced dead at the scene. The decedent had a documented history of heroin abuse and chronic back pain and reportedly self-medicated with Kratom (mitragynine). The autopsy was remarkable only for pulmonary congestion and edema and a distended bladder, both of which are consistent with, though not diagnostic of, opiate use. A laboratory work-up revealed therapeutic levels of over-the-counter cold medications and benzodiazepines. However, of interest was a level of mitragynine at 0.60 mg/L. Given the facts of the case, the Medical Examiner certified the cause of death as "possible Kratom toxicity" and the manner of death was classified as "accident."
Article
Striking increases in the abuse of opioids have expanded the need for pharmacotherapeutic interventions. The obstacles that confront effective treatment of opioid addiction - shortage of treatment professionals, stigma associated with treatment and the ability to maintain abstinence - have led to increased interest in alternative treatment strategies among both treatment providers and patients alike. Herbal products for opioid addiction and withdrawal, such as kratom and specific Chinese herbal medications such as WeiniCom, can complement existing treatments. Unfortunately, herbal treatments, while offering some advantages over existing evidence-based pharmacotherapies, have poorly described pharmacokinetics, a lack of supportive data derived from well controlled clinical trials, and severe toxicity, the cause for which remains poorly defined. Herbal products, therefore, require greater additional testing in rigorous clinical trials before they can expect widespread acceptance in the management of opioid addiction.
Article
Here we present a case of a coincidence of addiction to "Kratom" (botanically known as Mitragyna speciosa Korth) and developed severe primary hypothyroidism. We are discussing a possibility that high dose of indole alkaloid mitragynine (the major alkaloid identified from "Kratom") might reduce the normal response of the thyroid gland to thyroid-stimulating hormone resulting in primary hypothyroidism. Further experimental investigations of mitragynine as a possible suppressor of thyroid gland function would be a matter of interest.
Article
Kratom (Mitragyna speciosa) is a common medical plant in Thailand and is known to contain mitragynine as the main alkaloid. According to an increase in published reports and calls at German poison control centers, it has been used more frequently as a drug of abuse in the western hemisphere during the last couple of years. Despite this increase, reports of severe toxicity are rare within the literature. We describe a case of a young man who presented with jaundice and pruritus after intake of kratom for 2 weeks in the absence of any other causative agent. Alkaloids of M. speciosa were detected in the urine. While M. speciosa is gaining in popularity among illicit drug users, its adverse effects remain poorly understood. This is the first published case of intrahepatic cholestasis after kratom abuse.
Article
Ketum (krathom) has been mentioned in the literature as a traditional alternative to manage drug withdrawal symptoms though there are no studies indicating its widespread use for this purpose. This study examines the reasons for ketum consumption in the northern areas of peninsular Malaysia where it is widely used. A cross-sectional survey of 136 active users was conducted in the northern states of Kedah and Penang in Malaysia. On-site urine screening was done for other substance use. Ketum users were relatively older (mean 38.7 years) than the larger substance using group. Nearly 77% (104 subjects) had previous drug use history, whilst urine screening confirmed 62 subjects were also using other substances. Longer-term users (use >2 years) had higher odds of being married, of consuming more than the average three glasses of ketum a day and reporting better appetite. Short-term users had higher odds of having ever used heroin, testing positive for heroin and of using ketum to reduce addiction to other drugs. Both groups used ketum to reduce their intake of more expensive opiates, to manage withdrawal symptoms and because it was cheaper than heroin. These findings differ from those in neighbouring Thailand where ketum was used primarily to increase physical endurance. No previous study has shown the use of ketum to manage opioid withdrawal symptoms except for a single case reported in the US. Ketum was described as affordable, easily available and having no serious side effects despite prolonged use. It also permitted self-treatment that avoids stigmatisation as a drug dependent. The claims of so many subjects on the benefits of ketum merits serious scientific investigation. If prolonged use is safe, the potential for widening the scope and reach of substitution therapy and lowering its cost are tremendous, particularly in developing countries.
Article
Cognitive-behavioral therapy (CBT) is frequently used for various adult anxiety disorders, but there has been no systematic review of the efficacy of CBT in randomized placebo-controlled trials. The present study meta-analytically reviewed the efficacy of CBT versus placebo for adult anxiety disorders. We conducted a computerized search for treatment outcome studies of anxiety disorders from the first available date to March 1, 2007. We searched MEDLINE, PsycINFO, PubMed, Scopus, the Institute of Scientific Information, and Dissertation Abstracts International for the following terms: random*, cognitive behavior*therap*, cognitive therap*, behavior*therap*, GAD, generalized anxiety disorder, OCD, obsessive compulsive disorder, social phobia, social anxiety disorder, specific phobia, simple phobia, PTSD, post-traumatic stress disorder, and acute stress disorder. Furthermore, we examined reference lists from identified articles and asked international experts to identify eligible studies. We included studies that randomly assigned adult patients between ages 18 and 65 years meeting DSM-III-R or DSM-IV criteria for an anxiety disorder to either CBT or placebo. Of 1165 studies that were initially identified, 27 met all inclusion criteria. The 2 authors independently identified the eligible studies and selected for each study the continuous measures of anxiety severity. Dichotomous measures reflecting treatment response and continuous measures of depression severity were also collected. Data were extracted separately for completer (25 studies for continuous measures and 21 studies for response rates) and intent-to-treat (ITT) analyses (6 studies for continuous measures and 8 studies for response rates). There were no significant differences in attrition rates between CBT and placebo. Random-effects models of completer samples yielded a pooled effect size (Hedges' g) of 0.73 (95% CI = 0.88 to 1.65) for continuous anxiety severity measures and 0.45 (95% CI = 0.25 to 0.65) for depressive symptom severity measures. The pooled odds ratio for completer treatment response rates was 4.06 (95% CI = 2.78 to 5.92). The strongest effect sizes were observed in obsessive-compulsive disorder and acute stress disorder, and the weakest effect size was found in panic disorder. The advantage of CBT over placebo did not depend on placebo modality, number of sessions, or study year. Our review of randomized placebo-controlled trials indicates that CBT is efficacious for adult anxiety disorders. There is, however, considerable room for improvement. Also, more studies need to include ITT analyses in the future.
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.