Article
To read the full-text of this research, you can request a copy directly from the authors.

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.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... [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. ...
Article
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.
... 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). ...
Article
Full-text available
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.
... 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). ...
Article
Full-text available
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.
... Nevertheless, kratom's use as a harm reduction tool in individuals with opioid use disorder cannot be ignored. Although clinically approved opioids such as methadone and buprenorphine are prescribed for this purpose, users who self-medicate with kratom report improved mood and reduced anxiety (Swogger & Walsh, 2018). ...
... There are numerous studies detailing the positive and negative effects of kratom (McWhirter & Morris, 2010). Enhanced mood and reduced anxiety are among the perceived mental health benefits associated with the drugs' use (Swogger & Walsh, 2018). However, negative psychosocial effects resulting in tolerance, withdrawal symptoms, and difficulty with abstinence are also reported. ...
... It has been suggested that kratom extracts can help with ethanol withdrawal symptoms by reducing alcohol intake (Cheaha, Keawpradub, Sawangjaroen, Phukpattaranont, & Kumarnsit, 2015; Gutridge et al., 2020). Despite the known T A B L E 2 Adverse effects associated with kratom (Afzal, Esang, & Rahman, 2020;Hassan et al., 2013;Post et al., 2019;Prozialeck et al., 2012;Sabetghadam, Navaratnam, & Mansor, 2013;Saingam et al., 2013;Singh et al., 2014;Swogger & Walsh, 2018;Wong & Mun, 2020) Agitation Altered mental status Vomiting toxic effects of the drug, the toxidrome presented is highly dependent on dose, duration of use (tolerance), and potential drug-drug interactions. ...
Article
Kratom is a botanical substance derived from the leaves of Mitragyna speciosa. Although kratom has been used traditionally in Southeast Asia for over a century, recreational use and non‐medically supervised use of the drug in the West has escalated considerably over the past decade. Viewed as a legal, “safe” or “natural” alternative to opioids, kratom has gained widespread use for the non‐medically supervised treatment of chronic pain, anxiety, and opioid withdrawal. Kratom consists of a complex mixture of more than 50 alkaloids, of which mitragynine and 7‐hydroxymitragynine are the principal compounds of interest due to their abundance and heightened affinity for the mu opioid receptor, respectively. Mitragynine, which is structurally and pharmacologically distinct from traditional opioids, exhibits a multimodal mechanism of action which accounts for its complex adrenergic, serotonergic, and opioid‐like effects. Adverse effects including fatalities have been associated with kratom's use, often in combination with other drugs. While users report numerous benefits associated with its use, lack of regulatory control and escalating use among individuals with opioid use disorder has attracted widespread concern. In this review the origins, pharmacology, uses, effects, and analysis of the drug are reviewed from a toxicological standpoint. This article is categorized under: • Toxicology > New Psychoactive Substances • Toxicology > Opioids • Toxicology > Plants and Poisons Abstract Kratom: A systematic review of toxicological issues.
... 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. ...
Article
Full-text available
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.
... To date, there have been no rigorous clinical studies of kratom that would meet the FDA's standards for safety. Nonetheless, observational studies and surveys (see Grundmann 2017;Swogger and Walsh 2018) indicate that those who have used kratom experienced pain relief, enhanced mood and relief of opioid withdrawal symptoms. Mainly because of its unique painrelieving and perceived medicinal benefits, kratom is widely promoted on the internet and sold in retail outlets unique to tobacco and cannabis (e.g., head or smoke shop) in the US (Grundmann 2017) and elsewhere. ...
... Especially when used in combination with other substances (e.g., diphenhydramine, ethanol, benzodiazepines, opioids and stimulants), kratom has been said to contribute to serious medical outcomes such as seizures, respiratory depression, coma, increased bilirubin, bradycardia, rhabdomyolysis, renal failure, respiratory arrest, cardiac arrest and cyanosis (Post et al. 2019). While causation cannot be inferred from these case studies and poison control reports (Swogger and Walsh 2018), caution is warranted until more and better data on potential harms of kratom use are available. ...
... As a result, individuals may continue to regard kratom negatively without weighing its utility, particularly among those struggling with their illicit drug use problem. Since kratom is being used to self-treat opioid dependence, researchers have opined that kratom can be used as a harm-reduction tool (Swogger and Walsh 2018), particularly to treat pain and withdrawal among opioid users (Coe et al. 2019;Grundmann 2017). ...
Article
Kratom (Mitragyna speciosa), an indigenous medicinal plant of Southeast Asia, is believed to be harmful. We compared the perceptions toward kratom use among kratom users and non-users in Malaysia. 356 respondents (137 kratom users and 219 non-users) were recruited for this cross-sectional study. The majority of respondents were male (60%, n = 212/356), Malays (88%), and 51% were ≥37 years old. Non-users showed higher unadjusted odds of reporting a perception that kratom use can cause addiction (OR = 6.72, CI: 3.91–11.54, p < .0001), withdrawal symptoms (OR = 7.58, CI: 4.62–12.42, p < .0001), illicit drug use problems (OR = 10.12, CI: 6.14–16.68, p < .0001), impaired social-functioning (OR = 12.05, CI: 7.24–20.05, p < .0001), and health problems (OR = 10.44, CI: 6.32–17.24, p < .0001). Similarly, non-users viewed kratom policies differently from kratom users, displaying increased odds of reporting the belief that kratom use and sales must be regulated with stringent laws (OR = 5.75, CI: 3.61–9.18, p < .0001), and kratom should be regulated instead under the Dangerous Drugs Act 1952 to overcome kratom use problems (OR = 8.26, CI: 4.94–13.82, p < .0001). Because of the disconnect in kratom use perceptions and personal experiences between kratom users and non-users, hastily criminalizing kratom without investigating carefully its scientific merits can significantly impede future kratom research.
... 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. ...
Article
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).
... 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). ...
Article
Full-text available
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.
... Given the present opioid abuse epidemic in the US, the use of M. speciosa has become increasingly popular when a significant number of users have reported on its use as a tool to stop or reduce the use of prescription or illicit opioids. [9][10][11] Hence, the increased consumption and demand for M. speciosa have accelerated discussion of whether its potential therapeutic value may outweigh its safety risk and abuse potential. The concern is whether the users who try to self-treat opioid withdrawal may possess the risk of developing undesirable M. speciosa abuse and dependence. ...
... [17] These findings highlight the similarity of the underlying pharmacological mechanisms that mediate the discriminative stimulus for both drugs and translate well to studies in which humans report the plant having opioidlike effects. [6,11,30] The fact that mitragynine could substitute for morphine discriminative cue also supports human selfreported use as a substitute to opioids. [10] It is worth noting that the effects of mitragynine were partially blocked by naloxone which suggested that opioid receptors seem to be selectively involved in the discriminative stimulus effects induced by mitragynine. ...
Article
The plant Mitragyna speciosa Korth. is receiving increased attention as a therapeutic substitution for opioid use disorder (OUD). The active alkaloids constituents of the plant, particularly mitragynine and 7-hydroxymitragynine, have been shown to modulate opioid receptors, acting as agonists at mu-opioid receptors. Given this pharmacology, several studies have examined the abuse and dependence potential of M. speciosa and its alkaloids in various animal models of dependence. In addition to action on opioid receptors, the Mitragyna alkaloids also appear to exert diverse activities at other receptors in the central nervous system which may explain the complex pharmacological profile of these alkaloids. Hence, this review aims to provide an overview of the preclinical studies used to study M. speciosa dependence potential and describe recent progress made in assessing whether the plant or its active alkaloids can offer alternatives to opioids in the management of OUD. In conclusion, M. speciosa Korth. or its compound mitragynine may offer alternatives as a replacement therapy to opioid.
... 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. ...
Article
Full-text available
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.
... Mitragyna speciosa Korth, also known as kratom is a native medicinal plant that grows in Southeast Asia. It is commonly used as a safe herbal drug for pain relief, opioid dependence and withdrawal treatment as well as to alleviate psychological problems [8][9][10][11]. The leaves of this plant have been traditionally used as local analgesia and for opium treatment during the early 19th century in Malaya [12,13]. Rural folks commonly consumed kratom by chewing the fresh leaves, drying the leaves and ingesting it, or brewing it with tea/coffee and drinking it as a herbal solution [13]. ...
... The reinstatement of drug-seeking behaviour by MG could also indicate that the use of kratom may lead to relapse as opposed to assisting in the treatment of opioid addiction. However, further studies on kratom abuse and dependence are required as previous studies and reports have demonstrated various intensities of craving withdrawal with some users reporting a low craving and others expressing difficulty in abstaining [9,11,15]. Most of the kratom users also reported that kratom withdrawal symptoms are considered to be rather mild as compared to classical opioids, and the effects are also weaker than those observed following the discontinuation of opioids [15,20,30]. ...
Article
Kratom is a medicinal plant that exhibits promising results as an opiate substitute. However, there is little information regarding the abuse profile of its main psychoactive constituent, mitragynine (MG), particularly in relapse to drug abuse. Using the place conditioning procedure as a model of relapse, this study aims to evaluate the ability of MG to induce conditioned place preference (CPP) reinstatement in rats. To evaluate the cross-reinstatement effects, MG and morphine were injected to rats that previously extinguished a morphine-or MG-induced CPP. Following a CPP acquisition induced by either MG (10 and 30 mg/kg, i.p.) or morphine (10 mg/kg, i.p.), rats were subjected to repeated CPP extinction sessions. A low dose priming injection of MG or morphine produced a reinstatement of the previously extinguished CPP. In the second experiment of this study, a priming injection of morphine (1, 3 and 10 mg/kg, i.p.) dose-dependently reinstated an MG-induced CPP. Likewise, a priming injection of MG (3, 10 and 30 mg/kg, i.p.) was able to dose-dependently reinstate a morphine-induced CPP. The present study demonstrates a cross-reinstatement effect between MG and morphine, thereby suggesting a similar interaction in their rewarding motivational properties. The findings from this study also suggesting that a priming exposure to kratom and an opioid may cause relapse for a previously abused drug.
... 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]. ...
Article
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.
... Recent interest in the effects of M. speciosa has emerged within North America, western Europe, and Australia, largely due to its increased popularity and use (Swogger and Walsh, 2018). Although banned in Thailand in 1943 and Malaysia in 1953, sale and use of M. speciosa is legal throughout much of the United States where it is sold as an herbal dietary supplement to treat chronic pain and improve human health and performance (Singh et al., 2016). ...
... Recent increase in its use, coupled with a lack of M. speciosa product information, has likely contributed to increased reports of toxicity and mortality among users in the West, although reported deaths are associated with product adulterated with other, often toxic, compounds. (McWhirter and Morris, 2010;Nelsen et al., 2010;Swogger and Walsh, 2018). No such reports, however, have occurred in southeast Asia where is has long been used historically as an ethnobotanical herb (Singh et al., 2016). ...
... Another widely reported reason for kratom use is pain management [5][6][7]. Whereas fewer studies have examined kratom's use for negative mood states and conditions, a recent systematic review of 13 observational studies indicated that kratom is also being used to selftreat negative affect, most frequently anxiety and depression, with users reporting generally positive results [8]. Based on prior and recent studies involving kratom and similarities between kratom and several substances with antidepressant and antipsychotic properties, we examine literature germane to estimating kratom's potential utility as a treatment for psychiatric symptoms [9]. ...
... Although no clinical study has evaluated the antidepressant effects of kratom, or any of its constituents to date, several online and in-person surveys document the reasons and benefits that kratom users report [7,8,24,26,27]. In a 2016 online survey conducted among 8,049 current kratom users, 58% reported use for self-treatment of a mental or emotional disorder [24]. Among those taking kratom to self-treat a mental or emotional disorder, females were more likely to take kratom for such conditions, while those aged 41 or older were less likely to consume for these reasons. ...
Article
Full-text available
Mitragyna speciosa, otherwise known as kratom, is a plant in the coffee family (Rubiaceae) native to Southeast Asia and Thailand whose leaves have been shown to cause opioid-like and stimulant responses upon ingestion. The major pharmacologically active compounds present in kratom, mitragynine and 7-hydroxymitragynine (7-HMG), are both indole alkaloids and are responsible for its opioid-like activity. While kratom is most commonly known for its affinity for mu-opioid receptors, research has shown one of its active components has effects on the same receptors to which some antipsychotics bind, such as D2 dopamine, serotonin (5-HT2C and 5-HT7), and alpha-2 adrenergic receptors displaying possible indications of kratom to be used as both antipsychotics and antidepressants. Although studies to evaluate this effect are still lacking, several online and in-person surveys note relief of depression and anxiety symptoms among those who consume kratom products, and in fact identify it as a common reason for consumption. This then highlights the dire need for further research to be conducted on kratom, its mechanism of action and the constituents that elicit these antidepressant, anxiolytic, and antipsychotic properties.
... Several preclinical and clinical observations had indicated a potential therapeutic use of Kratom for the treatment of depression and anxiety disorders (Swogger and Walsh, 2018;Johnson et al., 2020). A functional dependence on Kratom emerged in the present case only after chronic well-controlled Kratom consumption failed to yield its effects. ...
... A particular risk of any Kratom instrumentalization is the establishment of a Kratom addiction and emerging cognitive deficits, as it was shown for Kratom and its main psychoactive alkaloids (Yusoff et al., 2016;Ismail et al., 2017;Hassan et al., 2019;Swogger and Walsh, 2018). Other case studies have also brought up cases of problematic Kratom use in Europe and the U.S., in particular in the self-management of severe pain Metastasio et al., 2020) or in the context of opiate (Boyer et al., 2007;Singh et al., 2020) or alcohol self-withdrawal (Havemann-Reinecke, 2011). ...
Article
Full-text available
Background Kratom is a psychoactive plant preparation originating from Southeast Asia. It has been used as a recreational and performance drug in Southeast Asia, and is now increasingly used in Europe and the U.S. Case report We describe the case of a 63-year-old man who presented for treatment after his long-term Kratom use failed as a self-management for persistent major depression (ICD 10: F33.2) and a generalized anxiety disorder (ICD-10: F41.1). The failure coincided with emerging stress at the beginning of the COVID-19 pandemic. The patient suffered from childhood on from ruminative thinking and depressive mood, which was treated in several settings during his life. He started to use alcohol to control his depression, but developed an alcohol addiction. This was successfully treated and the patient remained abstinent for more than 25 years afterwards. About 7 years ago, he started to use Kratom 3-4 times daily on a regular, but constant rate. Kratom use worked efficiently as a self-management of his depression with no escalation of dosing. It was also very effective in reducing Morbus Menière symptoms of tinnitus and sudden hearing loss, which eventually allowed regular performance as a caregiver in a demanding job on shift-work. During recently increased stress load in the work environment and the COVID-19 pandemic, the established Kratom doses failed to control hyperarousal and mental nervousness. The patient was treatment seeking and subsequently detoxified from Kratom. Anxiety- and depression management was shifted to treatment attempts with Lorazepam, Venlafaxine, Opipramol, Mirtazapine and psychotherapy. Conclusion Kratom instrumentalization for self-management of depression and anxiety may effectively work without causing escalation of drug use and addiction, but may be limited by a temporary increase in psychological stress load and a relapse into major depression and generalized anxiety disorder.
... 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. ...
Article
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.
... In Malaysia, Bhutan and Myanmar kratom is illegal, and in Indonesia it will be banned by 2022 (52). Discrepancies among the various legislations internationally, as well as the increase in the use of internet and globalization have resulted in an increased use of kratom for voluptuary purposes (53) indicating the need for international coordination of scientists and legislators (54). That kratom could induce an opioid-like withdrawal syndrome, therefore it can be included among addictive substances, is shown by the fact that it may be present in neonates exposed to the substance due to their mothers' heavy use during pregnancy (55)(56)(57)(58)(59)(60)(61). ...
... However, kratom withdrawal syndromes are usually mild and transient (72)(73)(74), similar to but milder than those of opiate withdrawal (74,75), but may be complicated in some users (54). ...
Article
Full-text available
Kratom or Mitragyna speciosa (Korth.) is an evergreen tree of the coffee family native to South-East Asia and Australasia. It is used by locals recreationally to induce stimulant and sedative effects and medically to soothe pain and opiate withdrawal. Its leaves are smoked, chewed, or infused, or ground to yield powders or extracts for use as liquids. It contains more than 40 alkaloids; among these, mitragynine and 7-hydroxymitragynine are endowed with variable mu, delta, and kappa opioid stimulating properties (with 7-hydroxymitragynine having a more balanced affinity), rhynchophylline, which is a non-competitive NMDA glutamate receptor antagonist, but is present in negligible quantities, and raubasine, which inhibits α1-adrenceptors preferentially over α2-adrenceptors, while the latter are bound by 7-hydroxymitragynine, while mitragynine counters 5-HT2A receptors. This complexity of neurochemical mechanisms may account for kratom's sedative-analgesic and stimulant effects. It is commonly held that kratom at low doses is stimulant and at higher doses sedative, but no cut-off has been possible to define. Long-term use of kratom may produce physical and psychological effects that are very similar to its withdrawal syndrome, that is, anxiety, irritability, mood, eating, and sleep disorders, other than physical symptoms resembling opiate withdrawal. Kratom's regulatory status varies across countries; in Italy, both mitragynine and the entire tree and its parts are included among regulated substances. We describe the case of a patient who developed anxiety and dysphoric mood and insomnia while using kratom, with these symptoms persisting after withdrawal. He did not respond to a variety of antidepressant combinations and tramadol for various months, and responded after 1 month of clomipramine. Well-being persisted after discontinuing tramadol.
... Consequently, Kratom currently remains legal and available in the United States, where individuals use Kratom to self-manage various health conditions such as pain, also in Covid-19 disease ( Metastasio et al., 2020 ), mental health problems (e.g. ADHD, mood and anxiety disorders), and opioid/alcohol addiction and/or withdrawal ( Bath et al., 2020 ;Garcia-Romeu et al., 2020 ;Swogger and Walsh, 2018 ). ...
... A state of opioid-like relaxation as well as other benefits that were more linked to the plant's psychostimulant (e.g., euphoria, increased sexual energy) and "entactogenic " properties, such as enhanced communication, were often reported. Such claims are supported by literature where Kratom use is associated with mood elevation, anxiolysis, enhanced socialisation and nootropic effects ( Bath et al., 2020 ;Swogger and Walsh, 2018 ), including in traditional settings, like Malaysia and Thailand, where the plant is commonly consumed for earning extra income and enhancing productivity ( Saingam et al., 2013 ). We also found the use of Kratom to 'taper off' opioids, manage withdrawal symptoms, or as a substitute subsistence dose to minimise the risk of relapse in those who were dependant on illicit substances, since Kratom is not addictive like opioids and manage to help them overcome their opioid, or Substance Use Disorder (SUD). ...
Article
Kratom (Mitragyna speciosa) is a tree native to Southeast Asia with long history of traditional medicinal use. The aim of this study was to investigate the nature of self-reported exported experiences as shared on YouTube™ videos. A total of 500 videos with 19,478,180 views and 134, 863 comments emerged from the data scrape extracted via the YouTube Data Tool. 12 out of the 16 most viewed videos emerged from our searches were manually processed and selected for inductive thematic analysis. Kratom use for the self-medication of a number of health conditions was described in the videos, including for opioid dependence/addiction (83.4%), pain (75%), anxiety (67%) and depression (42%), substance use problems (42%) as well as for energy boosting (50%), mood elevation (25%) and nootropic effects (25%). Although most of the described experiences were positive (58%), side-effects such as dependence and withdrawal (50%), nausea (42%), loss of appetite (25%), sedation (25%), loss of motivation (16.7%), headache (16.7%), drowsiness (16.7%), dry mouth and frequent urination (16.7%) were also reported and associated in 25% of the cases to chronic ingestions. Overall, our findings would show that Kratom is used more frequently for self-medication, than as a recreational drug. It also supports the need for more controlled clinical studies to better assess the safety and the efficacy of its use in a therapeutic context.
... Even though kratom has been used in Southeast Asia for generations, it is only over the past 25 years that kratom use has expanded to Europe and North America [1,2,4,[12][13][14]. In the US, kratom products are used extensively for the self-management of pain, depression and opioid use disorders [15][16][17][18]. The most widely used products include chopped, dried leaf material (either alone or in capsule or tablet form) or concentrated extracts that are formulated as liquids or capsules [2,12,19]. ...
Article
Full-text available
Kratom (Mitragyna speciosa, Korth) is a tree-like plant 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. Recently, the United States Food and Drug Administration and Centers for Disease Control have raised concerns regarding the contamination of some kratom products with toxic metals (Pb and Ni) and microbes such as Salmonella. To further explore this issue, eight different kratom products were legally purchased from various “head”/”smoke” shops in the Western Suburbs of Chicago and then tested for microbial burden, a panel of metals (Ni, Pb, Cr, As, Hg, Cd), and levels of the main psychoactive alkaloid mitragynine. All of the samples contained significant, but variable, levels of mitragynine (3.9–62.1 mg/g), indicating that the products were, in fact, derived from kratom. All but two of the samples tested positive for the presence of various microbes including bacteria and fungi. However, none of the samples tested positive for Salmonella. Seven products showed significant levels of Ni (0.73–7.4 µg/g), Pb (0.16–1.6 µg/g) and Cr (0.21–5.7 µg/g) while the other product was negative for metals. These data indicate that many kratom products contain variable levels of mitragynine and can contain significant levels of toxic metals and microbes. These findings highlight the need for more stringent standards for the production and sale of kratom products.
... Many extensive surveys have reported kratom's beneficial effects in reducing pain and managing opioid dependence and physical withdrawal [5,6,7]. As a new herbal alternative, kratom has attracted attention from researchers worldwide and is used widely by people or patients who are dependent on prescription and illicit opioid use [8,9,10]. However, kratom use may also cause substance dependence, where a number of users reported experiencing negative effects associated with physical and emotional symptoms of ...
Article
Kratom (Mitragyna speciosa Korth) is a plant species currently used as an alternative self-treatment for pain and management of opioid dependence and withdrawal. However, information on the effect of its negative emotional state of withdrawal, particularly of the main psychoactive constituent, mitragynine (MG) is still lacking. The present study was designed to determine whether naloxone-precipitated MG withdrawal is associated with increased anxiety-like behaviour in both open-field test (OFT) and elevated-plus maze (EPM) test. Male Sprague Dawley rats were administered with MG and morphine twice daily for 14 consecutive days to develop substance dependence. The withdrawal was precipitated on day fifteen using naloxone (2 mg/kg, i.p.). This study has exhibited that challenge with opioid antagonist naloxone did not result in reliable expression of anxiety behaviour following chronic MG exposure in OFT and EPM tests. However, several somatic signs of withdrawal were observed in naloxone-precipitated MG withdrawn rats. The findings of this study suggest that rat behaviours during OFT and EPM tests might not be driven solely by anxiety levels following naloxone-precipitated withdrawal but rather by other withdrawal-induced behaviours. The presence of somatic signs in naloxone-precipitated MG withdrawn rats was the piece of evidence to prove that that discontinuation of MG or kratom is associated with physical symptoms of withdrawal. However, further studies are prompted to evaluate MG or kratom withdrawal severity to justify its use as opioid replacement therapy.
... Some of these substances include fentanyl, heroin, and other prescription opioids [21]. Despite its use for various purposes, an absence of evidence supports the many purported benefits of kratom [7,17,22]. Much of the information available about kratom is based on anecdotal reports, user experiences, and case studies [19]. ...
Article
Full-text available
Background Amid a Canadian opioid crisis, many have turned to natural health products, such as kratom ( Mitragyna speciosa ), to manage their opioid withdrawal. Kratom has also been reported to relieve anxiety, improve stamina, and heighten physical performance. Given that kratom is not authorized for sale by Health Canada, many have turned to online retailers to purchase kratom due to its easy accessibility online. This study investigated the quality of consumer health information provided on the websites of online vendors selling kratom to consumers in Canada. Methods Following searches on Google.ca using search terms designed to simulate the information-seeking behaviour of a typical patient-user online, eligible websites were assessed using the 16-question DISCERN instrument, a tool designed to assess the quality of consumer health information. Searches were conducted on March 27, 2020 and only websites presenting information in English were included. Results A total of 200 webpages were identified; after screening based on eligibility criteria and combining different webpages that belonged to the same website, 51 websites were found to be eligible. The mean summed DISCERN score across all 51 websites was 36.95 (SD = 2.44) out of 75, which reflects poor quality consumer health information across the subset of websites. The overall quality of websites was poor, as 78% ( n = 40) of vendors received a score of 2 or less out of 5. Conclusions Individuals who seek information about kratom online are frequently exposed to poor quality consumer health information. Those looking to purchase kratom online are not provided with the critical information necessary to make an informed decision regarding its use, such as the complete details about the risks and side effects or a description of how kratom affects the body. Given the growing interest in kratom, knowledge of the quality of information available can lead to improved dialogue between healthcare providers and patients.
... [13] The rise in kratom sales in the United States is due in part to multiple websites marketing the leaves as alternative treatment for reducing chronic pain and managing opioid withdrawal. [14,15] Pharmacological analysis shows that kratom contains the alkaloids mitragynine and 7-hydroxymitragynine, which interact with opioid receptors [16,17] and render morphinelike effects. [18] Currently, kratom is not controlled under the Federal Controlled Substances Act, but is labeled a Drug and Chemical of Concern. ...
Article
Aim: To analyze the knowledge of dental patients in an urban setting regarding the legality and potential clinical benefits of marijuana and kratom. Materials and Methods: This presented cross-sectional study had 18-item questionnaire consisting of four demographic questions, six questions focused on marijuana, and eight questions focused on kratom, which was distributed in paper and pencil format to a convenience sample of 400 dental patients in the waiting area of an urban dental school. Data were entered into Qualtrics Research Suite software and analyzed using descriptive statistics and χ2 test with significance at P 0.05. Results: Four hundred (400) surveys were completed anonymously by adult volunteers. Results showed a variable level of knowledge regarding the legality and potential clinical use of marijuana and tetrahydrocannabinol (THC). With some questions, a statistically significant difference in knowledge was observed relative to age and highest level of education of the respondent. In contrast, compared to any knowledge of marijuana, respondents had little to no knowledge of kratom or mitragynine legality, health benefits, or potential as a substitute for opioids. Conclusion: Knowledge of marijuana is to be expected as its widespread use and debates of its legality have been in the public eye for years in the United States. Although similar debates regarding whether kratom should be legal continue, this survey suggests that the public has little to no knowledge of what it is. As opioid use disorder increases, so does the search for opioid substitutes. It is important that the public be made aware of potential opioid substitutes other than marijuana so that personal choices and decisions can be made with current and correct information. © 2020 Journal of International Oral Health | Published by Wolters Kluwer - Medknow.
... Various internet studies found that some kratom users are concerned about the possibility of relapsing to opioids and/or seeking alternative, possibly questionable, sources of kratom if products become less readily available. This is a serious concern as kratom, not currently regulated as a dietary supplement, may be adulterated by unscrupulous traders and cause users to relapse to opioid use and inevitably experience a significant increase in overdose risk (7,9,(14)(15)(16)(17). Indeed, there is evidence to suggest that the COVID-19 pandemic has been associated with increased drug overdose deaths and that the reduced access to conventional treatment, as well as mutual-aid groups, is a plausible contributing factor (18), though it is unknown whether diminished access to kratom has explicitly contributed to any overdose deaths. ...
Article
Full-text available
Kratom ( Mitragyna speciosa Korth., Rubiaceae) is native to and has traditional use in Southeast Asia. The number of kratom users outside of Southeast Asia has increased significantly in recent decades with use spreading to the Unites States (US) and Europe. Because of its reputed opioid-like psychoactive effects at higher doses, kratom has been regulated in several countries and is subject to an import ban by the US Food and Drug Administration. Nonetheless, in the US it is estimated that 10–15 million people consume kratom primarily for the self-treatment of pain, psychiatric disorders, to mitigate withdrawal from or dependence on opioids, and to self-treat opioid use disorder or other substance use disorders (SUDs). Due to the global COVID-19 pandemic, a shortage in the supply of kratom products may place unexpected burdens on kratom users, potentially influencing some who use kratom for SUD self-treatment to regress to harmful drug use, hence increasing the likelihood of adverse outcomes, including overdose. Inadequate treatment, treatment barriers, and increases in the sales of adulterated kratom products on the internet or in convenience stores could exacerbate circumstances further. Although there are currently no verified indications of kratom scarcity, researchers and clinicians should be aware of and remain vigilant to this unanticipated possibility.
... In this context, we became interested in the psychoactive plant Mitragyna speciosa that has been used for centuries in Southeast Asia for treatment of pain, fatigue, opium dependence, and a number of other ailments. In the US, the use of the dry leaf material, known as "kratom", has been on the rise in the last decade, along with the number of anecdotal reports that point to the efficacy of kratom in a range of disorders with limited therapeutic options, including opioid dependence, treatment-resistant depression, anxiety, and pain syndromes [5][6][7][8][9][10][11][12] . A number of alkaloids in this plant, including mitragynine (MG) and its oxidation product 7-hydroxymitragynine (7OH, Fig. 1), have been found to bind to opioid receptors and represent molecular scaffolds for the development of opioid receptor modulators 13,14 . ...
Article
Full-text available
Mitragynine (MG) is the most abundant alkaloid component of the psychoactive plant material “kratom”, which according to numerous anecdotal reports shows efficacy in self-medication for pain syndromes, depression, anxiety, and substance use disorders. We have developed a synthetic method for selective functionalization of the unexplored C11 position of the MG scaffold (C6 position in indole numbering) via the use of an indole-ethylene glycol adduct and subsequent iridium-catalyzed borylation. Through this work we discover that C11 represents a key locant for fine-tuning opioid receptor signaling efficacy. 7-Hydroxymitragynine (7OH), the parent compound with low efficacy on par with buprenorphine, is transformed to an even lower efficacy agonist by introducing a fluorine substituent in this position (11-F-7OH), as demonstrated in vitro at both mouse and human mu opioid receptors (mMOR/hMOR) and in vivo in mouse analgesia tests. Low efficacy opioid agonists are of high interest as candidates for generating safer opioid medications with mitigated adverse effects.
... Differences in preparation and use have likely contributed to reports of toxicity and mortality among new users in the United States and Europe. Deaths attributed to kratom use, however, are often associated with product adulteration or consumption with other, often toxic, compounds (McWhirter and Morris, 2010;Nelsen et al., 2010;Lydecker et al., 2016;Swogger and Walsh, 2018). Interestingly, no reports of mortality among kratom users have occurred in Southeast Asia where it has a long history of use. ...
Article
Full-text available
Leaves harvested from the Southeast Asian tree Mitragyna speciosa (kratom) have a history of use as a traditional ethnobotanical source of medicine to combat fatigue, improve work productivity, and to reduce opioid-related withdrawal symptoms. Kratom leaves contain an array of alkaloids thought to be responsible for the bioactivity reported by users. Interest in the consumptive effects of kratom has led to its recent popularity and use in North America, Western Europe, and Australia. Although the chemistry and pharmacology of select kratom alkaloids are understood, studies have not examined the influence of production environment on growth and alkaloidal content. To directly address this need, 68 kratom trees were vegetatively propagated from a single mother stock to reduce genetic variability and subjected to four varying fertilizer application rates. Leaves were analyzed for chlorophyll concentration, biomass, and alkaloidal content to understand the physiological response of the plant. While increasing rates of fertilizer promoted greater plant growth, relationships with alkaloidal content within leaves were highly variable. Fertility rate had little influence on the concentration of mitragynine, paynantheine, speciociliatine, mitraphylline, and corynoxine per leaf dry mass. 7-Hydroxymitragynine was below the lower limit of quantification in all the analyzed leaf samples. Low to medium rates of fertilizer, however, maximized concentrations of speciogynine, corynantheidine, and isocorynantheidine per leaf dry mass, suggesting a promotion of nitrogen allocation for secondary metabolism occurred for these select alkaloids. Strong correlations (r2 = 0.86) between extracted leaf chlorophyll and rapid, non-destructive chlorophyll evaluation (SPAD) response allowed for development of a reliable linear model that can be used to diagnose nutrient deficiencies and allow for timely adjustment of fertilization programs to more accurately manage kratom cultivation efforts. Results from this study provide a greater understanding of the concentration and synthesis of nine bioactive alkaloids in fresh kratom leaves and provide foundational information for kratom cultivation and production.
... 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). ...
Article
Full-text available
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.
... 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). ...
Article
Full-text available
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.
... Tremore e anoressia con calo del peso possono presentarsi nel consumo cronico. L'uso continuativo può produrre tolleranza, e un'interruzione repentina sintomi d'astinenza 97 . ...
... 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). ...
Article
Full-text available
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.
... Such theories may account for the low incidence of kratom use disorder and other side effects among traditional users in Southeast Asia [81][82][83][84][85]. Nevertheless, the successful instrumentation of kratom does not preclude the potential for prolonged drug use, which under certain circumstances can degenerate into outright addiction [78]. It has also been proposed that a significant amount of kratom use occurs as a substitute for more harmful substances (namely narcotics) in patients with existing substance abuse, in which case kratom use represents a sort of harm reduction rather than drug abuse [79,86]. Yet, while there is convincing evidence that kratom has significantly less potential for dependence and overdose than traditional opioids, the use of kratom in place of established medical opioid replacement regimens has little basis in evidence [30, 87,88]. ...
Article
Kratom, or Mitragyna, is a tropical plant indigenous to Southeast Asia, with unique pharmacological properties. It is commonly consumed by preparing the leaves into decoction or tea, or by grinding them into a powder. Recent evidence has revealed that kratom has physiological effects similar to opioids, including pain relief and euphoria, as well as stimulant properties, which together raise potential concern for dependence and addiction. Moreover, growing evidence suggests that the prevalence of kratom use is increasing in many parts of the world, raising important considerations for healthcare providers. This manuscript will discuss the most current epidemiology, pharmacology, toxicity, and management related to kratom, while seeking to provide a contemporary perspective on the issue and its role in the greater context of the opioid epidemic.
... 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]. ...
Article
Full-text available
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.
Article
Kratom, or Mitragyna speciosa Korth., is a tropical plant prevalent in Southeast Asia, and it is utilized as a traditional remedy for symptomatic relief of various illnesses. It has been labeled as an atypical opioid with significant narcoticlike properties, capable of inducing kratom dependence among those who misuse or abuse it. The prevalence of kratom use has drastically increased worldwide, raising concerns among healthcare providers, particularly regarding the availability of efficacious treatment options for kratom dependence. This manuscript provides a comprehensive narrative review of literature focusing on the psychoactive alkaloids of kratom, the possible neurobiological and pathophysiological models underlying the occurrence of kratom dependence, and the clinical presentations and effective treatment options available for kratom dependence. The psychoactive alkaloids of kratom, such as mitragynine (MG) and 7-hydroxymitragynine (7-HMG), act as partial mu opioid agonists and induce kratom dependence. As a result, regular kratom use leads to withdrawal symptoms on abstinence, along with craving, tolerance, and cross-tolerance to morphine. The psychological withdrawal symptoms reported include depressed mood, anxiety, restlessness, irritability, and feeling tense, while the physical withdrawal symptoms are myalgia and body ache, joint pain, lacrimation, running nose, yawning, insomnia, diarrhea, feverish sensation, loss of appetite, tremors, itching over the body, loss of concentration, and chills. Neonatal withdrawal symptoms, such as oral intolerance, restlessness, irritability, and vomiting, are also reported in newborns of women who are on regular kratom use. Sublingual buprenorphine-naloxone (Suboxone) is reported as a promising treatment for detoxification and maintenance replacement therapy for kratom-dependent users. Alternative treatments for in-patient detoxification include intravenous clonidine and a combination of oral dihydrocodeine and lofexidine. We conclude by adding a note on the research gap concerning kratom dependence, which future studies should focus on.
Article
Out-of-treatment HIV positive opiate users often engage in risky injecting and sexual behaviors. We sought the self-reported experiences on whether or not kratom (Mitragyna speciosa Korth.) use was associated with a reduction in HIV risk behaviors among them. A convenience sample consisting of thirty-two HIV positive opiate users participated in the study. Of this, three-fifths (n = 20/32) used kratom to suppress opiate withdrawal, increase energy, as a heroin substitute, to reduce heroin dependence and self-treat psychological problems. More than one-third (38%) in the sample claimed that kratom use reduced their risky injecting and sexual behaviors. Given the small sample size, the perceived association between kratom use and the reduction in HIV risk behaviors could not be established more convincingly. However, the findings provide the basis for a broader-based study to evaluate the potential of kratom in curtailing HIV risk behaviors among HIV positive opiate users.
Article
Background: Interest in the Southeast Asian natural remedy kratom has increased in Western countries recently, along with increasing concern over its potential toxic effects. Objective: To describe and compare demographics, common co-exposure substances, clinical effects, treatments, and medical outcomes of kratom “abuse” exposures in the United States (US) and Thailand. Methods: This is a retrospective analysis of kratom “abuse” exposures, defined as use when attempting to gain a psychotropic effect, reported to the National Poison Data System (NPDS) in the US and the Ramathibodi Poison Center (RPC) in Thailand from 2010 to 2017. Multivariate analysis identified risk factors for severe medical outcomes, defined as both ICU admissions and death. Results: Nine-hundred-twenty-eight cases were included (760 from NPDS and 168 from RPC). A greater proportion of cases involved co-exposures in Thailand (64.8% versus 37.4%; odds ratio [OR] = 3.10, 95% confidence interval [CI] = 2.15–4.47, p < .01). Both countries had a similar prevalence of opioid and benzodiazepine co-ingestions, but the US had more co-ingestions with other sedatives (4.6% versus 0%, OR = 0, 95% CI = 0–0.47, p < .01). Common clinical effects included tachycardia (30.4%), agitation/irritability (26.2%), and drowsiness/lethargy (21.1%). Six deaths occurred, including one single-substance exposure in the US, three multiple-substance exposures in the US, and two multiple-substance exposures in Thailand. IV fluid administration was provided more frequently in the US (OR = 18.82, 95% CI = 5.85–60.56, p < .01). Conclusions: Despite lower frequencies of co-ingestants overall, US kratom abuse exposures yielded greater clinical severity. This disparity may be attributable to differences in the products labeled “kratom,” greater sedative co-exposures in the US, and/or differences in population genetics or use patterns.
Article
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.
Article
Mitragynine (MG), the most prevalent bioactive alkaloid in kratom, displays nanomolar affinity for µ, κ and δ opioid receptors and produces opioid-dependent antinociception and dependence in rats. Here, using a battery of behavioral assays, we investigated MG effects in planarians. Acute MG exposure (< 100 μM) did not affect planarian motility or environmental preference, but reduced motility was detected during abstinence from chronic MG (1, 10 μM). MG (10 μM) produced place conditioning effects that were reduced by naltrexone (10 μΜ). These results suggest that MG produces opioid-sensitive reinforcing effects in planarians and MG pharmacology is conserved across different species.
Article
There are several medical drug addict treatment methods used by physicians and other health professionals worldwide. The community-based treatment and care for drug use and dependence have increased in popularity. However, little is known about whether or how Islamic spirituality model could be incorporated into formal treatment in the Muslim community. This study aimed to explore the Islamic integrated model for drug addict treatment and rehabilitation on Kratom use among Muslim adolescents in Krabi Province, Thailand. The focus group discussion and in-depth interview were carried out in chief officer, the staff of treatment service volunteers, program leaders, and families and friends of addicts during October 2017-December 2018. The results revealed that the implementation of integrated Islamic religious learning in the drug therapy session to grow the spiritual religiosity and lower relapse among Muslim youth who were previous kratom addicts. The Islamic faith-based treatment model could be declared the evidence of kratom recovery in community level.
Article
Background:Kratom (Mitragyna speciosa Korth.) is a medicinal plant, widely used in Southeast Asia chiefly for its unique medicinal properties in treating chronic pain, opioid dependence and withdrawal, and as a mood enhancer.Method:Relevant articles describing kratom's medicinal utility was identified and reviewed.Results:In traditional settings, laborers chew fresh leaves or ingest a kratom decoction (tea) as a stimulant that increases work performance, while those with opioid use disorder (OUD) use kratom as an affordable substitute for opioids. Though kratom is alleged to cause adverse health effects if used frequently over prolonged periods, its use has not been linked to any major health threat in traditional settings.Conclusion:Currently, kratom’s pharmacological and long-term safety profile remains poorly elucidated and warrants further research. This paper provides a brief account of possibly overlooked medicinal potential of kratom.
Article
Background: Kratom is a substance that when ingested produces an opioid-like effect. As kratom continues to gain popularity, increasing numbers of cases of addiction, dependence, and adverse events have been reported, as well as an increase in mortality associated with its use. George E. Wahlen Department of Veterans Affairs Medical Center has been using buprenorphine/naloxone for the treatment of kratom withdrawal and dependence in both primary care and specialty addiction treatment settings in the Veteran population. Cases: We present three cases that describe the use of buprenorphine/naloxone for kratom dependence. For each case, we describe the withdrawal symptoms from kratom, induction and long-term maintenance on buprenorphine/naloxone in kratom dependence, the impact of polysubstance use disorders in management of kratom dependence, and the use of urine drug screens for kratom alkaloids during treatment. Discussion: This case series demonstrates that patients with kratom dependence can effectively be treated with buprenorphine/naloxone. It appears that it is safe to induce buprenorphine/naloxone as early as eight hours after last kratom use and maintenance dosing for kratom use was similar to maintenance doses used in opioid use disorder. Prolonged and continued withdrawal symptoms were reported despite treatment with buprenorphine/naloxone and multiple daily doses of up to 24mg per day may be beneficial for prolonged withdrawal symptoms and for cooccurring pain. Polysubstance use with kratom dependence may require higher levels of care and higher doses of buprenorphine/naloxone. Urine drug screens may be best practice for monitoring kratom alkaloids concentrations and facilities that utilize buprenorphine/naloxone to treat kratom dependence should have testing available. Further research is needed on the impact and the treatment of kratom dependence.
Article
Kratom ingestion for its psychotropic effect or to self-treat opioid withdrawal symptoms has increased over the last 10 years in the United States. Although mild adverse effects have been observed in users, reports of respiratory failure and shock after kratom consumption remain rare. In this case, a 35-year-old man initially presented to the emergency department with profound circulatory shock, metabolic acidosis, hypoxia, and symptoms of autonomic nervous system dysfunction. The patient required vasopressor support, multiregimen sedation and rapid sequence intubation, mechanical ventilation, and emergent hemodialysis. Within 72 hours, the patient's condition stabilized, and he was extubated. The patient reported regular consumption of large quantities of kratom as well as injection of heroin and cocaine. In this report, a rare clinical presentation after kratom ingestion is described.
Article
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.
Article
Background: In recent years, use of the herbal supplement kratom has increased in the United States. The reasons for use include pain relief, particularly as a substitute for opioids. Objectives: To describe epidemiologic trends in kratom-related exposures among older adults reported to U.S. poison centers. Design: Retrospective analysis of American Association of Poison Control Center's National Poison Data System (NPDS). Setting: Data from all U.S. poison centers from 2014 to 2019 were examined. Participants: Kratom exposure cases involving adults aged 18 and older. Kratom cases were identified by product and NPDS generic codes. Non-human and information-only calls were excluded. Data were examined for all calls for exposures among adults, with a focus on older adults aged 60-69 years and above 70 years. Measurements: Descriptive analyses were used to characterize individual demographic, exposure information, clinical effects, and medical outcomes associated with kratom exposures among older adults. Comparisons across age groups (18-59, 60-69, and 70+ years) were made using Fisher's exact tests. Results: Among 3484 kratom-related exposures reported between 2014 and 2019, 4.6% (n = 162) were among adults over 60 years. The number of kratom-related exposures increased over time. Most cases originated with calls from healthcare facilities (81.1%) and involved kratom as a single ingestant (63.0%). The reason for most ingestions was intentional (74.5%). One in five exposures among adults aged 70 and older involved an adverse reaction (e.g., drug interaction; 21.9%), compared with 12.3% among ages 60-69 and 9.6% among ages 18-59 years. Neurological and cardiovascular clinical effects were observed. Twenty-three deaths were observed among older adults. Conclusion: Healthcare providers and older adult patients should be aware of the potential risks of kratom use, including medication interactions and falls. When reviewing medication lists, providers should query this population for all medications and substances being used, especially in people being treated for pain.
Book
Full-text available
Psychiatry Trainees’ Attitudes, Knowledge, and Training in Addiction Psychiatry—A European Survey
Article
Background: Mitragyna speciosa, referred to as "kratom", is increasingly used in the United States for self-treating pain, psychiatric, and substance use disorder symptoms. It is used by some to attenuate opioid withdrawal and as a longer-term drug substitute. Most self-report data have come from online surveys, small in-person surveys, and case reports. These may not be representative of the broader kratom-using population. Purpose: Analyze user-generated social media posts to determine if independent, descriptive accounts are generally consistent with prior U.S. kratom survey findings and gain a more nuanced understanding of kratom use patterns. Methods: Reddit posts mentioning kratom from 42 subreddits between June 2019-July 2020 were coded by two independent raters. Findings: Relevant posts (number of comments, upvotes, and downvotes) from 1274 posts comprised the final sample (n = 280). Of the 1521 codes applied, 1273 (83.69%) were concordant. Desirable kratom effects were described among a majority, but so too were adverse effects. Reports of kratom as acute self-treatment for opioid withdrawal were more prominent compared to longer-term opioid substitution. Quantitative analysis found higher kratom doses associated (p < .001) with greater odds of reported kratom addiction (OR = 3.56) or withdrawal (OR = 5.88), with slightly lower odds of desirable effects (OR = 0.53, p = .014). Despite perceived therapeutic benefits, kratom was characterized by some in terms of addiction that, in some cases, appeared dose-dependent. Polydrug use was also prominently discussed. Conclusions: Results validated many prior survey findings while illustrating complexities of kratom use that are not being fully captured and require continued investigation.
Article
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
Article
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.
Article
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.
Article
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.
Article
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.
Article
The psychoactive plant kratom is a native plant to Southeast Asia, and its major bioactive alkaloid is mitragynine. Mitragynine exerts its analgesic properties by acting on the opioid receptors. One of its active metabolites, 7-hydroxymytraginine, is found to be 40 times more potent than mitragynine and 10 times more potent than morphine. Interestingly, current research suggests that mitragynine behaves as an atypical opioid agonist – possessing analgesic activity with less severe side effects than typical opioids. Although Thailand and Malaysia have criminalized the use, possession, growing, or selling of kratom due to its abuse potential, kratom still remains unregulated in the United States. The U.S. Drug Enforcement Agency (DEA) listed kratom as a “drug of concern” in 2008 with the intent to temporarily place mitragynine and 7-hydroxymitragynine onto Schedule I of the Controlled Substances Act. However, responses from the general public, U.S. Congress, and Kratom Alliances had the DEA retract their intent. Kratom is currently marketed in the U.S. as a dietary or herbal supplement used to treat chronic pain, anxiety, and depression with over $207 million in annual sales in the U.S. alone. Here, we will review the traditional and medicinal uses of kratom along with the synthesis of its bioactive ingredients, their pharmacology, metabolism, and structure-activity relationships. The importance in society of this currently controversial substance will also be discussed.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
A 24-year-old man whose medical history was significant for alcohol abuse and depression was found unresponsive in bed. He had several prior suicide attempts with 'pills' and had also been hospitalized for an accidental overdose on a previous occasion. Autopsy findings were unremarkable apart from pulmonary edema and congestion, and urinary retention. Postmortem peripheral blood initially screened positive for mitragynine 'Kratom' (by routine alkaline drug screen by gas chromatography-mass spectrometry, GC-MS), which was subsequently confirmed by a specific GC-MS selective ion mode analysis following solid-phase extraction. Concentrations were determined in the peripheral blood (0.23 mg/L), central blood (0.19 mg/L), liver (0.43 mg/kg), vitreous (<0.05 mg/L), urine (0.37 mg/L) and was not detected in the gastric. Therapeutic concentrations of venlafaxine, diphenhydramine and mirtazapine were also detected together with a negligible ethanol of 0.02% (w/v). The results are discussed in relation to previous cases of toxicity, and the lack of potential for mitragynine postmortem redistribution. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
Kratom (Mitragyna speciosa) is a plant indigenous to Thailand and Southeast Asia. Kratom leaves produce complex stimulant and opioid-like analgesic effects. In Asia, kratom has been used to stave off fatigue and to manage pain, diarrhea, cough, and opioid withdrawal. Recently, kratom has become widely available in the United States and Europe by means of smoke shops and the Internet. Analyses of the medical literature and select Internet sites indicate that individuals in the United States are increasingly using kratom for the self-management of pain and opioid withdrawal. Kratom contains pharmacologically active constituents, most notably mitragynine and 7-hydroxymitragynine. Kratom is illegal in many countries. Although it is still legal in the United States, the US Drug Enforcement Administration has placed kratom on its "Drugs and Chemicals of Concern" list. Physicians should be aware of the availability, user habits, and health effects of kratom. Further research on the therapeutic uses, toxic effects, and abuse potential of kratom and its constituent compounds are needed.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
Cognitive-behavioral therapy (CBT) is frequently used for various adult anxiety disorders, but there has been no systematic review of the efficacy of CBT in randomized placebo-controlled trials. The present study meta-analytically reviewed the efficacy of CBT versus placebo for adult anxiety disorders. We conducted a computerized search for treatment outcome studies of anxiety disorders from the first available date to March 1, 2007. We searched MEDLINE, PsycINFO, PubMed, Scopus, the Institute of Scientific Information, and Dissertation Abstracts International for the following terms: random*, cognitive behavior*therap*, cognitive therap*, behavior*therap*, GAD, generalized anxiety disorder, OCD, obsessive compulsive disorder, social phobia, social anxiety disorder, specific phobia, simple phobia, PTSD, post-traumatic stress disorder, and acute stress disorder. Furthermore, we examined reference lists from identified articles and asked international experts to identify eligible studies. We included studies that randomly assigned adult patients between ages 18 and 65 years meeting DSM-III-R or DSM-IV criteria for an anxiety disorder to either CBT or placebo. Of 1165 studies that were initially identified, 27 met all inclusion criteria. The 2 authors independently identified the eligible studies and selected for each study the continuous measures of anxiety severity. Dichotomous measures reflecting treatment response and continuous measures of depression severity were also collected. Data were extracted separately for completer (25 studies for continuous measures and 21 studies for response rates) and intent-to-treat (ITT) analyses (6 studies for continuous measures and 8 studies for response rates). There were no significant differences in attrition rates between CBT and placebo. Random-effects models of completer samples yielded a pooled effect size (Hedges' g) of 0.73 (95% CI = 0.88 to 1.65) for continuous anxiety severity measures and 0.45 (95% CI = 0.25 to 0.65) for depressive symptom severity measures. The pooled odds ratio for completer treatment response rates was 4.06 (95% CI = 2.78 to 5.92). The strongest effect sizes were observed in obsessive-compulsive disorder and acute stress disorder, and the weakest effect size was found in panic disorder. The advantage of CBT over placebo did not depend on placebo modality, number of sessions, or study year. Our review of randomized placebo-controlled trials indicates that CBT is efficacious for adult anxiety disorders. There is, however, considerable room for improvement. Also, more studies need to include ITT analyses in the future.
Article
Background: Kratom preparations have raised concerns of public health and safety in the US. Investigation into the demographics, perceived beneficial and detrimental effects of Kratom as well as common doses and purposes of its use are important to properly evaluate its potential health impact. Methods: An anonymous cross-sectional online survey was conducted in October 2016 of 10,000 current Kratom users through available social media and online resources from the American Kratom Association. A total of 8049 respondents completed the survey. Results: Kratom is primarily used by a middle-aged (31-50 years), middle-income ($35,000 and above) population for purposes of self-treating pain (68%) and emotional or mental conditions (66%). Kratom preparations present with a dose-dependent effect with negative effects, which were primarily gastrointestinal related including nausea and constipation, mainly presenting at high (5g or more/dose) and more frequent (22 or more doses/week) dosing. Conclusions: Kratom shows a dose-dependent opioid-like effect providing self-reported perceived beneficial effects in alleviating pain and relieving mood disorders. Kratom was primarily used for self-treatment of pain, mood disorders, and withdrawal symptoms associated with prescription opioid use.
Article
Background: Finding an effective, non-pharmacological approach to treat opioid withdrawal could remove some of the barriers associated with pharmacotherapy. The BRIDGE® is a noninvasive, percutaneous electrical nerve field stimulator developed to target pain. Objectives: This pilot study aimed to determine (1) the effects of the BRIDGE on withdrawal scores during the induction phase of opioid withdrawal therapy, (2) the percentage of subjects who successfully transitioned to medication assisted therapy (MAT). Methods: Adult patients treated with the BRIDGE during medically supervised withdrawal were included in this open label, uncontrolled, and retrospective study. The clinical opioid withdrawal scale (COWS) scores were prospectively recorded at different intervals (20, 30, and 60 min) and analyzed retrospectively. A subset of patients had scores recorded 5-days post-BRIDGE. Those who returned to the clinic and received their first dose of maintenance medication were considered to be successfully transitioned. Results: In this cohort (n=73), 65% were male. The mean COWS score prior to BRIDGE placement was 20.1 (±6.1). Twenty minutes after BRIDGE placement, the mean score was reduced to 7.5 (±5.9) (62.7% reduction, p<0.001). The scores further decreased after 30 minutes 4.0 (±4.4) and 60 minutes 3.1 (±3.4) (84.6% reduction, p<0.001). No rescue medications were administered during this period. The mean withdrawal score on day 5 was 0.6 (97.1% reduction, p<0.001) (n=33). Overall, 64/73 patients (88.8%) successfully transitioned to MAT. Conclusions: Neurostimulation with the BRIDGE is associated with a reduction in opioid withdrawal scores. This effect persisted during the induction period and allowed for effective transition to MAT.
Article
Objectives: The aim of this study is to review the effectiveness of third wave mindfulness-based cognitive behavioral therapies (CBTs) for depressive or anxiety symptomatology in older adults across a wide range of physical and psychological conditions. Methods: Electronic literature databases were searched for articles, and random-effects meta-analysis was conducted. Results: Ten studies met the inclusion criteria, of which nine reported the efficacy of interventions on depressive symptoms and seven on anxiety symptoms. Effect-size estimates suggested that mindfulness-based CBT is moderately effective on depressive symptoms in older adults (g = 0.55). The results demonstrated a similar level of overall effect size for anxiety symptoms (g = 0.58). However, there was a large heterogeneity, and publication bias was evident in studies reporting outcomes on anxiety symptoms, and thus, this observed efficacy for late-life anxiety may not be robust. The quality of the included studies varied. Only one study used an active psychological control condition. There were a limited number of studies that used an intent-to-treat (last observation carried forward method) analysis and reported appropriate methods for clinical trials (e.g., treatment-integrity reporting). Conclusions: Third wave mindfulness-based CBT may be robust in particular for depressive symptoms in older adults. We recommend that future studies (i) conduct randomized controlled trials with intent-to-treat to compare mindfulness-based CBT with other types of psychotherapy in older people and (ii) improve study quality by using appropriate methods for checking treatment adherence, randomization, and blinding of assessors. Copyright © 2016 John Wiley & Sons, Ltd.
Article
This review considers the potential influences of the use of cannabis for therapeutic purposes (CTP) on areas of interest to mental health professionals, with foci on psychological intervention and assessment. We identified 31 articles relating to CTP use and mental health, and 29 review articles on cannabis use and mental health that did not focus on use for therapeutic purposes. Results reflect the prominence of mental health conditions among the reasons for CTP use, and the relative dearth of high-quality evidence related to CTP in this context, thereby highlighting the need for further research into the harms and benefits of medical cannabis relative to other therapeutic options. Preliminary evidence suggests that CTP may have potential for the treatment of PTSD, and as a substitute for problematic use of other substances. Extrapolation from reviews of non-therapeutic cannabis use suggests that the use of CTP may be problematic among individuals with psychotic disorders. The clinical implications of CTP use among individuals with mood disorders are unclear. With regard to assessment, evidence suggests that CTP use does not increase risk of harm to self or others. Acute cannabis intoxication and recent CTP use may result in reversible deficits with the potential to influence cognitive assessment, particularly on tests of short-term memory.
Article
Kratom (Mitragyna speciosa) is a plant consumed throughout the world for its stimulant effects and as an opioid substitute (1). It is typically brewed into a tea, chewed, smoked, or ingested in capsules (2). It is also known as Thang, Kakuam, Thom, Ketum, and Biak (3). The Drug Enforcement Administration includes kratom on its Drugs of Concern list (substances that are not currently regulated by the Controlled Substances Act, but that pose risks to persons who abuse them), and the National Institute of Drug Abuse has identified kratom as an emerging drug of abuse (3,4). Published case reports have associated kratom exposure with psychosis, seizures, and deaths (5,6). Because deaths have been attributed to kratom in the United States (7), some jurisdictions have passed or are considering legislation to make kratom use a felony (8). CDC characterized kratom exposures that were reported to poison centers and uploaded to the National Poison Data System (NPDS) during January 2010-December 2015. The NPDS is a national database of information logged by the country's regional poison centers serving all 50 United States, the District of Columbia, and Puerto Rico and is maintained by the American Association of Poison Control Centers. NPDS case records are the result of call reports made by the public and health care providers.
Article
Introduction: The objective of the paper was to highlight the differences in the traditional and non-traditional users of kratom in the South East Asian and Western contexts. Method: A literature survey of published kratom studies among humans was conducted. Forty published studies relevant to the objective were reviewed. Results: Apart from the differences in the sources of supply, patterns of use and social acceptability of kratom within these two regions, the most interesting finding is its evolution to a recreational drug in both settings and the severity of the adverse effects of kratom use reported in the West. While several cases of toxicity and death have emerged in the West, such reports have been non-existent in South East Asia where kratom has had a longer history of use. We highlight the possible reasons for this as discussed in the literature. More importantly, it should be borne in mind that the individual clinical case-reports emerging from the West that link kratom use to adverse reactions or fatalities frequently pertained to kratom used together with other substances. Therefore, there is a danger of these reports being used to strengthen the case for legal sanction against kratom. This would be unfortunate since the experiences from South East Asia suggest considerable potential for therapeutic use among people who use drugs. Conclusion: Despite its addictive properties, reported side-effects and its tendency to be used a recreational drug, more scientific clinical human studies are necessary to determine its potential therapeutic value.
Article
Mu-opioid receptor agonists represent mainstays of pain management. However, the therapeutic use of these agents is associated with serious side effects, including potentially lethal respiratory depression. Accordingly, there is a longstanding interest in the development of new opioid analgesics with improved therapeutic profiles. The alkaloids of the Southeast Asian plant Mitragyna speciosa, represented by the prototypical member mitragynine, are an unusual class of opioid receptor modulators with distinct pharmacological properties. Here we describe the first receptor-level functional characterization of mitragynine and related natural alkaloids at the human mu-, kappa-, and delta-opioid receptors. These results show that mitragynine and the oxidized analogue 7-hydroxymitragynine, are partial agonists of the human mu-opioid receptor and competitive antagonists at the kappa- and delta-opioid receptors. We also show that mitragynine and 7-hydroxymitragynine are G-protein-biased agonists of the mu-opioid receptor, which do not recruit β-arrestin following receptor activation. Therefore, the Mitragyna alkaloid scaffold represents a novel framework for the development of functionally biased opioid modulators, which may exhibit improved therapeutic profiles. Also presented is an enantioselective total synthesis of both (-)-mitragynine and its unnatural enantiomer, (+)-mitragynine, employing a proline-catalyzed Mannich-Michael reaction sequence as the key transformation. Pharmacological evaluation of (+)-mitragynine revealed its much weaker opioid activity. Likewise, the intermediates and chemical transformations developed in the total synthesis allowed the elucidation of previously unexplored structure-activity relationships (SAR) within the Mitragyna scaffold. Molecular docking studies, in combination with the observed chemical SAR, suggest that Mitragyna alkaloids adopt a binding pose at the mu-opioid receptor that is distinct from that of classical opioids.
Article
As a result of the prescription opioid epidemic in the United States, there has been an increasing need for effective treatment interventions, both pharmacological and nonpharmacological. Buprenorphine has emerged as a critical component of the treatment of opioid use disorder, yet its adoption has not been without some concerns. This article first reviews the pharmacology, clinical use, and US legislative action related to buprenorphine, followed by a discussion of the misuse and diversion of buprenorphine in the United States as well as internationally. We then explore the impact of buprenorphine abuse as well as discussing strategies for its reduction, including changes in policy, prescription and pharmacy monitoring, and continuing medical education for guiding and improving clinical practice.
Article
Krathom (Mitragyna speciosa Korth.) is an addictive and illicit substance used in Thailand and other Southeast Asian countries. It has become the most commonly used substance among villagers. The study aimed to explore the factor structure of the krathom withdrawal syndrome based on the findings of an earlier qualitative study. The current study was divided into two stages. Cross-sectional data collections were employed in both phases. The samples comprised, respectively, 196 and 330 krathom users aged over 25 years. The characteristics of krathom withdrawal symptoms and signs were identified and the factor structure examined using exploratory factor analysis (EFA). Confirmatory Factor Analysis (CFA) was used to examine the construct validity and multivariate linear regression was used to identify factors predicting the intensity of krathom withdrawal symptoms. The final scale comprised 20 items with four factors: craving-fatigue syndrome; musculoskeletal system and insomnia; mood symptoms; and autonomic nervous system/physical sickness. Symptoms and signs of krathom withdrawal similar to those of the withdrawal syndrome of opioid substances appear to be present in regular krathom users. The krathom withdrawal intensity is predicted by duration of krathom use, frequency, and daily amount of krathom use.
Article
Importance Opioid analgesic overdose mortality continues to rise in the United States, driven by increases in prescribing for chronic pain. Because chronic pain is a major indication for medical cannabis, laws that establish access to medical cannabis may change overdose mortality related to opioid analgesics in states that have enacted them.Objective To determine the association between the presence of state medical cannabis laws and opioid analgesic overdose mortality.Design, Setting, and Participants A time-series analysis was conducted of medical cannabis laws and state-level death certificate data in the United States from 1999 to 2010; all 50 states were included.Exposures Presence of a law establishing a medical cannabis program in the state.Main Outcomes and Measures Age-adjusted opioid analgesic overdose death rate per 100 000 population in each state. Regression models were developed including state and year fixed effects, the presence of 3 different policies regarding opioid analgesics, and the state-specific unemployment rate.Results Three states (California, Oregon, and Washington) had medical cannabis laws effective prior to 1999. Ten states (Alaska, Colorado, Hawaii, Maine, Michigan, Montana, Nevada, New Mexico, Rhode Island, and Vermont) enacted medical cannabis laws between 1999 and 2010. States with medical cannabis laws had a 24.8% lower mean annual opioid overdose mortality rate (95% CI, −37.5% to −9.5%; P = .003) compared with states without medical cannabis laws. Examination of the association between medical cannabis laws and opioid analgesic overdose mortality in each year after implementation of the law showed that such laws were associated with a lower rate of overdose mortality that generally strengthened over time: year 1 (−19.9%; 95% CI, −30.6% to −7.7%; P = .002), year 2 (−25.2%; 95% CI, −40.6% to −5.9%; P = .01), year 3 (−23.6%; 95% CI, −41.1% to −1.0%; P = .04), year 4 (−20.2%; 95% CI, −33.6% to −4.0%; P = .02), year 5 (−33.7%; 95% CI, −50.9% to −10.4%; P = .008), and year 6 (−33.3%; 95% CI, −44.7% to −19.6%; P < .001). In secondary analyses, the findings remained similar.Conclusions and Relevance Medical cannabis laws are associated with significantly lower state-level opioid overdose mortality rates. Further investigation is required to determine how medical cannabis laws may interact with policies aimed at preventing opioid analgesic overdose.
Article
Kratom (Mitragyna speciosa Korth), a native tree in Southeast Asia, is misused as an abuse drug and becomes legally widespread to several countries. Currently, it is available through the online market or by some shops. The clinical manifestations of Kratom's effects are not well-defined and the clinical studies are limited. This study was designed to identify the characteristics of Kratom poisoning and withdrawal cases from Kratom exposure cases in Ramathibodi Poison Center (RPC), Thailand, during a five-year period. We used a retrospective review of Kratom exposure cases from the RPC toxic surveillance system. A total of 52 Kratom exposure cases were identified. The trend of case consultations has been increasing. There were Kratom poisoning cases (76.9%) and withdrawal cases (23.1%). Common presenting symptoms in the poisoning group were palpitation (22.5%), followed by seizure (17.5%). For the withdrawal group, the common presenting symptoms were myalgia (33.3%), insomnia (16.67%), fatigue (16.67%), and chest discomfort (16.67%). There was a baby with withdrawal symptoms who was delivered from a chronic Kratom-abusing mother, suggesting possible exposure via the transplacental route. There were no deaths in either group. Kratom abuse can cause either poisoning or withdrawal. Most cases in both groups had good prognostic outcome.
Article
Kratom use is a growing problem in the United States. Kratom exposures reported to Texas poison centers between January 1998 and September 2013 were identified. No kratom exposures were reported from 1998 to 2008 and 14 exposures were reported from 2009 to September 2013. Eleven patients were male, and 11 patients were in their 20s. The kratom was ingested in 12 patients, inhaled in 1, and both ingested and inhaled in 1. Twelve patients were managed at a healthcare facility and the remaining 2 were managed at home.
Article
Background: Krathom is currently the most popular illicit substance in use in southern Thailand. Research regarding its effects and health impacts is scarce. This study explored the pattern of krathom use and users' perceptions of the consequences of its use. Methods: An in-depth qualitative interview. A group of 34 self-identified regular users, occasional users, non-users and ex-users of krathom was used in this study. Health volunteer as a key-contact person helped the researcher to invite villagers to participate in the study using snowballing technique. The process of data analysis was guided by Strauss and Corbin's grounded theory. Results: The core category, 'Understanding krathom use', was generated from three inter-related categories: (i) reasons for continuing krathom use, (ii) the way of applying krathom, and (iii) perceiving positive and realizing the negative effects of krathom use and their 18 subcategories. Conclusions: The study findings reveal the importance of considering krathom use from the perspective and belief of the villagers. Krathom is addictive with its own characteristic symptoms and signs. The results provide support for policy interventions to control the availability of krathom according to the community context. In addition, krathom misuse by adolescents must be considered.
Article
A 17-year-old white man who showed no obvious signs of trauma was found unresponsive in bed and was pronounced dead at the scene. The decedent had a documented history of heroin abuse and chronic back pain and reportedly self-medicated with Kratom (mitragynine). The autopsy was remarkable only for pulmonary congestion and edema and a distended bladder, both of which are consistent with, though not diagnostic of, opiate use. A laboratory work-up revealed therapeutic levels of over-the-counter cold medications and benzodiazepines. However, of interest was a level of mitragynine at 0.60 mg/L. Given the facts of the case, the Medical Examiner certified the cause of death as "possible Kratom toxicity" and the manner of death was classified as "accident."