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Kratom use and mental health: A systematic review
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.
... 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. ...
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. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
... 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]. ...
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. ...
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.
... The reported therapeutic benefits span improvement in psychiatric symptoms to self-treatment of pain or substance use disorder (SUD) symptoms (1,(14)(15)(16)(17). Despite its reported benefits, long-term and chronic (high dose) kratom consumption can induce the development of tolerance and withdrawal symptoms during discontinuation ( [18][19][20][21]. It is also documented that people may develop dependence from chronic kratom use (22,23), which is consistent with findings of a study of individuals who reported using kratom to address dependence on other substances and end up experiencing difficulty ceasing kratom use (24). ...
... In contrast to a large 2017 online survey among 8,049 US kratom consumers, a greater percentage of PWUK in this survey used kratom to mitigate or substitute for an illicit (17.7 vs 7.7%) or a prescription (38.7 vs 26.0%) drug or substance (3). The increased use of kratom for these indications may partially be attributed to the widespread media coverage in recent years highlighting kratom's opioid-like effects amidst the height of the US opioid crisis and studies supporting its potential therapeutic use as a harm reduction component or mitigation treatment of OUD, and potentially other SUDs (15,18,31,(34)(35)(36)(37), although respondents were not specifically asked about kratom use and media coverage. However, kratom consumption in the context of poly-substance use was also detected, with 5.2% of respondents reporting using kratom and other drugs concomitantly. ...
... Given the well-established analgesic effects of kratom and the opioid-like pharmacology of several of its alkaloids, the use of kratom in the self-treatment of pain has both traditional roots and modern uses. Kratom is also used for self-managing mental health symptoms such as anxiety and depression (3,18). Taking kratom for self-treatment of an emotional or psychiatric condition was preferred by females and younger consumers under the age of 41 who were not married, similar to the earlier survey conducted in 2017. ...
Background:
Kratom (Mitragyna speciosa Korth.) use outside of Southeast Asia has increased over the past decade.
Objectives:
This investigation clarifies kratom's role in perceived well-being, overall health, and temporal correlation with drug use to understand kratom's role in the self-treatment of substance use disorders (SUDs).
Methods:
Between July 2019 and July 2020 an anonymous, cross-sectional, online survey was taken by 7,381 people who use kratom (PWUK) recruited through social media and other online resources. This included an assessment of (a) the relationship between self-reported overall health, concomitant use of drugs of misuse, and demographics; (b) the perceived effectiveness of kratom in self-treating diagnosed health conditions or symptoms; (c) the profile of PWUK primarily for drug dependence, pain, and mood or mental health conditions based on demographics.
Results:
A total of 5,152 valid responses (45.9% females/53.7% males) were collected. Kratom was primarily used for self-treating pain (73.0%) and improving emotional or mental health conditions (42.2%) without clinical supervision. Those with a SUD (synthetic opioids, methadone, benzodiazepines, or heroin) used kratom after discontinuing illicit or other drugs (94.8%). The primary substances taken before or concomitantly with kratom were cannabis, cannabidiol, benzodiazepines, or kava. PWUKs report a dose-dependent benefit for alleviating pain and relieving negative moods. Adverse effects were primarily gastrointestinal, typically at high (>5 g/dose) and frequent (>22 doses/week) dosing.
Conclusions:
Kratom was primarily used as a harm-reduction agent for SUDs and self-treatment of chronic conditions. Healthcare professionals need better information about kratom, its potential adverse effects, and clinically significant drug interactions.
... Banning or criminalizing kratom, as six United States have done at the time of this writing, has the potential to create a new illicit market for kratom products, increasing the likelihood of adulteration and the use of dangerous substances as kratom substitutes. All of this results in harm to people who regularly use kratom to address pain, psychiatric problems, and SUD symptoms (Grundmann, 2017;Swogger and Walsh, 2018;Coe et al., 2019;Smith et al., 2021a;Smith et al., 2021b). Moreover, sensationalized and negative reports lead some patients to fear revealing kratom use to their healthcare providers (Smith et al., 2021b) and misinform those providers about the risks of kratom use. ...
... Kratom as a substitute to opioids also has the potential to improve social, family and occupational outcomes and behavior (Swogger et al., 2015;Henningfield et al., 2018;Swogger and Walsh, 2018). Like coffee drinkers, regular kratom users often consume this herbal supplement as a beverage in the company of others, enhancing social connection. ...
... Kratom tolerance, dependence, and withdrawal have been reported with daily and heavy use, though these symptoms are generally milder and of shorter duration than those of classical opioids (Ahmad and Aziz, 2012;Singh et al., 2014;Singh et al., 2015;Swogger et al., 2015;Grundmann, 2017;Swogger and Walsh, 2018;Smith et al., 2021b). Physical dependence that can develop over time has been described as similar to that of coffee or mild opioid dependence (Brown et al., 2017). ...
Kratom (Mitragyna speciosa Korth., Rubiaceae) is a plant native to Southeast Asia, where it has been used for centuries as a mild stimulant and as medicine for various ailments. More recently, as kratom has gained popularity in the West, United States federal agencies have raised concerns over its safety leading to criminalization in some states and cities. Some of these safety concerns have echoed across media and broad-based health websites and, in the absence of clinical trials to test kratom's efficacy and safety, considerable confusion has arisen among healthcare providers. There is, however, a growing literature of peer-reviewed science that can inform healthcare providers so that they are better equipped to discuss kratom use with consumers and people considering kratom use within the context of their overall health and safety, while recognizing that neither kratom nor any of its constituent substances or metabolites have been approved as safe and effective for any disease. An especially important gap in safety-related science is the use of kratom in combination with physiologically active substances and medicines. With these caveats in mind we provide a comprehensive overview of the available science on kratom that has the potential to i clarity for healthcare providers and patients. We conclude by making recommendations for best practices in working with people who use kratom.
... Описані такі ефекти: занепокоєння, дратівливість та підвищення агресивності. Тривале споживання високих доз кратому має специфічні ефекти: гіперпігментація щік, тремор, анорексія, втрата ваги, психози та прояви залежності [9,10,77]. Незважаючи на те, що використання кратому в ситуаціях відміни опіоїдів стало поширеним явищем, у науковій літературі описуються суттєві наслідки для здоров'я, а самесиндром відміни кратому. В умовах субхронічного експерименту доведено, що високі дози Mitragyna speciosa здатні викликати ураження легень (ознаки емфіземи) та нирок (підвищення рівня креатиніну та сечовини в крові) [61]. ...
... Effects such as anxiety, irritability and increased aggression have been described. Prolonged consumption of high doses of kratom has specific effects: cheek hyperpigmentation, tremor, anorexia, weight loss, psychosis and dependence [9,10,77]. ...
... Нині в усьому світі існує безліч продуктів під комерційною назвою «Kratom», які нерідко містять широкий спектр інших природних та синетичних речовин. За даними США, протягом 2016 року було вилучено близько 500 тонн кратому, що втричі перевищило таку кількість у попереньому році, що свідчить про небезпеку зростання популярності даного засобу та розширення спектру споживачів [77,78]. ...
Ukraine today does not regulate the sale of products made of Kratom (Mitragyna speciosa Korth. (from the family Rubiaceae) and does not take measures to control the quality and safety of this product, despite its rapid spread throughout the country. Аim of the Work is to summarize the results of scientific research on the toxicity of alternative opioids contained in Mitragyna speciosa and combined products based on them. Material and methods. Reports from the World Health Organization (WHO), the European Monitoring Center for Drugs and Drug Addiction (EMCDDA), the United Nations Office on Drugs and Crime, the results of scientific reviews and individual studies on biochemistry, toxicology, forensic identification of substances contained in products made from Mitragyna speciosa, over the past 10 years (Elsevier, PubMed, ToxNet). Results and Discussion. Recently, kratom has been cultivated on different continents and entered the market under the name "Kратом", in English-language sources - "Kratom". Kratom leaves are dried and sold in the form of green powder, tablets, capsules, extracts and gummies. In Ukraine, kratom is sold under hundreds of commercial names on the Internet as "Kratom", "Kratom product", "Kratom organic tea", "Kratom ethnic tea", "Kratom tea" and others. More than 40 structurally related alkaloids, as well as several flavonoids, terpenoid saponins, polyphenols and various glycosides were found in kratom leaves. The pharmacological and toxic effects of kratom for most of its components have not been studied enough. Like other dietary supplements, kratom products should be standardized for alkaloids, microbial contamination, pesticides, heavy metals, residual solvents, benzo(a)pyrene, aflatoxins, etc., with appropriate labeling requirements. Conclusions. Quality products should enter the Ukrainian market - standardized leaf extract of kratom, or other safe products made on its basis. However, recent studies show that mitraginine contained in kratom has great potential for medical science as a model for developing new approaches in very relevant areas of medicine: to treat pain and get rid of opioid dependence. Key Words: Mitragyna speciosa, alternative opioids, toxicity.
... Hassan, Pike, See, Sreenlivasan et al. (2020) compared the efficacy of MG to methadone for treating morphine withdrawal in rats concluding that MG treatment attenuated withdrawal symptoms significantly, similar to methadone and buprenorphine, and potentially with less undesired effects (Hassan et al., 2020). (Prozialeck et al., 2019), Yue et al., 2018;Coe et al., 2019;Hemby et al., 2019;Garcia-Romeu et al., 2020) No evidence of reward MG pretreatment reduced morphine self-administration Intracranial Self-Stimulation (ICSS) (Negus andMiller, 2014)-(Behnood-Rod et al., 2020) No evidence of reward for MG or 7-OH-MG Drug Discrimination Reeve et al., 2020;Obeng et al., 2021) MG showed partial generalization to multiple drugs, including morphine Strongest generalization of MG was to unscheduled drugs: phenylephrine and lofexidine 7-OH-MG showed full generalization to morphine Conditioned Place Preference (CPP) (Yusoff et al., 2018;Vijeepallam et al., 2019;Wilson et al., 2020;Japarin et al., 2021) Mixed evidence of CPP Physical Dependence/ Withdrawal (Harun et al., 2020;Hassan et al., 2020;Johari et al., 2021;Hassan et al., 20211778;Harun et al., 2021a) Mixed evidence of weak withdrawal across studies relative to morphine MG reduces morphine withdrawal and differs from morphine withdrawal on some measures Survey Data (Prozialeck et al., 2019), Coe et al., 2019;Garcia-Romeu et al., 2020), (Singh et al., 2014;Galbis-Reig, 2016;Swogger and Walsh, 2018;Smith et al., 2019;Harun et al., 2021b) Majority use is for health benefits, not recreational use or to get high. Use is almost exclusively oral, without the tendency of many recreational substance to smoke, inject, and/or nasally insufflate ...
... Recent studies confirm that kratom intake can lead to dependence and withdrawal in some kratom users, but these are substantially less likely to interfere with family, social and occupational life and commitments as compared to opioid dependence. Moreover, kratom is widely viewed as a healthier and less life-impairing substance to replace drugs such as opioids, alcohol, and stimulants (Singh et al., 2014;Galbis-Reig, 2016;Swogger and Walsh, 2018;Prozialeck et al., 2019). ...
... Although neither kratom nor any of its alkaloids are approved for therapeutic use for any disorder, surveys discussed in Factors 4, 5, and 6-History and Current Patterns of Abuse; the Scope, Significance and Duration of Abuse; what, if Any, Risk is There to the Public Health and elsewhere (Henningfield et al., 2018a;Grundmann et al., 2018;Swogger and Walsh, 2018;Coe et al., 2019;Prozialeck et al., 2019;Garcia-Romeu et al., 2020) show individuals in the US and around the world describe using kratom for its health benefits. Research characterizing kratom's effects, mechanisms of action, and therapeutic kratom alkaloid use rapidly advanced since 2018. ...
Drugs are regulated in the United States (US) by the Controlled Substances Act (CSA) if assessment of their abuse potential, including public health risks, show such control is warranted. An evaluation via the 8 factors of the CSA provides the comprehensive assessment required for permanent listing of new chemical entities and previously uncontrolled substances. Such an assessment was published for two kratom alkaloids in 2018 that the Food and Drug Administration (FDA) have identified as candidates for CSA listing: mitragynine (MG) and 7-hydroxymitragynine (7-OH-MG) (Henningfield et al., 2018a). That assessment concluded the abuse potential of MG was within the range of many other uncontrolled substances, that there was not evidence of an imminent risk to public health, and that a Schedule I listing (the only option for substances that are not FDA approved for therapeutic use such as kratom) carried public health risks including drug overdoses by people using kratom to abstain from opioids. The purpose of this review is to provide an updated abuse potential assessment reviewing greater than 100 studies published since January 1, 2018. These include studies of abuse potential and physical dependence/withdrawal in animals; in-vitro receptor binding; assessments of potential efficacy treating pain and substance use disorders; pharmacokinetic/pharmacodynamic studies with safety-related findings; clinical studies of long-term users with various physiological endpoints; and surveys of patterns and reasons for use and associated effects including dependence and withdrawal. Findings from these studies suggest that public health is better served by assuring continued access to kratom products by consumers and researchers. Currently, Kratom alkaloids and derivatives are in development as safer and/or more effective medicines for treating pain, substances use disorders, and mood disorders. Placing kratom in the CSA via scheduling would criminalize consumers and possession, seriously impede research, and can be predicted to have serious adverse public health consequences, including potentially thousands of drug overdose deaths. Therefore, CSA listing is not recommended. Regulation to minimize risks of contaminated, adulterated, and inappropriately marketed products is recommended.
... [6][7][8]10 In the wake of the intensifying opioid misuse crisis in U.S, kratom advocates believe kratom has the potential to be utilized as a harm reduction component among substance users who want to quit opioids. 9 Since it is increasingly used to self-manage substance use disorder (SUD), 10 further studies have also been conducted to characterize kratom's pharmacological properties, [11][12][13] and its side-effects. 14,15 Of the dozens of alkaloids, mitragynine is the most abundant alkaloid, and its metabolite 7-hydroxymitragynine, is reported to have unique opioid and non-opioid like-effects since it binds to opioid and adrenergic receptors. ...
... 23 Similarly, findings from field studies also show regular kratom consumption was not associated with significant alterations in the hematology and biochemical parameters. 4,21 Given that kratom is now widely touted as a safe herbal drug, 9 its unapproved utility has unfortunately contributed to kratom poisoning setbacks such as agitation, tachycardia, drowsiness, vomiting and confusion 14,20 and has irked clinicians and law enforcement agencies due to its health scare akin to opioids. 9 Apparently, it appeared that kratom users in the West are more prone to experience adverse health problems with kratom consumption than its allies in Southeast Asia (Davidson et al. 2021). ...
... 4,21 Given that kratom is now widely touted as a safe herbal drug, 9 its unapproved utility has unfortunately contributed to kratom poisoning setbacks such as agitation, tachycardia, drowsiness, vomiting and confusion 14,20 and has irked clinicians and law enforcement agencies due to its health scare akin to opioids. 9 Apparently, it appeared that kratom users in the West are more prone to experience adverse health problems with kratom consumption than its allies in Southeast Asia (Davidson et al. 2021). Although, the causation behind the clinical manifestation remains scarcely elucidated, more and more studies continue to highlight kratom's unique therapeutic usage. ...
Mitragyna speciosa (Korth.) also known as kratom or ketum has been traditionally used for its diverse medicinal value in Southeast Asia. Despite of its therapeutic value, kratom’s safety profile remains deficiently elucidated. Our study aims to characterize the urinary protein profile of regular kratom users to determine its toxic effects on renal functioning. A total of 171 respondents (comprising of n = 88 regular kratom users, and n = 83 healthy controls) were recruited for this study. Urine specimens were collected and analyzed using SDS-PAGE, followed by LC/MS/MS analysis. Our results show albumin is the primary, and most abundant form of protein excreted in kratom user’s urine specimens (n = 60/64), indicating that kratom users are predisposed to proteinuria. Kratom users had an elevated urinary protein (with an intensity of 66.7 kDa band), and protein: creatinine ratio (PCR) concentrations relative to healthy controls. However, kratom user’s urinary creatinine concentration was found to be in the normal range as the healthy control group. While, kratom users who tested positive for illicit drug use had an elevated urinary albumin concentration. Our preliminary findings indicate that regular consumption of freshly brewed kratom solution over a protracted period (for an average of eleven years) seems to induce proteinuria, suggestive of an early stage of kidney injury. Hence, further studies are urgently needed to confirm our findings, and establish kratom’s renal impairing effects.
... Although this includes social and recreational use, widely endorsed motivations involve self-treatment of symptoms associated with chronic pain, psychological disorders, and substance-use disorders (SUDs), including iatrogenic opioid dependence (Bath et al., 2020;Coe et al., 2019;Grundmann, 2017;Smith & Lawson, 2017;Smith, Rogers, Schriefer, et al., 2021;Swogger et al., 2015). For some, this reflects using kratom as a means for mitigating symptoms of withdrawal from opioids, as a short-or long-acting substitute for prescription and illicit opioids, as a self-treatment for opioid-use disorder (OUD), and possibly as a self-treatment for alcohol-use disorder (AUD) or stimulant-use disorders (Assanangkornchai et al., 2007;Boyer et al., 2008;Coe et al., 2019;Garcia-Romeu et al., 2020;Gutridge et al., 2020;Saref et al., 2019;Singh et al., 2021;Smid et al., 2018;Smith & Lawson, 2017;Smith, Rogers, Strickland, et al., 2021;Swogger et al., 2015;Swogger & Walsh, 2018;Tanguay, 2011;Vicknasingam et al., 2010). ...
... In U.S. surveys, people have routinely reported multiple motivations for use (Bath et al., 2020;Coe et al., 2019;Grundmann et al., 2017;Smith, Rogers, Schriefer, et al., 2021;Swogger & Walsh, 2018). Important within-group heterogeneity is reflected by the fact that some, but not all, people who use kratom also report prior or contemporaneous use of illicit psychoactive substances (Bath et al., 2020;Covvey et al., 2020;Garcia-Romeu et al., 2020;Smith & Lawson, 2017;Smith, Rogers, Schriefer, et al., 2021). ...
... Higher rates of lifetime incarceration (spending ≥1 night in jail) among respondents who used kratom may also be explained by the higher rates of illicit polydrug use among the kratom-use group and the fact that such use is often associated with criminal justice system involvement Smith & Lawson, 2017). It is also unsurprising that psychiatric health, QOL, and chronic pain were worse among people who reported lifetime kratom use, given that these are established motivations for initiating kratom use, rather than resulting from it (Bath et al., 2020;Coe et al., 2019;Garcia-Romeu et al., 2020;Grundmann, 2017;Singh et al., 2015;Swogger & Walsh, 2018). What is surprising is that these were ultimately not strong predictors of lifetime kratom use. ...
Kratom, a plant that produces opioid-like effects, has gained popularity in the U.S. for self-treating symptoms of chronic pain, mood disorders, and substance-use disorders (SUDs). Most data on kratom are from surveys into which current kratom-using adults could self-select; such surveys may underrepresent people who have used kratom and chosen to stop. Available data also do not adequately assess important psychosocial factors surrounding kratom use. In this study, U.S. adults who reported past 6-month alcohol, opioid, and/or stimulant use (N = 1,670) were recruited via Amazon Mechanical Turk between September and December 2020. Of the 1,510 evaluable respondents, 202 (13.4%) reported lifetime kratom use. Kratom-using adults, relative to others, were typically younger, male, unpartnered, without children, and had lower income. They had higher rates of chronic pain (31.7% vs. 21.9%, p = .003), childhood adversity, anxiety, and depression (p < .001), and lower perceived social rank (d = .19, .02-.22) and socioeconomic status (d = .37 .16-.26). They also reported higher use rates for most substances (except alcohol); this included medically supervised and unsupervised use of prescription opioids and diverted opioid agonist therapy (OAT) medications. Most (83.2%) met diagnostic criteria for any past-year SUD. Those reporting kratom use were less likely to reside in an urban/suburban area. The strongest predictors of kratom use were use of other drugs: cannabidiol (OR = 3.73), psychedelics (OR = 3.39), and nonmedical prescription opioids (OR = 1.72). Another strong predictor was lifetime OAT utilization (OR = 2.31). Despite seemingly poorer psychosocial functioning and health among respondents reporting lifetime kratom use, use of other substances may be the strongest indicators of kratom use. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
... Being an opioid-like herbal supplement, kratom is currently receiving global attention (Swogger and Walsh 2018;Prozialeck et al. 2019). Mitragyna Speciosa (Korth, Rubiaceae) or kratom is a native medicinal plant of Southeast Asia which has been used since ancient times for its vast medicinal properties by the local inhabitants in Malaysia and Thailand (Adkins et al. 2011;Hassan et al. 2013). ...
... Mitragyna Speciosa (Korth, Rubiaceae) or kratom is a native medicinal plant of Southeast Asia which has been used since ancient times for its vast medicinal properties by the local inhabitants in Malaysia and Thailand (Adkins et al. 2011;Hassan et al. 2013). Its popularity has grown extensively and is now widely used in the USA for its opioid-like pain-relieving effects and for management of opioid dependence and psychological problems (Grundmann 2017;Kruegel and Grundmann 2018;Swogger and Walsh 2018;Prozialeck et al. 2019;Eastlack et al. 2020). In contrast to natives that commonly consume kratom by either brewing the leaves into tea or chewing them fresh (Hassan et al. 2013), in the West, kratom can be readily purchased online and in street shops that comes in the form of powder, pills, capsules or concentrated extracts (Prozialeck et al. 2012). ...
... In contrast to natives that commonly consume kratom by either brewing the leaves into tea or chewing them fresh (Hassan et al. 2013), in the West, kratom can be readily purchased online and in street shops that comes in the form of powder, pills, capsules or concentrated extracts (Prozialeck et al. 2012). Thus, kratom as a new herbal alternative is gaining prominence and being widely used by those who are dependent on prescription and illicit opioid use (Singh et al. 2014;Grundmann 2017;Swogger and Walsh 2018;Coe et al. 2019). ...
RationaleKratom (Mitragyna speciosa Korth), a native medicinal plant of Southeast Asia, is proposed to exhibit potential therapeutic value as an opioid substitute. However, studies of its negative emotional states resulting from withdrawal particularly of its main psychoactive compound, mitragynine (MG), are limited.Objectives
Using the pentylenetetrazol (PTZ) discrimination assay, this study aims to investigate the effects of MG in responding to the PTZ stimulus and to assess the generalisation effects of withdrawal from MG to the PTZ stimulus.Methods
Rats (n = 20) were trained on a tandem (FR-10, VI-15) schedule of food reinforcement to press one lever after administration of the anxiogenic compound PTZ (16 mg/kg, i.p.) and an alternate lever after vehicle. Following acute tests, training was suspended, and rats were chronically treated with MG or morphine at 8-h intervals for 9 days and withdrawal was precipitated on the tenth day using naloxone (1 mg/kg, i.p.). The rats were tested for generalisation to PTZ at 2, 8 and 24 h after the last dose of MG or morphine administration.ResultsUnlike morphine that produced dose-related PTZ-like stimulus, MG at 3, 10, 30 and 45 mg/kg doses showed no substitution to the PTZ discriminative stimulus. In contrast to morphine which produced a time-dependent generalisation to the PTZ stimulus, naloxone did not precipitate withdrawal effects in MG-treated rats as they selected the vehicle lever at three withdrawal time points.Conclusion
These results demonstrate that MG produces a very different response to morphine withdrawal that is not associated with anxiogenic-like subjective symptoms. These characteristics of MG may provide further support for use as a novel pharmacotherapeutic intervention for managing opioid use disorder.
... 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. ...
... 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. ...
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. ...
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. ...
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.
... Mitragyna speciosa (Korth), often known as kratom, is a native medicinal plant of Southeast Asia that belongs to the Rubiaceae family [14,15]. This plant has been receiving global attention for its opioid-like pain-relieving effects and management of opioid dependence and psychological problems [16][17][18][19]. Although it is considered safe due to its natural origins [20], its potential risks to humans have been demonstrated in preclinical studies and clinical reports reporting evidence of toxicity, adverse effects, as well as abuse-and addictive-related effects. ...
... The difference in the method of administration would generate different rates of onset of drug effect, time span of effect, drug levels, absorption and metabolism [100,101]. Finally, differences in human reports and preclinical data may also be due to various cultural and demographic moderators of kratom use patterns and circumstances [18]. Hence, some of the findings may be inconsistent because the majority of the reports and claims are self-reporting studies that utilized estimated kratom juice or extract with no conduct of clinical evaluation to assess the severity of the claimed kratom-related effects. ...
Opioid use disorder (OUD) has become a significant public health issue worldwide. Methadone and buprenorphine are the most common medications used for treating OUD. These drugs have the potential to assist many patients in managing their opioid dependence and withdrawal but they are currently misused and associated with certain compliance issues, side effects, and risk of relapse. As an opioid-like herbal supplement, Mitragyna speciosa Korth or kratom has received increased attention for managing chronic pain and opioid withdrawal symptoms. Nevertheless, the use of kratom as a self-treatment medication for opioid dependence continues to be controversial due to concerns raised about its effectiveness, safety, and abuse liability. The main active alkaloid constituent of the plant, mitragynine, has been shown to act as a partial mu-opioid agonist. Given this pharmacology, studies have been focusing on this psychoactive compound to examine its potential therapeutic values as medication-assisted therapy (MAT). This review aims to provide a current preclinical overview of mitragynine as a prospective novel option for MAT and summarise the recent developments in determining if the plant’s active alkaloid could provide an alternative to opioids in the treatment of OUD.
... Überdies wird eine Inhibition verschiedener UDP-Glucuronosyltransferasen angenommen, darunter auch UGT2B7, deren Substrate z. B. Buprenorphin, Ketamin, aber auch Morphin und Hydromorphon sind [8,26] [27]. Allerdings soll sich die Symptomatik im Vergleich zu einem Opiatentzug in einer milderen Form präsentieren [27]. ...
... B. Buprenorphin, Ketamin, aber auch Morphin und Hydromorphon sind [8,26] [27]. Allerdings soll sich die Symptomatik im Vergleich zu einem Opiatentzug in einer milderen Form präsentieren [27]. ...
Background
Consumption of the psychotropic plant kratom (botanical name: Mitragyna speciosa) is sometimes used for the self-medication of chronic or acute pain. An increase in the use is possible in Germany in the future.Objective
This review provides an overview on kratom for pain specialists. The topics of the review are the pharmacological aspects, the mental effects, the effects on pain and the risks of kratom including possible addiction.Material and methodsWe conducted a review of literature in PubMed published until 15 January 2021 resulting in 426 publications of which 8 were specifically concerned with the topic of kratom and pain.ResultsIn addition to other alkaloids, kratom also contains 7‑hydroxymitragynine, which is active on opioid receptors. The use of kratom is not without risks, e.g. because there is no standardized form of administration as well as the possibility of direct damage to health and of addiction.DiscussionThere are currently no evidence-based reasons to recommend the use of kratom as an analgesic. It is important for pain specialists to ask patients about a possible abuse of kratom and to be able to inform the patients about the potential risks of kratom.
... Kratom (Mitragyna speciosa) is a tree that is native to Southeast Asia and although the complex composition and psychopharmacology is not fully understood, it is known to bind as a partial agonist to kappa (j), delta (d) and predominantly mu (l) opioid receptors (Adkins et al., 2011;Bath et al., 2020;Bowe and Kerr, 2020). In recent years, it has gained popularity in the Western world as a herbal supplement, typically taken by brewing powdered leaves to make a drink that may be taken for a variety of conditions, including anxiety, depression, inflammation, pain and opioid dependency (Bath et al., 2020;Coe et al., 2019;Eastlack et al., 2020;Prozialeck et al., 2020;Swogger and Walsh, 2018). ...
... Side effects can be wide ranging and more severe at greater doses and as a result of prolonged use: seizures, liver injury, cardiac abnormalities, accidental overdoses and associated fatalities have been known to occur (Abdullah et al., 2019a;Afzal et al., 2020;Aggarwal et al., 2018;Boyer et al., 2008;Matson and Schenk, 2019;Schimmel and Dart, 2020). Kratom has also been associated with dependency, cravings, tolerance and deterioration in physical well-being; though the severity of kratom withdrawal symptoms can vary greatly for different individuals (Abdullah, 2020;Abdullah et al., 2019b;Khazaeli et al., 2018;Singh et al., 2014;Swogger and Walsh, 2018). Dependence may be more likely if used in excessively high doses for the self-management of opioid withdrawal (Bath et al., 2020;Galbis-Reig, 2016). ...
We describe a case report where buprenorphine was successfully used for the management of kratom (Mitragyna speciosa) dependency during the Covid-19 pandemic in a specialist community substance misuse treatment service. The individual had a notable iatrogenic dependency on oral over the counter and prescribed opioid medication. She resorted to using kratom as a ‘tea’ to self-detoxify before getting into difficulty. Upon presentation, she disclosed using kratom up to 70 g/day with hourly dosing, in addition to co-codamol (8 mg codeine/500 mg paracetamol tablets) three times a week. Initiation of oral buprenorphine sublingual tablets was complicated due to Covid-19: dispensing arrangements were liberalised from the outset and the dose was incrementally increased, eventually to 24 mg/day. Comorbidities included mental health conditions and chronic pain which improved with buprenorphine treatment and psychotherapy. Further research is required to determine optimal regimens for the management of kratom dependency. This case study adds to the current paucity of published data regarding how to manage such cases in the community setting, which is important since kratom is thought to be increasingly used in the western world.
... Dependence in kratom is well documented in human (Suwanlert, 1975;Vicknasingam et al., 2010;Ahmad and Aziz, 2012;Singh et al., 2014). Nevertheless, although kratom has been reported to cause dependence and withdrawal signs, these symptoms are usually milder than after opiate withdrawal (Prozialeck, 2016;Saingam et al., 2016;Grundmann, 2017;Singh et al., 2018b;Swogger and Walsh, 2018). Singh et al. (2018b) reported that kratom depended patients did not seek for medication as kratom withdrawal symptoms were mostly rather mild and only lasted between one to three days. ...
... However, aggressive kratom consumption pattern may cause escalation of consumption and more severe withdrawal signs . Indeed, withdrawal periods are highly aversive, which makes it hard for an individual to maintain abstinence (Swogger and Walsh, 2018). At the moment, there is no particular treatment for kratom dependence and withdrawal symptoms. ...
Background: Kratom or Mitragyna speciosa Korth has been widely used to relieve the severity of opioid withdrawal in natural settings. However, several studies have reported that kratom may by itself cause dependence following chronic consumption. Yet, there is currently no formal treatment for kratom dependence. Mitragynine, is the major psychoactive alkaloid in kratom. Chronic mitragynine treatment can cause addiction-like symptoms in rodent models including withdrawal behaviour. In this study we assessed whether the prescription drugs, methadone, buprenorphine and clonidine, could mitigate mitragynine withdrawal effects. In order to assess treatment safety, we also evaluated hematological, biochemical and histopathological treatment effects.
Methods: We induced mitragynine withdrawal behaviour in a chronic treatment paradigm in rats. Methadone (1.0 mg/kg), buprenorphine (0.8 mg/kg) and clonidine (0.1 mg/kg) were i.p. administered over four days during mitragynine withdrawal. These treatments were stopped and withdrawal sign assessment continued. Thereafter, toxicological profiles of the treatments were evaluated in the blood and in organs.
Results: Chronic mitragynine treatment caused significant withdrawal behaviour lasting at least 5 days. Methadone, buprenorphine, as well as clonidine treatments significantly attenuated these withdrawal signs. No major effects on blood or organ toxicity were observed.
Conclusion: These data suggest that the already available prescription medications methadone, buprenorphine, and clonidine are capable to alleviate mitragynine withdrawal signs rats. This may suggest them as treatment options also for problematic mitragynine/kratom use in humans.
... 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]. ...
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. ...
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. ...
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]. ...
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]. ...
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.
... Mitragyna speciosa (i.e., kratom) has emerged as an alternative to traditional medical treatments for opioid and alcohol dependence (Kruegel & Grundmann, 2018). In its native region of Southeast (SE) Asia, kratom is traditionally consumed orally by chewing raw kratom leaves or boiling leaves into a tea, which opposes the encapsulated powder form more typically consumed in the United States (Swogger & Walsh, 2018). Kratom contains over 20 biologically active alkaloid constituents, with mitragynine (MG) being the most prevalent (Jansen & Prast, 1988;Raffa et al., 2013). ...
Background and Purpose: Mitragynine (MG) is an alkaloid found in Mitragyna speciosa (kratom) that is used as an herbal remedy for pain relief and opioid withdrawal. MG acts at μ-opioid and α-adrenergic receptors in vitro, but the physiological relevance of this activity in the context of neuropathic pain remains unknown. The purpose of the present study was to characterize the effects of MG in a mouse model of CIPN, and to investigate the potential impact of sex on MG’s therapeutic efficacy. Experimental Approach: Inhibition of oxaliplatin-induced mechanical hypersensitivity was measured following intraperitoneal administration of MG. Both male and female C57BL/6J mice were used to characterize potential sex-differences in MG’s therapeutic efficacy. Pharmacological mechanisms of MG were characterized through pretreatment with the opioid and adrenergic antagonists naltrexone, prazosin, yohimbine, and propranolol (1, 2.5, 5 mg/kg). Key Results: Oxaliplatin produced significant mechanical allodynia of equal magnitude in both male and females, which was dose-dependently attenuated by repeated MG exposure. MG was more potent in males vs females, and the highest dose of MG (10 mg/kg) exhibited greater anti-allodynic efficacy in males. Mechanistically, activity at µ-opioid, α1- and α2-adrenergic receptors, but not β-adrenergic receptors contributed to the effects of MG against oxaliplatin-induced mechanical hypersensitivity. Conclusions and Implications: Repeated MG exposure significantly attenuated oxaliplatin-induced mechanical hypersensitivity with greater potency and efficacy in males, which has crucial implications in the context of individualized pain management. The opioid and adrenergic components of MG indicate that it shares pharmacological properties with clinical neuropathic pain treatments.
... Activation of β-arrestin-2 is associated with the adverse effects of opioid receptor activation i.e., respiratory depression, constipation, and addiction [8,9]. Regarding the consumption of kratom, several withdrawal symptoms have been reported, such as muscle and bone pain, insomnia, anxiety, decreased appetite, and severe craving [10,11]. ...
Mitragynine (MTR), the main indole alkaloid of the well-known plant kratom (Mitragyna speciosa), is one of the most studied natural products nowadays, due to its remarkable biological effects. It is a partial agonist on the opioid receptors, and as such relieves pain without the well-known side-effects of the opioids applied in the clinical practice. MTR and its derivatives therefore became novel candidates for drug development. The poor aqueous solubility and low bioavailability of drugs are often improved by cyclodextrins (CyDs) as excipients through host-guest type complex formation. Among the wide variety of CyDs, sulfobutylether-beta-cyclodextrin (SBEβCyD) is frequently used and official in the European and U.S. Pharmacopoeia. Herein, the host-guest complexation of MTR with βCyD and SBEβCyD was studied using chiroptical and NMR spectroscopy. It was found by NMR measurements that MTR forms a rather weak (logβ11 = 0.8) 1:1 host-guest complex with βCyD, while the co-existence of the 2MTR∙SBEβCyD and MTR∙SBEβCyD species was deducted from 1H NMR titrations in the millimolar MTR concentration range. Sulfobutylation of βCyD significantly enhanced the affinity towards MTR. The structure of the formed inclusion complex was extensively studied by circular dichroism spectroscopy and 2D ROESY NMR. The insertion of the indole moiety was confirmed by both techniques.
... Nevertheless, these larger surveys have been able to elucidate many broad motivations for why persons may be using kratom, such as the self-treatment for chronic pain, fatigue, psychiatric, or SUD symptoms or to improve energy, mood, and enhance recreation generally (Grundmann, 2017;Swogger and Walsh, 2018;Coe et al., 2019;Bath et al., 2020;Garcia-Romeu et al., 2020). These reports corroborate findings from Southeast Asia (Singh et al., 2016;Singh et al., 2017;Singh et al., 2019a;Singh et al., 2020b;Müller et al., 2020). ...
There is limited understanding regarding kratom use among US adults. Although motivations for use are increasingly understood, typical kratom doses, threshold of (low and high) doses for perceived effectiveness, and effects produced during cessation are not well documented. We aimed to extend prior survey work by recruiting adults with current and past kratom exposure. Our goal was to better understand kratom dosing, changes in routines, and perception of effects, including time to onset, duration, and variability of beneficial and adverse outcomes from use and cessation. Among respondents who reported experiencing acute kratom effects, we also sought to determine if effects were perceived as helpful or unhelpful in meeting daily obligations. Finally, we attempted to detect any signal of a relationship between the amount of kratom consumed weekly and weeks of regular use with ratings of beneficial effects from use and ratings of adverse effects from cessation. We conducted an online survey between April-May 2021 by re-recruiting participants from a separate study who reported lifetime kratom use. A total of 129 evaluable surveys were collected. Most (59.7%) had used kratom >100 times and reported currently or having previously used kratom >4 times per week (62 weeks on average). Under half (41.9%) reported that they considered themselves to be a current “regular kratom user.” A majority (79.8%) reported experiencing acute effects from their typical kratom dose and that onset of effects began in minutes but dissipated within hours. Over a quarter reported that they had increased their kratom dose since use initiation, whereas 18.6% had decreased. Greater severity of unwanted effects from ≥1 day of kratom cessation was predicted by more weeks of regular kratom use ( β = 6.74, p = 0.02). Acute kratom effects were largely reported as compatible with, and sometimes helpful in, meeting daily obligations. In the absence of human laboratory studies, survey methods must be refined to more precisely assess dose-effect relationships. These can help inform the development of controlled observational and experimental studies needed to advance the public health understanding of kratom product use.
... Currently, a variety of kratom products (loose leaf, powder, capsules, concentrate) can be legally purchased from online retailers, smoke shops, convenience stores, and specialty supplement shops in 46 US states (Griffin et al., 2016;Fowble and Musah, 2019). Exploratory surveys in the US seeking to better understand kratom use, motivations, and effects have found that many people report using kratom to "self-manage" chronic pain, fatigue, psychiatric, and symptoms of substance use disorders (SUDs), including opioid-withdrawal symptom relief and/or as a replacement for full opioid agonists (Bath et al., 2020;Boyer et al., 2008;Coe, et al., 2019;Garcia-Romeu, et al., 2020;Grundmann, 2017;Smith and Lawson, 2017;Swogger and Walsh, 2018). ...
Kratom products available in the United States are becoming increasingly diverse both in terms of content and in terms of how they are marketed. Prior survey research indicates that kratom has been primarily used in the US to self-treat anxiety, depression, pain, fatigue, and substance use disorder (SUD) symptoms. Kratom is also well-known for its use as a short- or long-term full opioid agonist substitute. Therefore, use may be greater in regions particularly impacted by addiction to prescription opioids. Use may also be greater in demographic groups targeted by media outlets (such as specific podcasts) in which kratom is touted. Here, we aimed to determine whether lifetime and past-year kratom use were associated with region of residence and with being young, White, post-secondary educated, and employed. To strengthen confidence in our findings, we analyzed data from two sources: our own crowdsourced online convenience sample and the 2019 National Survey on Drug Use and Health (NSDUH). In our sample (N = 2,615), 11.1% reported lifetime and 6.7% reported past-year kratom use, and the odds of kratom use were higher among people who were White, younger, at least high school educated, employed, and above the poverty line, as well as those reporting nonmedical opioid use, past-year SUD, or lifetime SUD treatment; residence was not a significant predictor. In NSDUH data, suburban residence and other demographic factors, concordant with those from the crowdsourced sample, were associated with kratom use. Taken together, the findings support a general “White middle-class suburban” profile of the modal kratom user, but more research is needed to understand it. In the interim, focus should be on our finding that lifetime nonmedical opioid use was associated with an up to five times greater likelihood of past-year kratom use, suggesting that drug-use history may presently be the strongest predictor of kratom use.
... M. speciosa is beneficial in the treatment of opioid withdrawal. However, this species can induce addiction and cause withdrawal symptoms such as muscle spasms and pain, difficulty sleeping, watery eyes/nose, hot flashes, fever, and decreased appetite [12,13]. Many reports show that Kratom overdose causes death [14][15][16]. ...
Plants in the genus Mitragyna (Rubiaceae) are used in traditional medicine because of their broad therapeutic activity. Four Mitragyna species, M. speciosa (Roxb.) Korth. (MS), M. rotundifolia (Roxb.) Kuntze (MR), M. diversifolia (Wall. ex G. Don) Havil. (MD), and M. hirsuta Havil. (MH), occur in Thailand. M. speciosa, commonly known as ‘Kratom’ in Thai, is the only narcotic species for which buying, selling, importing or possessing has been prohibited by law in Thailand and some other countries. Mitragynine and 7-hydroxymitragynine, the major psychoactive compounds, are important in the treatment of opioid withdrawal. However, this species is used in traditional medicine to relieve pain and inflammation. Consequently, a rapid and easy technique for differentiating M. speciosa from closely related species is needed for routine forensic analysis. In this study, polymerase chain reaction coupled with lateral flow immunochromatographic assay (PCR-LFA) based on matK was developed for the detection of M. speciosa in forensic specimens. Duplex primers (MS-F-FAM, Ctrl-F-DIG and Ctrl-R-Biotin) were designed based on species-specific nucleotide indels observed exclusively in the matK sequences of M. speciosa. Positive results for M. speciosa are indicated by the clear presence of three black lines on the lateral flow cassette. Forensic samples were investigated, and the three black test lines indicating M. speciosa were observed for seven of eight specimens. PCR-LFA has been proven to be fast, easy and efficient for detecting the narcotic M. speciosa and could be developed as a rapid forensic diagnostic technique for other plants.
... Even though kratom has been used in Southeast Asia for generations, it is only over the past 10-20 years that kratom use has expanded to Europe and North America (Prozialeck et al., 2012;Grundmann, 2017). In the United States, kratom products are used extensively for the self-management of pain, opioid use disorder and depression (Swogger et al., 2015;Grundmann, 2017;Swogger and Walsh, 2018;Schimmel et al., 2021). It has been estimated that there may be as many as 1-3 million kratom users in the United States (Prozialeck et al., 2019;Palamar, 2021;Schimmel et al., 2021). ...
Kratom (Mitragyna speciosa, Korth.) is an evergreen tree that is indigenous to Southeast Asia. When ingested, kratom leaves or decoctions from the leaves have been reported to produce complex stimulant and opioid-like effects. For generations, native populations in Southeast Asia have used kratom products to stave off fatigue, improve mood, alleviate pain and manage symptoms of opioid withdrawal. Despite the long history of kratom use in Asia, it is only within the past 10–20 years that kratom has emerged as an important herbal agent in the United States, where it is being used for the self-treatment of pain, opioid withdrawal symptoms, and mood disorders. The increase in the use of kratom in the United States has coincided with the serious epidemic of opioid abuse and dependence. Since 2015, efforts to restrict access to prescription opioids have resulted in a marked increase in the use of “street” opioids such as heroin and illicit fentanyl. At the same time, many patients with chronic pain conditions or opioid use disorder have been denied access to appropriate medical help. The lack of access to care for patients with chronic pain and opioid use disorder has been magnified by the emergence of the COVID-19 pandemic. In this report, we highlight how these converging factors have led to a surge in interest in kratom as a potential harm reduction agent in the treatment of pain and opioid use disorder.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Zusammenfassung
Kratom ist ein immergrüner Baum, der in Südostasien heimisch ist und dessen Blätter traditionell als Stimulans, als Therapie bei verschiedenen gesundheitlichen Problemen und zu religiösen Zwecken verwendet werden. Insbesondere in den USA (geringer auch in Europa) wird seit einigen Jahren eine relevante Prävalenz des Kratomkonsums beobachtet. In westlichen Ländern wird Kratom überwiegend als Analgetikum und Stimulans, zur Behandlung von Schmerzen und Opioidgebrauchsstörungen und zur günstigen Beeinflussung der psychischen Gesundheit (z. B. bei Depression, Angststörungen) verwendet. Die chemischen Hauptbestandteile von Kratom sind Alkaloide, von denen Mitragynin und 7-Hydroxymitragynin am bedeutsamsten erscheinen. Die Pharmakodynamik und -kinetik von Kratom sind komplex und unzureichend untersucht. Bekannt ist, dass Mitragynin und 7-Hydroxymitragynin Partialagonisten an humanen μ-Opioidrezeptoren und Antagonisten an κ- und δ-Opioidrezeptoren bei zusätzlichen Effekten an weiteren zentralen Rezeptoren sind. Die Verträglichkeit von Kratom scheint im Vergleich mit klassischen Opioiden besser zu sein, was mit fehlenden Effekten von Kratom auf β-Arrestin in Verbindung gebracht und als Ausgangspunkt für die Entwicklung besser verträglicher Opioide diskutiert wurde. Einige Alkaloide in Kratom sind Inhibitoren von CYP2D6, geringer auch CYP2C19 und CYP3A4. Das Abhängigkeitspotential von Kratom scheint geringer ausgeprägt zu sein als das von klassischen Opioiden, wobei die Datenlage dazu begrenzt ist und Kratomgebrauchsstörungen primär in westlichen Längern auftreten. Es sind zahlreiche Fälle von schwerwiegenden gesundheitlichen Problemen und Todesfälle im Zusammenhang mit Kratomkonsum in den USA bekannt, wobei in diesen Fällen meist mehrere Substanzen involviert waren. Kratomkonsum ist vermutlich mit hepatotoxischen und kardiotoxischen Effekten assoziiert. Kratom-assoziierte Morbidität und Mortalität unterscheiden sich zwischen westlichen Ländern und Südostasien, wo Kratomkonsum kein öffentliches Gesundheitsproblem darstellt, quantitativ erheblich. Als Gründe hierfür wurden der in westlichen Ländern verbreitete Mischkonsum, höhere Dosierungen konsumierten Kratoms, Verfälschungen und Verunreinigungen kommerziell erhältlicher Kratomprodukte in westlichen Ländern, pharmakokinetische Interaktionen und höhere Konzentrationen von 7-Hydroxymitragynin in getrockneten Kratomblättern (die typischerweise in westlichen Ländern konsumiert werden) im Vergleich mit frischen Blättern (die typischerweise in Südostasien konsumiert werden) genannt.
Objective:
The increasingly widespread use of kratom in the United States has raised concerns about its safety as well as spurring research into potential applications of its active ingredients in medical treatments.
Methods:
We reviewed the literature published over the past 20 years, including peer-reviewed publications and data released by United States government health agencies to provide an overview of this topic.
Results:
A variety of potentially beneficial and adverse effects of kratom use related to its opioid and stimulant properties have been documented, including addiction and withdrawal. Preliminary research in animals and case reports in humans have suggested medical utility for kratom in treating alcohol and opioid use disorders, pain, depression, and anxiety. However, the lack of controlled, standardized studies limits the clinical utility of this agent and is a barrier to safe consumption.
Conclusions:
Historically, kratom has been used for medical purposes and for the treatment of alcohol and substance use disorders. The currently available literature suggests a potential for similar clinical applications. However, without controlled research studies or regulation, kratom poses numerous health risks to consumers.
Co-use of non-medical opioids (NMO) and methamphetamine is increasing. So too is the use of the psychoactive botanical “kratom,” including among people with NMO and methamphetamine use histories. We assessed characteristics associated with respondent groups who reported lifetime methamphetamine and/or kratom use within a nationally representative US sample using 2019 National Survey on Drug Use and Health data from respondents reporting lifetime NMO use (diverted prescription opioids, heroin). Weighted prevalence estimates for demographic, mental health, and substance use outcomes were determined. Logistic regression examined associations between group membership and outcomes. Among this sample of respondents with lifetime NMO use, 67.6% (95% CI = 65.6–69.4%) reported only NMO use; 4.6% (3.9–5.4%) reported NMO+Kratom; 24.7% (22.7–26.7%) reported NMO+Methamphetamine; and 3.2% (2.5–3.9%) reported NMO+Methamphetamine+Kratom. Compared to those in the NMO-only group, the NMO+Kratom group was more likely to report past-year serious mental illness (SMI; OR = 2.27), suicidality (OR = 1.89), and past-month psychological distress (OR = 1.88). The NMO+Methamphetamine+Kratom group was more likely to report past-year SMI (OR = 2.65), past-month psychological distress (OR = 2.06), and unmet mental health needs (OR = 2.03); increased odds for drug injection, opioid withdrawal, and perceived treatment need also emerged. Risk factors were observed for all groups but were greatest among those reporting use of all three substances.
Kratom (Mitragyna speciosa) consists of over 40 alkaloids with two of them, mitragynine (MG) and 7‐OH‐mitragynine (7‐OH‐MG) being the main psychoactive compounds. MG and 7‐OH‐MG each target opioid receptors and have been referred to as atypical opioids. They exert their pharmacologic effects on the μ, δ, and κ opioid receptors. In addition, they affect adrenergic, serotonergic, and dopaminergic pathways. Kratom has been touted as an inexpensive, legal alternative to standard opioid replacement therapy such as methadone and buprenorphine. Other uses for kratom include chronic pain, attaining a “legal high,” and numerous CNS disorders including anxiety depression and post‐traumatic stress disorder (PTSD). Kratom induces analgesia and mild euphoria with a lower risk of respiratory depression or adverse central nervous system effects compared to traditional opioid medications. Nonetheless, kratom has been associated with both physical and psychological dependence with some individuals experiencing classic opioid withdrawal symptoms upon abrupt cessation. Kratom use has been linked to serious adverse effects including liver toxicity, seizures, and death. These risks are often compounded by poly‐substance abuse. Further, kratom may potentiate the toxicity of coadministered medications through modulation of cytochrome P450, P‐glycoprotein, and uridine diphosphate glucuronosyltransferase enzymes (UGDT). In 2016 the U.S. Drug Enforcement Administration (DEA) took steps to classify kratom as a federal schedule 1 medication; however, due to public resistance, this plan was set aside. Until studies are conducted that define kratom's role in treating opioid withdrawal and/or other CNS conditions, kratom will likely remain available as a dietary supplement for the foreseeable future. This article is protected by copyright. All rights reserved
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.
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.
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.
Despite the potential importance of understanding excess mortality among people with mental disorders, no comprehensive meta-analyses have been conducted quantifying mortality across mental disorders.
To conduct a systematic review and meta-analysis of mortality among people with mental disorders and examine differences in mortality risks by type of death, diagnosis, and study characteristics.
We searched EMBASE, MEDLINE, PsychINFO, and Web of Science from inception through May 7, 2014, including references of eligible articles. Our search strategy included terms for mental disorders (eg, mental disorders, serious mental illness, and severe mental illness), specific diagnoses (eg, schizophrenia, depression, anxiety, and bipolar disorder), and mortality. We also used Google Scholar to identify articles that cited eligible articles.
English-language cohort studies that reported a mortality estimate of mental disorders compared with a general population or controls from the same study setting without mental illness were included. Two reviewers independently reviewed the titles, abstracts, and articles. Of 2481 studies identified, 203 articles met the eligibility criteria and represented 29 countries in 6 continents.
One reviewer conducted a full abstraction of all data, and 2 reviewers verified accuracy.
Mortality estimates (eg, standardized mortality ratios, relative risks, hazard ratios, odds ratios, and years of potential life lost) comparing people with mental disorders and the general population or people without mental disorders. We used random-effects meta-analysis models to pool mortality ratios for all, natural, and unnatural causes of death. We also examined years of potential life lost and estimated the population attributable risk of mortality due to mental disorders.
For all-cause mortality, the pooled relative risk of mortality among those with mental disorders (from 148 studies) was 2.22 (95% CI, 2.12-2.33). Of these, 135 studies revealed that mortality was significantly higher among people with mental disorders than among the comparison population. A total of 67.3% of deaths among people with mental disorders were due to natural causes, 17.5% to unnatural causes, and the remainder to other or unknown causes. The median years of potential life lost was 10 years (n = 24 studies). We estimate that 14.3% of deaths worldwide, or approximately 8 million deaths each year, are attributable to mental disorders.
These estimates suggest that mental disorders rank among the most substantial causes of death worldwide. Efforts to quantify and address the global burden of illness need to better consider the role of mental disorders in preventable mortality.
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.
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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.
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.
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.
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.
The consumption of Mitragyna speciosa (MS) for its psychoactive effects is widely reported amongst people in the villages in Thailand and Malaysia even though its use is illegal.
This study examined the pattern of MS use, its reported effects and explored its potential to cause dependence.
We used both convenience and snowball-sampling methods to recruit participants in a border town between two northern states in Malaysia. Face-to-face interviews were conducted with the use of a structured questionnaire on 562 respondents who gave oral consent to participate in the study.
The response rate was 91%. The majority of the respondents (88%) reported daily use of MS. The main mode of using MS was by drinking the MS extract as tea (90%). The mean age of starting MS use was 28.3 (SD=8.1) years. A variety of reasons were given for using MS including for social and recreational needs, stamina and physical endurance, pain relief and improved sexual performance. Despite its reported usefulness in weaning off opiate addiction, 460 (87%) admitted they were not able to stop using MS. Only education level had a statistically significant association with the ability to stop or not stop the use of MS (χ(2)=31.0, df=1, p<0.001). Significantly higher proportions of those with a lower education level (38%) were able to stop using MS compared to respondents with a higher education level.
Our study provides important information on the pattern of MS use, its effects and its potential to cause addiction, as there has been growing interest in MS as evidenced by the number of advertisements for its sale on the Internet. Future study is required to explore its psychological and social impact on users.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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."