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  1. Singh D, Narayanan S, Grundmann O, Dzulkapli EB, Vicknasingam B
    Subst Use Misuse, 2019;54(14):2284-2289.
    PMID: 31347441 DOI: 10.1080/10826084.2019.1645178
    Background: Mitragyna speciosa (Korth.) or kratom is an indigenous medicinal plant of Southeast Asia. Kratom is widely reported to have dose-dependent effects based on available literature, but to our knowledge, this has not been established conclusively. Objective: This study sought to evaluate if kratom use produces dose-dependent effects, with a stimulant effect at low doses and a sedative effect at high doses, in a sample of regular kratom users. Methods: A total of 63 regular kratom users participated in this cross-sectional study. The Brief-Biphasic Alcohol Effects Scale (B-BAES) was used to determine subjects self-report kratom use experiences. Results: Almost all in the sample were male (98%, n = 62/63), and the majority of subjects were Malays (94%, n = 59/63). The mean age of the subjects in the sample was 43.8 years (SD = 12.1). Seventy-five percent (n = 47/63) have >5 years kratom use history, and 65% (n = 41/63) consumed >3 glasses of kratom daily. Results from first test showed no significant difference in the stimulant (t61 =0.371, p 3 glasses a day or less than this amount, regardless of duration of use. In the second test, no significant differences in the mean scores were found among those who consumed >3 glasses daily or less than this amount among short-term or long-term uses. Conclusions: Daily kratom use produced both stimulant and sedative effects but they were not statistically significantly associated with the dose consumed, both among short-term and long-term users in our sample.
  2. Singh D, Narayanan S, Grundmann O, Boyer EW, Vicknasingam B
    J Psychoactive Drugs, 2019 06 20;52(1):86-92.
    PMID: 31218929 DOI: 10.1080/02791072.2019.1632505
    The leaves from Mitragyna speciosa (Korth.) trees, also known as kratom, are traditionally used in Southeast Asia as a mild psychotropic agent. We investigated the demographic characteristics of persons who used both kratom cocktail and benzodiazepines (BZO) in a sample drawn from a rural area in Penang, Malaysia, and the reasons for BZO use. Seventy-seven participants who currently use a kratom cocktail along with BZO were recruited through snowball sampling for this cross-sectional study. The participants were male, and the majority were Malays (99%, n = 76/77), single (57%, n = 44/77) and employed (91%, n = 70/77). BZO was used with kratom cocktail 1) to increase euphoria; 2) to reduce dependence on methamphetamine; 3) to promote sleep; 4) to ease methamphetamine-associated psychological symptoms and 5) to decrease the craving for kratom. There were no significant differences in the intake of kratom use (p = .751), BZO use duration (p = .259), frequency (p = .188) and quantity (p = .888) of BZO use in the last 7 days, and quantity of BZO use in the last 30 days (p = .337) between kratom users and kratom poly-drug users. An awareness of the health consequences of the co-use of kratom with BZO is needed to prevent untoward health incidents.
  3. Singh, Darshan, Chye, Yann, Chao, Suo, Yücel, Murat, Grundmann, Oliver, Muhamad Zabidi Ahmad, et al.
    MyJurnal
    Mitragyna speciosa (Korth.) or kratom is a native medicinal plant of Southeast Asia. Commonly used by hard labours in harsh working environment, the ingestion of brewed kratom decoction is reported to produce dose-dependent stimulant and opioid-like effects. Kratom is also regularly consumed as a pain killer and as traditional cure for common maladies such as fever and cough. However, it remains unknown whether regular consumption of kratom decoction is associated with brain abnormalities in regular users in traditional settings. Methods: A total of 14 subjects (7 regular kratom users and 7 non-kratom users) voluntarily participated in this cross-sectional study. Face-to-face interviews were conducted with kratom users to determine history of kratom use and later these respondents underwent brain magnetic resonance imaging (MRI). Results: There were no significant differences (p>0.05) in the intracranial volume (ICV), cortical volumes (frontal, parietal, temporal, occipital, or cingulate lobe), or subcortical volumes (striatum, hippocampus, or amygdala), as well as in the diffusion tensor imaging (DTI) metrics, fractional anisotropy (FA) and mean diffusivity (MD) between kratom users and the controls. Conclusion: This preliminary study showed long-term consumption of kratom decoction is not significantly associated with altered brain structures in regular kratom users in traditional settings. However, further study is needed to establish more data for kratom use and its effects.
  4. Metastasio A, Prevete E, Singh D, Grundmann O, Prozialeck WC, Veltri C, et al.
    Front Psychiatry, 2020;11:594816.
    PMID: 33329145 DOI: 10.3389/fpsyt.2020.594816
    Among the symptoms of COVID-19 fever, general malaise, pain and aches, myalgia, fatigue, and headache can affect the quality of life of patients, even after the end of the acute phase of the infection and can be long lasting. The current treatment of these symptoms, also because COVID-19 patients have been asked not to use non-steroidal anti-inflammatory drugs (NSAIDs), in particular ibuprofen are often unsatisfactory. Among the above mentioned symptoms malaise and fatigue seem the most difficult to treat. In this case report we describe the use of kratom (Mitragyna speciosa) by a patient with confirmed COVID-19 infection. What we observed was a fast and sustained relieve of the above mentioned symptoms.
  5. Bath R, Bucholz T, Buros AF, Singh D, Smith KE, Veltri CA, et al.
    J Addict Med, 2019 10 1;14(3):244-252.
    PMID: 31567595 DOI: 10.1097/ADM.0000000000000570
    OBJECTIVES: To determine whether diagnosed pre-existing health conditions correlate with Kratom demographics and use patterns.

    METHODS: A cross-sectional, anonymous US national online survey was conducted among 8049 Kratom users in October, 2016 to obtain demographic, health, and Kratom use pattern information.

    RESULTS: People who use Kratom to mitigate illicit drug dependence self-reported less pain and better overall health than individuals who used Kratom for acute/chronic pain. Self-reported improvements in pre-existing mental health symptoms (attention deficit and hyperactivity disorder/attention deficit disorder, anxiety, bipolar disorder, post-traumatic stress disorder, and depression) attributed to Kratom use were greater than those related to somatic symptoms (back pain, rheumatoid arthritis, acute pain, chronic pain, fibromyalgia). Demographic variables, including female sex, older age, employment status, and insurance coverage correlated with increased likelihood of Kratom use.

    CONCLUSIONS: Kratom use may serve as a self-treatment strategy for a diverse population of patients with pre-existing health diagnoses. Healthcare providers need to be engaging with patients to address safety concerns and potential limitations of its use in clinical practice for specific health conditions.

  6. Singh D, Narayanan S, Vicknasingam B, Prozialeck WC, Smith KE, Corazza O, et al.
    J Addict Med, 2021 5 19;16(2):223-228.
    PMID: 34001777 DOI: 10.1097/ADM.0000000000000876
    OBJECTIVES: Kratom (Mitragyna speciosa Korth.), an indigenous medicinal plant, has been widely used as a traditional remedy in Southeast Asia. However, its combined consumption with other substances has received scarce attention. This study investigates the use of kratom among adults with a history of using heroin and methamphetamine in Malaysia.

    METHODS: A total of 332 patients who were mandated to undergo drug rehabilitation participated in this cross-sectional study. The study data were collected through face-to-face interviews using a semi-structured questionnaire.

    RESULTS: The majority were males (95%, n = 314/332) and Malays (98%, n = 325/332) with a mean age of 32.3 years (SD = 9.16). Over two thirds of the respondents used kratom to alleviate heroin withdrawal symptoms and to reduce methamphetamine intake; 59% used it as a substitute for heroin and methamphetamine. A similar proportion used kratom to reduce heroin intake (58%), while only 15% used it for its euphoric effects. Multivariate analysis showed that previous attendees of government rehabilitation programs had lower odds of using kratom as a heroin substitute.

    CONCLUSIONS: The potential of kratom to alleviate heroin withdrawal symptoms, and to reduce methamphetamine and heroin intake, among people who co-use heroin and methamphetamine warrants further research.

  7. Saref A, Suraya S, Singh D, Grundmann O, Narayanan S, Swogger MT, et al.
    J Ethnopharmacol, 2019 Jun 28;238:111876.
    PMID: 31014959 DOI: 10.1016/j.jep.2019.111876
    ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa (Korth.) is a traditional medicinal plant widely used in Southeast Asia for its opioid-like effects. Although kratom produces analgesia through binding of mitragynine and other alkaloids at the mu-opioid receptor (MOR), the association of long-term kratom use with adverse opioid-like effects remains unknown.

    AIM OF THE STUDY: To determine the self-reported prevalence and severity of opioid-related adverse effects after kratom initiation in a cohort of illicit opioid users.

    MATERIALS AND METHODS: A total of 163 illicit opioid users with current kratom use history were recruited through convenience sampling from the northern states of Peninsular Malaysia. Face-to-face interviews were conducted using a semi-structured questionnaire.

    RESULTS: Respondents were all males, majority Malays (94%, n = 154/163), with a mean age of 37.10 years (SD = 10.9). Most were single (65%, n = 106/163), had 11 years of education (52%, n = 85/163) and employed (88%, n = 144/163). Half reported using kratom for over >6 years (50%, n = 81/163), and 41% consumed >3 glasses of kratom daily (n = 67/163). Results from Chi-square analysis showed kratom initiation was associated with decreased prevalence of respiratory depression, constipation, physical pain, insomnia, depression, loss of appetite, craving, decreased sexual performance, weight loss and fatigue.

    CONCLUSIONS: Our findings indicate that kratom initiation (approximately 214.29 mg of mitragynine) was associated with significant decreases in the prevalence and severity of opioid adverse effects.

  8. Grundmann O, Babin JK, Henningfield JE, Garcia-Romeu A, Kruegel AC, Prozialeck WC, et al.
    Addiction, 2021 01;116(1):202-203.
    PMID: 32602213 DOI: 10.1111/add.15173
  9. Saref A, Suraya S, Singh D, Grundmann O, Narayanan S, Swogger MT, et al.
    J Psychoactive Drugs, 2019 11 04;52(2):138-144.
    PMID: 31682782 DOI: 10.1080/02791072.2019.1686553
    This study sought to determine the relationship between kratom (Mitragyna speciosa) initiation and regular consumption of illicit drugs and HIV risk behaviors in a cohort of illicit drug users in Malaysia. 260 illicit drug users with current kratom use were recruited through convenience sampling for this cross-sectional study. All were male, with the majority being Malays (95%, n = 246/260). Results suggest that kratom initiation was associated with significant decrease in the regular use of heroin (odds ratio (OR) = 0.50, 95% confidence interval (CI): 0.40- 0.72; p = .0001), methamphetamine (OR = 0.23, CI: 0.16- 0.35; p < .0001), and amphetamine (OR = 0.17, CI: 0.09- 0.34; p < .0001). Kratom initiation was also associated with reduction in regular HIV risk behaviors such as having sex with sex workers (OR = 0.20, CI: 0.12-0.32; p < .0001), using drugs before sexual intercourse (OR = 0.20, CI: 0.13- 0.31; p < .0001), injecting behaviors (OR = 0.10, CI: 0.04- 0.25; p < .0001), sharing of injection equipment (OR = 0.13, CI: 0.04- 0.43; p < .0001), and injecting with other injection drug users (IDUs) (OR = 0.07, CI: 0.02- 0.24; p < .0001).
  10. Singh D, Narayanan S, Suraya S, Saref A, Grundmann O, Prozialeck WC, et al.
    J Psychoactive Drugs, 2020 03 10;52(3):282-288.
    PMID: 32153252 DOI: 10.1080/02791072.2020.1738603
    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
  11. Leong Abdullah MFI, Tan KL, Narayanan S, Yuvashnee N, Chear NJY, Singh D, et al.
    Clin Toxicol (Phila), 2021 May;59(5):400-408.
    PMID: 32870119 DOI: 10.1080/15563650.2020.1812627
    OBJECTIVES: Little is known about the cardiotoxic effects of kratom (Mitragyna speciosa Korth.), a medicinal plant. This analytical cross-sectional study investigated the prevalence of electrocardiogram (ECG) abnormalities and QTc intervals in regular kratom users compared with non-kratom-using control subjects.

    METHODS: We enrolled regular kratom users and non-kratom-using control subjects from three communities. Demographic data, clinical data, kratom use characteristics, and ECG findings were recorded. The mitragynine content of kratom juice was quantified using a validated gas chromatography-mass spectrometry (GC-MS) method.

    RESULTS: A total of 200 participants (100 kratom users and 100 control subjects) participated in this study. The prevalence of ECG abnormalities in kratom users (28%) did not differ from that of control subjects (32%). Kratom use was not associated with ECG abnormalities, except for significantly higher odds of sinus tachycardia (OR = 8.61, 95% CI = 1.06-70.17, p = 0.035) among kratom users compared with control subjects. The odds of observing borderline QTc intervals were significantly higher for kratom users compared with control subjects, regardless of the age of first use, the duration of use, the daily quantity consumed, and the length of time that had elapsed between last kratom use and ECG assessment. Nevertheless, there were no differences in the odds of having prolonged QTc intervals between kratom users and controls. The estimated average daily intake of mitragynine consumed by kratom users was 434.28 mg.

    CONCLUSION: We found no link between regular kratom use and electrocardiographic abnormalities with an estimated average daily intake of 434.28 mg of mitragynine.

  12. Singh D, Murugaiyah V, Hamid SBS, Kasinather V, Chan MSA, Ho ETW, et al.
    J Ethnopharmacol, 2018 Jul 15;221:30-36.
    PMID: 29626673 DOI: 10.1016/j.jep.2018.04.005
    ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa (Korth.) also known as kratom, is a native medicinal plant of Southeast Asia with opioid-like effects. Kratom tea/juice have been traditionally used as a folk remedy and for controlling opiate withdrawal in Malaysia. Long-term opioid use is associated with depletion in testosterone levels.

    AIM OF THE STUDY: Since kratom is reported to deform sperm morphology and reduce sperm motility, we aimed to clinically investigate the testosterone levels following long-term kratom tea/juice use in regular kratom users.

    METHODS: A total of 19 regular kratom users were recruited for this cross-sectional study. A full-blood test was conducted including determination of testosterone level, follicle stimulating hormone (FSH) and luteinizing hormone (LH) profile, as well as hematological and biochemical parameters of participants.

    RESULTS: We found long-term kratom tea/juice consumption with a daily mitragynine dose of 76.23-94.15 mg did not impair testosterone levels, or gonadotrophins, hematological and biochemical parameters in regular kratom users.

    CONCLUSION: Regular kratom tea/juice consumption over prolonged periods (>2 years) was not associated with testosterone impairing effects in humans.

  13. Grundmann O, Veltri CA, Morcos D, Knightes D, Smith KE, Singh D, et al.
    Am J Drug Alcohol Abuse, 2022 Jul 04;48(4):433-444.
    PMID: 35389321 DOI: 10.1080/00952990.2022.2041026
    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.
  14. Grundmann O, Veltri CA, Morcos S, Smith KE, Singh D, Corazza O, et al.
    Exp Clin Psychopharmacol, 2023 Oct;31(5):963-977.
    PMID: 36634016 DOI: 10.1037/pha0000632
    Kratom (Mitragyna speciosa Korth.) use has increased substantially over the past decade outside of its indigenous regions, especially for the self-treatment of psychiatric conditions. An anonymous, cross-sectional, online survey was completed by 4,945 people who use kratom (PWUK) between July 2019 and July 2020. A total of 2,296 respondents completed an extended survey that included clinical scales for measuring attention deficit hyperactivity disorder (ADHD), posttraumatic stress disorder (PTSD), depressive and anxiety disorders. PWUK and met criteria for ADHD, PTSD, depressive or anxiety disorders were primarily middle-aged (31-50 years), employed, college-level educated, and reported greater concurrent or prior use of kratom with cannabis, cannabidiol, and benzodiazepines. For all psychiatric conditions, PWUK reported decreased depressive and anxious moods than before kratom use. Based on this self-report study, observational and other clinical studies are warranted for kratom. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
  15. Prozialeck WC, Avery BA, Boyer EW, Grundmann O, Henningfield JE, Kruegel AC, et al.
    Int J Drug Policy, 2019 08;70:70-77.
    PMID: 31103778 DOI: 10.1016/j.drugpo.2019.05.003
    Kratom (Mitragyna speciosa) is a tree-like plant indigenous to Southeast Asia. Its leaves, and the teas brewed from them have long been used by people in that region to stave off fatigue and to manage pain and opioid withdrawal. Evidence suggests kratom is being increasingly used by people in the United States and Europe for the self-management of opioid withdrawal and treatment of pain. Recent studies have confirmed that kratom and its chemical constituents have potentially useful pharmacological actions. However, there have also been increasing numbers of reports of adverse effects resulting from use of kratom products. In August 2016, the US Drug Enforcement Administration announced plans to classify kratom and its mitragynine constituents as Schedule I Controlled Substances, a move that triggered a massive response from pro-kratom advocates. The debate regarding the risks, and benefits and safety of kratom continues to intensify. Kratom proponents tout kratom as a safer and less addictive alternative to opioids for the management of pain and opioid addiction. The anti-kratom faction argues that kratom, itself, is a dangerous and addictive drug that ought to be banned. Given the widespread use of kratom and the extensive media attention it is receiving, it is important for physicians, scientists and policy makers to be knowledgeable about the subject. The purpose of this commentary is to update readers about recent developments and controversies in this rapidly evolving area. All of the authors are engaged in various aspects of kratom research and it is our intention to provide a fair and balanced overview that can form the basis for informed decisions on kratom policy. Our conclusions from these analyses are: (a) User reports and results of preclinical studies in animals strongly suggest that kratom and its main constituent alkaloid, mitragynine may have useful activity in alleviating pain and managing symptoms of opioid withdrawal, even though well-controlled clinical trials have yet to be done. (b) Even though kratom lacks many of the toxicities of classic opioids, there are legitimate concerns about the safety and lack of quality control of purported "kratom" products that are being sold in the US. (c) The issues regarding the safety and efficacy of kratom and its mitragynine constituent can only be resolved by additional research. Classification of the Mitragyna alkaloids as Schedule I controlled substances would substantially impede this important research on kratom.
  16. Singh D, Brown PN, Cinosi E, Corazza O, Henningfield JE, Garcia-Romeu A, et al.
    Front Psychiatry, 2020;11:574483.
    PMID: 33324252 DOI: 10.3389/fpsyt.2020.574483
    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.
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