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Bowe A, Kerr PL. Endogenous Opioid Activity as the Mechanism of Action for Mitragyna speciosa (Kratom): The Current State of the Evidence. ADVANCES IN NEUROBIOLOGY 2024; 35:287-313. [PMID: 38874729 DOI: 10.1007/978-3-031-45493-6_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2024]
Abstract
Kratom (Mitragyna speciosa) is a substance derived from botanical compounds native to Southeast Asia. This substance has been cultivated predominantly in Thailand, Malaysia, Vietnam, and Myanmar, where it has historically been used in traditional medicine as a near panacea for several health problems. Such ritualistic use of kratom has been present for centuries; however, recreational use appears to have increased globally, especially in the United States. Pharmacodynamic and pharmacokinetic studies have found that kratom demonstrates a unique parabolic, dose-dependent pattern of effects ranging from stimulation to opioid and analgesic effects. Pharmacological research indicates that kratom is both a mu opioid receptor (μ-OR; MOR) and a kappa opioid receptor (κ-OR; KOR) agonist, which mediates its analgesic effects. Other research suggests that kratom may simultaneously act on dopaminergic and serotonergic receptors, which mediate its stimulant effects. This chapter reviews the literature related to the structural, functional, and cultural characteristics of kratom use. We begin with an overview of current and historical patterns of kratom, followed by a review of data on the pharmacodynamics and pharmacokinetics of kratom thus far.
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MESH Headings
- Mitragyna
- Humans
- Plant Extracts/pharmacology
- Animals
- Receptors, Opioid, kappa/metabolism
- Receptors, Opioid, kappa/agonists
- Analgesics, Opioid/pharmacology
- Analgesics, Opioid/therapeutic use
- Receptors, Opioid, mu/metabolism
- Receptors, Opioid, mu/agonists
- Asia, Southeastern
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Affiliation(s)
- Adina Bowe
- West Virginia University School of Medicine-Charleston, Charleston, WV, USA.
| | - Patrick L Kerr
- West Virginia University School of Medicine-Charleston, Charleston, WV, USA
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LoParco CR, Yockey RA, Sekhon VK, Olsson S, Galindo R, Balasundaram R, Agwuncha T, Rossheim ME. Kratom Retail Availability in Fort Worth, Texas. J Psychoactive Drugs 2024; 56:8-13. [PMID: 36841785 DOI: 10.1080/02791072.2023.2181243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 12/12/2022] [Accepted: 12/14/2022] [Indexed: 02/27/2023]
Abstract
Kratom use is associated with cannabis use, so retail availability may also be related. Kratom and Delta-8 THC (a psychoactive cannabis product) are federally unregulated, marketed as "natural," and often used for pain relief and/or relaxation. Kratom may have greater retail availability in more socioeconomically deprived areas because harmful substances are frequently marketed to lower-income communities. This study examined kratom retail availability in Fort Worth, Texas. Locations with alcohol, tobacco, and/or CBD licenses were called in July 2022: 1,025/1,223 (84%) answered the phone. T-tests examined potential differences in socioeconomic deprivation scores surrounding outlets by whether they sold kratom. Cross-tabulations examined overlap in kratom and Delta-8 THC availability. Kratom was available in 6% of locations. Most kratom retailers had a tobacco license (92%). However, most stores with a tobacco license did not sell kratom (14%), whereas most stores with a CBD license did (55%). Kratom availability was not associated with area deprivation scores. Most kratom retailers (95%) sold Delta-8 THC and two-thirds (65%) of Delta-8 THC retailers sold kratom. This study was the first to examine retail availability of kratom. Findings indicate the presence of niche stores specializing in the retail of federally unregulated substances.
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Affiliation(s)
- C R LoParco
- School of Public Health, University of North Texas Health Science Center, Fort Worth, TX, USA
| | - R A Yockey
- School of Public Health, University of North Texas Health Science Center, Fort Worth, TX, USA
| | - V K Sekhon
- Department of Analytics, Harrisburg University of Science and Technology, Harrisburg, PA, USA
| | - S Olsson
- School of Medicine, Texas Christian University, Fort Worth, TX, USA
| | - R Galindo
- School of Public Health, University of North Texas Health Science Center, Fort Worth, TX, USA
| | - R Balasundaram
- School of Public Health, University of North Texas Health Science Center, Fort Worth, TX, USA
| | - T Agwuncha
- School of Public Health, University of North Texas Health Science Center, Fort Worth, TX, USA
| | - M E Rossheim
- School of Public Health, University of North Texas Health Science Center, Fort Worth, TX, USA
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Kiyokawa M, Kwon AK, Cape MC, Streltzer JM. Kratom use disorder: case reports on successful treatment with home induction of buprenorphine-naloxone. Fam Pract 2023; 40:596-598. [PMID: 37499179 DOI: 10.1093/fampra/cmad081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/29/2023] Open
Abstract
BACKGROUND Kratom has been used for different reasons such as pain, opioid withdrawal, and relaxation. Kratom can cause dependence and overdose, and it's classified under 'drugs of concern' by the US Drug Enforcement Administration. Despite these concerns, kratom is legal in most of the United States and many countries around the world with easy accessibility. Literature searches reveal recommendations to use buprenorphine (or buprenorphine-naloxone), which are medications to treat opioid use disorder, in order to treat patients with kratom use disorder; however, there are no formal guidelines available. Buprenorphine (or buprenorphine-naloxone) induction is recommended to be conducted under observation (i.e. in the clinic) in the United States, but COVID-19 has resulted in shifts toward telehealth. OBJECTIVES Describe case series of successful management of kratom use disorder using telehealth followed by unobserved buprenorphine-naloxone home induction and highlight implications for future management, including maintenance dosage and induction method. METHODS We present 2 very similar kratom use disorder patients who reported taking 35 g of kratom per day who underwent unobserved buprenorphine-naloxone home induction. RESULTS Both were seen via telehealth initially. They reported no adverse effects before, during, or after the unobserved home induction on buprenorphine-naloxone but stabilized on significantly different dosages. CONCLUSION Telehealth followed by unobserved buprenorphine-naloxone induction at home may be an alternative to traditional buprenorphine-naloxone induction where treatment accessibility is limited. In addition to daily doses of kratom use, other factors, such as duration of kratom use and individual psychological factors may determine the most comfortable dose of buprenorphine-naloxone.
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Affiliation(s)
- Miki Kiyokawa
- Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, United States
- Department of Psychiatry, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, United States
| | - Anthony K Kwon
- Department of Family Medicine and Community Health, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, United States
| | - Micaiah C Cape
- Department of Psychiatry, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, United States
| | - Jon M Streltzer
- Department of Psychiatry, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, United States
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Bowman J, Lai M, Charles JE, Gordon AJ, Smid MC. Kratom Use Among Pregnant and Lactating Individuals With Substance Use Disorder. J Addict Med 2023; 17:722-724. [PMID: 37934544 DOI: 10.1097/adm.0000000000001212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/25/2023]
Abstract
OBJECTIVE Kratom ( Mitragyna speciosa ) use in pregnancy is associated with maternal and neonatal opioid withdrawal syndrome. However, kratom use patterns in the population of peripartum and postpartum individuals with substance use disorder (SUD) are unknown. The aim of this study was to determine the proportion of pregnant and postpartum individuals with SUD who report using kratom in pregnancy or lactation and the reasons for their use. METHODS We conducted an anonymous survey of pregnant and postpartum individuals receiving care at a single center's multidisciplinary prenatal clinic for individuals with SUD. We collected participants' demographic and pregnancy characteristics. We assessed ever use of kratom, kratom use during pregnancy or lactation, and reasons for kratom use. Descriptive statistics were used to summarize the data. RESULTS From January 2021 to May 2021, a total of 80 surveys were collected (81% response rate of 98 eligible individuals). Most respondents were pregnant (n = 50 [62.5%]). The most frequent substance(s) of use were opioids (n = 50 [62.5%]) and methamphetamine (n = 39 [48.8%]). Many (n = 26 [32.5%]) reported ever use of kratom use. Of all respondents, 4 (5%) reported use during pregnancy, and 1 (1%) reported use during lactation. Kratom was primarily used to relieve opioid withdrawal symptoms and for relaxation, pain control, and stress relief. CONCLUSION In a survey of pregnant and postpartum individuals with SUD at a single high-risk pregnancy clinic, ever use of kratom was frequent, whereas peripartum use was rare.
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Affiliation(s)
- Justin Bowman
- From the University of Utah School of Medicine, Salt Lake City, UT (JB); Department of Obstetrics and Gynecology, Division of Maternal and Fetal Medicine, University of Utah Health, Salt Lake City, UT (JEC, MCS); Department of Pharmacotherapy, University of Utah College of Pharmacy, Salt Lake City, UT (ML, AJG); Program for Addiction Research, Clinical Care, Knowledge and Advocacy, Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT (JEC, MCS); and Informatics, Decision-Enhancement, and Analytic Sciences Center, Salt Lake City VA Health Care System, Salt Lake City, UT (AJG)
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Grundmann O, Hendrickson RG, Greenberg MI. Kratom: History, pharmacology, current user trends, adverse health effects and potential benefits. Dis Mon 2023; 69:101442. [PMID: 35732553 DOI: 10.1016/j.disamonth.2022.101442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Kratom (Mitragyna speciosa Korth.) is a tree native to Southeast Asia with dose-dependent stimulant and opioid-like effects. Dried, powdered leaf material is among the kratom products most commonly consumed in the US and Europe, but other formulations also exist including enriched extracts, resins, tinctures, and edibles. Its prevalence in the US remains debated and the use pattern includes self-treatment of mood disorders, pain, and substance use disorders. Most of the adverse effects of kratom and its alkaloid mitragynine have been reported in the literature as case reports or part of surveys necessitating confirmation by clinical trials. Toxicities associated with kratom consumption have focused on hepatic, cardiac, and CNS effects with the potential to cause fatalities primarily as part of polydrug exposures. Kratom may also present with drug-drug interactions primarily through CYP 3A4 and 2D6 inhibition, although the clinical significance remains unknown to date. The variability in composition of commercially available kratom products complicates generalization of findings and requires further investigation by employing clinical trials. Healthcare professionals should remain cautious in counseling patients on the use of kratom in a therapeutic setting.
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Affiliation(s)
- Oliver Grundmann
- Department of Medicinal Chemistry, College of Pharmacy, University of Florida, 1345 Center Drive, Room P3-20, Gainesville, FL 32611, United States.
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Prevete E, Kuypers KPC, Theunissen EL, Esposito G, Ramaekers JG, Pasquini M, Corazza O. Clinical Implications of Kratom ( Mitragyna speciosa) Use: a Literature Review. CURRENT ADDICTION REPORTS 2023; 10:317-334. [PMID: 37266188 PMCID: PMC10177737 DOI: 10.1007/s40429-023-00478-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/30/2023] [Indexed: 06/03/2023]
Abstract
PURPOSE OF REVIEW This work aims to provide an up-to-date review of the preclinical and clinical scientific literature on the therapeutic value of kratom to better understand the underlying mechanisms related to its use and inform future therapeutic applications. RECENT FINDINGS A growing number of studies, mainly of cross-sectional nature, describe the widespread use of kratom by individuals to self-treat pain, psychiatric symptoms, and substance use disorders (SUD) outside a controlled clinical setting. Preclinical evidence suggests kratom is effective as an analgesic agent and might decrease the self-administration of other drugs. A randomized controlled trial has further supported kratom's therapeutic value as an analgesic. Investigations in nonclinical samples of long-term kratom users also indicate its therapeutic benefit in managing SUD symptoms (e.g., craving) and long-term or acute symptoms (e.g., withdrawal) for alcohol, opioids, and other illicit drugs. However, episodes of kratom-related intoxications have also been reported, often due to the adulteration and the contamination of kratom products mainly sold online or mixed toxicities when consumed outside clinical and traditional settings. SUMMARY Evidence on the clinical implications of kratom use is still limited and uncertain, with kratom research constantly evolving. Therefore, further randomized trials are needed.
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Affiliation(s)
- Elisabeth Prevete
- Department of Human Neurosciences, Sapienza University of Rome, Viale Dell’Università 30, 00185 Rome, Italy
- Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands
| | - Kim Paula Colette Kuypers
- Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands
| | - Eef Lien Theunissen
- Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands
| | - Gianluca Esposito
- Department of Psychology and Cognitive Science, University of Trento, Corso Bettini, 84, 38068 Rovereto, Italy
| | - Johannes Gerardus Ramaekers
- Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands
| | - Massimo Pasquini
- Department of Human Neurosciences, Sapienza University of Rome, Viale Dell’Università 30, 00185 Rome, Italy
| | - Ornella Corazza
- Department of Psychology and Cognitive Science, University of Trento, Corso Bettini, 84, 38068 Rovereto, Italy
- Department of Clinical, Pharmacological and Biological Sciences, University of Hertfordshire, College Lane, Hatfield, AL10 9AB UK
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Mukhopadhyay S, Gupta S, Wilkerson JL, Sharma A, McMahon LR, McCurdy CR. Receptor Selectivity and Therapeutic Potential of Kratom in Substance Use Disorders. CURRENT ADDICTION REPORTS 2023. [DOI: 10.1007/s40429-023-00472-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/31/2023]
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Hughs M, Kish-Trier E, O'Brien A, McMillin GA. Analysis of Mitragynine and Speciociliatine in Umbilical Cord by LC-MS-MS for Detecting Prenatal Exposure to Kratom. J Anal Toxicol 2023; 46:957-964. [PMID: 36047661 DOI: 10.1093/jat/bkac064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 08/22/2022] [Accepted: 08/30/2022] [Indexed: 01/26/2023] Open
Abstract
Kratom is an herbal drug that is legal in the USA. While it is marketed as a safer alternative to opioids, it can cause opioid-like withdrawal symptoms when discontinued after regular use. Several case studies have shown that kratom exposure in utero can lead to symptoms in newborns consistent with neonatal abstinence syndrome. Here, we present a validated method for the detection of kratom in umbilical cord by liquid chromatography--tandem mass spectrometry. The umbilical cord is homogenized in solvent and kratom analytes are purified by solid phase extraction (strong cation exchange). Diastereomeric kratom alkaloids mitragynine (MG), speciociliatine (SC), speciogynine and mitraciliatine are separated by reverse phase chromatography on a phenyl-hexyl column. Applying this method to residual umbilical cords submitted to our laboratory for drug testing, 29 positive specimens exhibiting varied kratom analyte distributions were observed. MG and SC were the most abundant kratom analytes and were selected as biomarkers of kratom exposure. A cutoff concentration of 0.08 ng/g was established for both MG and SC.
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Affiliation(s)
- Melissa Hughs
- ARUP Institute for Clinical and Experimental Pathology, 500 Chipeta Way, Salt Lake City, UT 84108, USA
| | - Erik Kish-Trier
- ARUP Institute for Clinical and Experimental Pathology, 500 Chipeta Way, Salt Lake City, UT 84108, USA
| | - Aidin O'Brien
- ARUP Institute for Clinical and Experimental Pathology, 500 Chipeta Way, Salt Lake City, UT 84108, USA
| | - Gwendolyn A McMillin
- ARUP Institute for Clinical and Experimental Pathology, 500 Chipeta Way, Salt Lake City, UT 84108, USA.,Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive, East Street #1100, Salt Lake City, UT 84112, USA
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Basheer M, Khudhair Jasim R, Harn GL. Controversial usages of kratom ( Mitragyna speciosa): For good or for evil. World J Pharmacol 2022; 11:16-26. [DOI: 10.5497/wjp.v11.i3.16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 10/04/2022] [Accepted: 11/23/2022] [Indexed: 11/28/2022] Open
Abstract
Kratom (Mitragyna speciosa) is a plant that grows well in tropical climates such as in Southeast Asia. Traditionally, people discovered it possessed a stimulating effect that relieved tiredness. Furthermore, it contains analgesic and medicinal properties for the treatment of pain, diarrhea, muscle discomfort, and blood pressure and to enhance stamina. Nevertheless, long term or regular consumption of kratom leads to addiction. This is because the main alkaloid of kratom, mitragynine, binds to opioid receptors and exerts a euphoric effect similar to that of morphine, which may lead to death. Due to this reason, kratom has been listed as a regulated substance in many countries including the United States, Thailand, Malaysia, Bhutan, Finland, Lithuania, Denmark, Poland, Sweden, Australia, and Myanmar. Usages of kratom carry two pharmacological effects depending on dosage. Low-dose kratom exerts a stimulating effect that refreshes the user. High-dose kratom exerts sedative effects that can lead to addiction similar to that of morphine. Despite the euphoric effect of kratom, the beneficial values of kratom to human health is indisputable. Therefore, a complete banning of kratom may cause a loss to pharmaceutical industry. Rather, a controlled or selective usage of kratom will be a better choice.
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Affiliation(s)
- Murtadha Basheer
- School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia
| | - Rana Khudhair Jasim
- School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia
| | - Gam Lay Harn
- School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia
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Striley CW, Hoeflich CC, Viegas AT, Berkowitz LA, Matthews EG, Akin LP, Iheanyi-Okeahialam C, Mansoor U, McCurdy CR. Health Effects Associated With Kratom ( Mitragyna speciosa) and Polysubstance Use: A Narrative Review. Subst Abuse 2022; 16:11782218221095873. [PMID: 35645563 PMCID: PMC9130800 DOI: 10.1177/11782218221095873] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 04/01/2022] [Indexed: 11/15/2022]
Abstract
Background Kratom (Mitragyna speciosa) consumption and associated health effects have raised debates in the United States. Although most people using this herb do not experience adverse health effects associated with kratom use, medical providers should be knowledgeable of emerging substances and concurrent, sequential, or simultaneous use of other drugs which may impact healthcare recommendations and prescribing practices. Methods The objective of this narrative review was to elucidate selected health effects associated with using kratom-either alone or with other substances. Since scientifically controlled human subjects research on kratom use is still limited, relevant case reports were also described. Results Cardiovascular, gastrointestinal, neurological, and psychiatric effects associated with kratom use were especially notable, and in-utero exposure accompanied concern regarding a neonate's risk for developing neonatal abstinence syndrome. Our ability to identify and understand the role of this herb in kratom-associated fatalities is complicated since kratom is not routinely screened for in standard forensic toxicology. If a screening is performed, it is usually for the major alkaloid, mitragynine, as a surrogate for kratom use. In addition to lacking a standard practice of screening decedents for kratom alkaloids, the association between mortality and kratom use may be confounded by polysubstance use, adulteration of kratom products, and drug-herb interactions. Conclusions Increasing medical awareness of this herb is vital to ensuring prompt administration of best-practice medical advice or treatment for people seeking information related to kratom use or for patients experiencing an adverse health effect that may be associated with using or withdrawing from kratom. Knowledge gained from continued surveillance and study of kratom and its associated health effects may assist in guiding clinical decision-making and preventing development of adverse health effects among people using kratom.
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Affiliation(s)
- Catherine W Striley
- Department of Epidemiology, College of Public Health & Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA
| | - Carolin C Hoeflich
- Department of Epidemiology, College of Public Health & Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA
| | - Andrew T Viegas
- Department of Epidemiology, College of Public Health & Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA.,College of Pharmacy, University of Florida, Gainesville, FL, USA
| | - Lindsey A Berkowitz
- Department of Epidemiology, College of Public Health & Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA.,Department of Occupational Therapy, College of Public Health & Health Professions, University of Florida, Gainesville, FL, USA
| | - Emily G Matthews
- Department of Epidemiology, College of Public Health & Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA
| | - Leyla P Akin
- Department of Epidemiology, College of Public Health & Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA.,Department of Anthropology, London School of Economics and Political Science, London, England, UK
| | - Chidinma Iheanyi-Okeahialam
- Department of Epidemiology, College of Public Health & Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA
| | - Urmeen Mansoor
- Department of Epidemiology, College of Public Health & Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA.,College of Journalism and Communications, University of Florida, Gainesville, FL, USA
| | - Christopher R McCurdy
- Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, USA
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Balarastaghi S, Delirrad M, Jafari A, Majidi M, Sadeghi M, Zare-Zardini H, Karimi G, Ghorani-Azam A. Potential benefits versus hazards of herbal therapy during pregnancy; a systematic review of available literature. Phytother Res 2022; 36:824-841. [PMID: 35023227 DOI: 10.1002/ptr.7363] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 11/03/2021] [Accepted: 12/10/2021] [Indexed: 11/07/2022]
Abstract
The use of herbal medicine has considerably grown worldwide in the past two decades. Studies have shown that the prevalence of herbal diet therapy in pregnancy ranged from 1% to 60% in different societies. Many clinical reports have shown that some herbal medicines may have toxic effects on pregnant women and their fetuses because active ingredients of some medicinal plants can readily pass through the biological barriers (e.g., placental barrier). In the present study, we aimed to systematically review the literature to discover potential benefits versus the hazards of herbal therapy during pregnancy. For this purpose, a comprehensive literature review was performed, and after the literature search and selection of the appropriate documents, the desired data were extracted and reported. From 35 articles with a total of 39,950 study population, the results showed that some medicinal plants could cause severe toxicity on mothers and fetuses, in addition to abortion during pregnancy. It was also shown that some plants may lead to developmental abnormalities or fetal death. Findings of this survey showed that some herbal medicines have toxic, teratogenic, and abortive potential, particularly in the first trimester of pregnancy because active ingredients of some medicinal plants are able to pass through the placental barrier and reach the fetus.
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Affiliation(s)
- Soudabeh Balarastaghi
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Delirrad
- Department of Forensic Medicine and Toxicology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Abbas Jafari
- Department of Clinical Toxicology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
- Cellular and Molecular Research Center, Research Institute on Cellular and Molecular Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Mohammad Majidi
- Department of Forensic Medicine and Toxicology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Mahmood Sadeghi
- Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences, Birjand, Iran
| | - Hadi Zare-Zardini
- Hematology and Oncology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Department of Sciences, Farhangian University, Isfahan, Iran
| | - Gholamreza Karimi
- Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Adel Ghorani-Azam
- Department of Forensic Medicine and Toxicology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
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Hiranita T, Obeng S, Sharma A, Wilkerson JL, McCurdy CR, McMahon LR. In vitro and in vivo pharmacology of kratom. ADVANCES IN PHARMACOLOGY (SAN DIEGO, CALIF.) 2021; 93:35-76. [PMID: 35341571 DOI: 10.1016/bs.apha.2021.10.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Kratom products have been historically and anecdotally used in south Asian countries for centuries to manage pain and opioid withdrawal. The use of kratom products has dramatically increased in the United States. More than 45 kratom alkaloids have been isolated, yet the overall pharmacology of the individual alkaloids is still not well characterized. The purpose of this chapter is to summarize in vitro and in vivo opioid activities of the primary kratom alkaloid mitragynine and its more potent metabolite 7-hydroxymitragynine. Following are experimental procedures described to characterize opioid receptor activity; receptor binding and functional assays, antinociceptive assays, operant conditioning assays, and respiratory plethysmography. The capacity of kratom alkaloids to confer tolerance and physical dependence as well as their pharmacokinetic properties are also summarized. The data reviewed here suggest that kratom products and mitragynine possess low efficacy agonist activity at the mu-opioid receptor in vivo. In addition, kratom products and mitragynine have been demonstrated to antagonize the effects of high efficacy mu-opioid agonists. The data further suggest that 7-hydroxymitragynine formed in vivo by metabolism of mitragynine may be minimally involved in the overall behavioral profile of mitragynine and kratom, whereas 7-hydroxymitragynine itself, at sufficiently high doses administered exogenously, shares many of the same abuse- and dependence-related behavioral effects associated with traditional opioid agonists. The apparent low efficacy of kratom products and mitragynine at mu-opioid receptors supports the development of these ligands as effective and potentially safe medications for opioid use disorder.
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Affiliation(s)
- Takato Hiranita
- Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, United States
| | - Samuel Obeng
- Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, United States; Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, United States
| | - Abhisheak Sharma
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, United States; Translational Drug Development Core, Clinical and Translational Sciences Institute, College of Pharmacy, University of Florida, Gainesville, FL, United States
| | - Jenny L Wilkerson
- Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, United States
| | - Christopher R McCurdy
- Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, United States; Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, United States; Translational Drug Development Core, Clinical and Translational Sciences Institute, College of Pharmacy, University of Florida, Gainesville, FL, United States
| | - Lance R McMahon
- Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, United States.
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13
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Hartley C, Bulloch M, Penzak SR. Clinical Pharmacology of the Dietary Supplement, Kratom (Mitragyna speciosa). J Clin Pharmacol 2021; 62:577-593. [PMID: 34775626 DOI: 10.1002/jcph.2001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Accepted: 11/05/2021] [Indexed: 11/10/2022]
Abstract
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.
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Affiliation(s)
- Chad Hartley
- Department of Pharmacy Practice, Harrison School of Pharmacy, Auburn University, Auburn, Alabama, 36849, United States
| | - Marilyn Bulloch
- Department of Pharmacy Practice, Harrison School of Pharmacy, Auburn University, Auburn, Alabama, 36849, United States
| | - Scott R Penzak
- Department of Pharmacy Practice, Harrison School of Pharmacy, Auburn University, Auburn, Alabama, 36849, United States
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14
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Wright ME, Ginsberg C, Parkison AM, Dubose M, Sherbondy M, Shores E. Outcomes of mothers and newborns to prenatal exposure to kratom: a systematic review. J Perinatol 2021; 41:1236-1243. [PMID: 33589723 PMCID: PMC8225511 DOI: 10.1038/s41372-021-00952-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 11/18/2020] [Accepted: 01/21/2021] [Indexed: 01/06/2023]
Abstract
Kratom is a legal, widely available substance that contains opioid agonist alkaloids. Due to the marketing of kratom as an opioid alternative for treatment of pain, anxiety, depression, or to reduce opioid withdrawal symptoms, the use of kratom has increased among persons in the USA including pregnant women. This systematic review of the peer-reviewed literature regarding kratom in relation to maternal and infant outcomes resulted in analysis of six case reports of prenatal kratom exposure. Maternal and infant withdrawal from kratom exposure was described in each case, resulting in pharmacologic treatment for both mothers and infants.
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Affiliation(s)
| | | | | | - Melissa Dubose
- Clemson University School of Nursing, Greenville, SC, USA
| | | | - Emily Shores
- Clemson University School of Nursing, Greenville, SC, USA
- University of South Carolina, School of Medicine Greenvillle, Greenville, SC, USA
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15
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Psychoactive Substances of Natural Origin: Toxicological Aspects, Therapeutic Properties and Analysis in Biological Samples. Molecules 2021; 26:molecules26051397. [PMID: 33807728 PMCID: PMC7961374 DOI: 10.3390/molecules26051397] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 02/28/2021] [Accepted: 03/02/2021] [Indexed: 12/14/2022] Open
Abstract
The consumption of new psychoactive substances (NPSs) has been increasing, and this problem affects several countries worldwide. There is a class of NPSs of natural origin, consisting of plants and fungi, which have a wide range of alkaloids, responsible for causing relaxing, stimulating or hallucinogenic effects. The consumption of some of these substances is prompted by religious beliefs and cultural reasons, making the legislation very variable or even ambiguous. However, the abusive consumption of these substances can present an enormous risk to the health of the individuals, since their metabolism and effects are not yet fully known. Additionally, NPSs are widely spread over the internet, and their appearance is very fast, which requires the development of sophisticated analytical methodologies, capable of detecting these compounds. Thus, the objective of this work is to review the toxicological aspects, traditional use/therapeutic potential and the analytical methods developed in biological matrices in twelve plant specimens (Areca catechu, Argyreia nervosa, Ayahuasca, Catha edulis, Datura stramonium, Lophophora williamsii, Mandragora officinarum, Mitragyna speciosa, Piper methysticum Forst, Psilocybe, Salvia divinorum and Tabernanthe iboga).
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16
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Vento AE, de Persis S, De Filippis S, Schifano F, Napoletano F, Corkery JM, Kotzalidis GD. Case Report: Treatment of Kratom Use Disorder With a Classical Tricyclic Antidepressant. Front Psychiatry 2021; 12:640218. [PMID: 33868054 PMCID: PMC8044355 DOI: 10.3389/fpsyt.2021.640218] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 03/05/2021] [Indexed: 12/13/2022] Open
Abstract
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.
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Affiliation(s)
- Alessandro E Vento
- ASL (Azienda Sanitaria Locale) Roma 2, Rome, Italy.,Addictions' Observatory (ODDPSS), Rome, Italy
| | | | - Sergio De Filippis
- Villa von Siebenthal Neuropsychiatric Clinic and Hospital, Genzano di Roma, Italy
| | - Fabrizio Schifano
- Psychopharmacology, Drug Misuse & Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom
| | - Flavia Napoletano
- Psychopharmacology, Drug Misuse & Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom
| | - John M Corkery
- Psychopharmacology, Drug Misuse & Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom
| | - Georgios D Kotzalidis
- Villa von Siebenthal Neuropsychiatric Clinic and Hospital, Genzano di Roma, Italy.,NESMOS Department (Neurosciences, Mental Health, and Sensory Organs), School of Medicine and Psychology, Sant'Andrea Hospital, Sapienza University, Rome, Italy
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17
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Bowe A, Kerr PL. A Complex Case of Kratom Dependence, Depression, and Chronic Pain in Opioid Use Disorder: Effects of Buprenorphine in Clinical Management. J Psychoactive Drugs 2020; 52:447-452. [PMID: 32546067 DOI: 10.1080/02791072.2020.1773586] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Mitragyna speciosa (Kratom) is a psychotropic tropical tree that is indigenous to Southeast Asia, Africa and New Guinea. Kratom has gained popularity in the United States in more recent years as an opioid agonist. Although Kratom is considered an opioid agonist with abuse potential, its use is not federally regulated. We report on a 47 year-old male presenting to our clinic for treatment of an opioid use disorder. This began with the use of prescription opioids from a doctor, and when this was no longer available this patient started using Kratom. He had used Kratom for one year to treat opioid withdrawal symptoms and chronic pain, resulting in worsening depression, anxiety and pain. He experienced tolerance and withdrawal symptoms related to Kratom. He was initiated on buprenorphine-naloxone at home with improved pain management. Four months after initiation, the patient's depression and anxiety symptoms resolved, and he was able to discontinue his antidepressant and anxiolytic medications. Kratom dependence and withdrawal appear similar to that of opioids, and may also lead to worsening depression and anxiety. Buprenorphine-naloxone may be a viable option to consider for treating opioid use disorder complicated by Kratom use, chronic pain, and depression.
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Affiliation(s)
- Adina Bowe
- Department of Behavioral Medicine and Psychiatry, West Virginia University School of Medicine-Charleston Division , Charleston, West Virginia, USA
| | - Patrick L Kerr
- Department of Behavioral Medicine and Psychiatry, West Virginia University School of Medicine-Charleston Division , Charleston, West Virginia, USA
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18
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Eastlack SC, Cornett EM, Kaye AD. Kratom-Pharmacology, Clinical Implications, and Outlook: A Comprehensive Review. Pain Ther 2020; 9:55-69. [PMID: 31994019 PMCID: PMC7203303 DOI: 10.1007/s40122-020-00151-x] [Citation(s) in RCA: 92] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Indexed: 02/06/2023] Open
Abstract
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.
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Affiliation(s)
- Steven C Eastlack
- LSU Health Sciences Center School of Medicine, 1901 Perdido Street, New Orleans, LA, 70112, USA
| | - Elyse M Cornett
- Department of Anesthesiology, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA, 71103, USA.
| | - Alan D Kaye
- Department of Anesthesiology, Louisiana State University School of Medicine, 1501 Kings Hwy, Shreveport, LA, 71103, USA
- Department of Pharmacology, Toxicology, and Neurosciences, Louisiana State University School of Medicine, 1501 Kings Hwy, Shreveport, LA, 71103, USA
- Tulane School of Medicine, New Orleans, LA, 70112, USA
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19
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Abstract
PURPOSE This article presents updated information on kratom (Mitragyna speciosa), a natural opioid with stimulant properties that is currently sold in the United States without a prescription. SUMMARY Kratom exerts opioid and alpha-2 agonistic effects, as well as anti-inflammatory and mild stimulant effects. Respiratory depression has not been commonly reported, but kratom does cause a host of adverse effects. While kratom may have a role in patients who are in chronic pain or dependent on opioid painkillers or heroin, this needs to be established in clinical trials. Kratom may have drug interactions as both a cytochrome P-450 system substrate and inhibitor. Kratom does not appear in normal drug screens and, especially when ingested with other substances of abuse, may not be recognized as an agent of harm. There are numerous cases of death in kratom users, but many involved polypharmaceutical ingestions. There are assessments where people have been unable to stop using kratom therapy and withdrawal signs/symptoms occurred in patients or their newborn babies after kratom cessation. Both banning and failure to ban kratom places people at risk; a middle-ground alternative, placing it behind the pharmacy counter, might be useful. CONCLUSION Kratom has a unique pharmacologic profile that might offer advantages over other opioids, but its high abuse liability, potential for drug interactions and adverse events, and inadequate research into the balance of benefits to harm are concerning. There is mounting information on the adverse events associated with kratom use and potential treatments that can be useful to clinicians.
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Affiliation(s)
- C Michael White
- University of Connecticut School of Pharmacy, Storrs, CT, and Department of Pharmacy, Hartford Hospital, Hartford, CT
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20
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Metastasio A, Prevete E, Singh D, Grundmann O, Prozialeck WC, Veltri C, Bersani G, Corazza O. Can Kratom ( Mitragyna speciosa) Alleviate COVID-19 Pain? A Case Study. Front Psychiatry 2020; 11:594816. [PMID: 33329145 PMCID: PMC7717955 DOI: 10.3389/fpsyt.2020.594816] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 10/27/2020] [Indexed: 01/14/2023] Open
Abstract
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.
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Affiliation(s)
- Antonio Metastasio
- School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom.,NHS Camden and Islington Trust, London, United Kingdom
| | - Elisabeth Prevete
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Darshan Singh
- Centre for Drug Research, Universiti Sains Malaysia, Minden, Malaysia
| | - Oliver Grundmann
- Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, United States
| | - Walter C Prozialeck
- Department of Pharmacology, Midwestern University, Downers Grove, IL, United States
| | - Charles Veltri
- Department of Pharmaceutical Sciences, Midwestern University, Glendale, AZ, United States
| | - Giuseppe Bersani
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Ornella Corazza
- School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom.,Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
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21
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Kratom from Head to Toe—Case Reviews of Adverse Events and Toxicities. CURRENT EMERGENCY AND HOSPITAL MEDICINE REPORTS 2019. [DOI: 10.1007/s40138-019-00194-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Abstract
Purpose of Review
This review describes case reports for patients with kratom-associated adverse events in order to assist clinicians with patient management. A stepwise approach is proposed for assessing active kratom users as well as considerations for the management of toxicities or withdrawal.
Recent Findings
Multiple in vitro and in vivo studies illustrate the pharmacologic and toxicologic effects of kratom extract. No randomized controlled trials in humans exist that assess the safety and efficacy of the substance. Cross-sectional surveys from active users and reports from poison control centers have shown acute and chronic physiological and psychological adverse events.
Summary
Reports of adverse effects associated with kratom use have demonstrated hypothyroidism, hypogonadism, hepatitis, acute respiratory distress syndrome, posterior reversible encephalopathy syndrome, seizure, and coma. Overdose toxidrome leads to respiratory failure, cardiac arrest, and fatalities. Adult and neonatal withdrawal symptoms have also occurred. Clinicians should be aware of the risks and benefits of kratom use.
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22
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Corkery JM, Streete P, Claridge H, Goodair C, Papanti D, Orsolini L, Schifano F, Sikka K, Körber S, Hendricks A. Characteristics of deaths associated with kratom use. J Psychopharmacol 2019; 33:1102-1123. [PMID: 31429622 DOI: 10.1177/0269881119862530] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Kratom (Mitragyna speciosa Korth) use has increased in Western countries, with a rising number of associated deaths. There is growing debate about the involvement of kratom in these events. AIMS This study details the characteristics of such fatalities and provides a 'state-of-the-art' review. METHODS UK cases were identified from mortality registers by searching with the terms 'kratom', 'mitragynine', etc. Databases and online media were searched using these terms and 'death', 'fatal*', 'overdose', 'poisoning', etc. to identify additional cases; details were obtained from relevant officials. Case characteristics were extracted into an Excel spreadsheet, and analysed employing descriptive statistics and thematic analysis. RESULTS Typical case characteristics (n = 156): male (80%), mean age 32.3 years, White (100%), drug abuse history (95%); reasons for use included self-medication, recreation, relaxation, bodybuilding, and avoiding positive drug tests. Mitragynine alone was identified/implicated in 23% of cases. Poly substance use was common (87%), typically controlled/recreational drugs, therapeutic drugs, and alcohol. Death cause(s) included toxic effects of kratom ± other substances; underlying health issues. CONCLUSIONS These findings add substantially to the knowledge base on kratom-associated deaths; these need systematic, accurate recording. Kratom's safety profile remains only partially understood; toxic and fatal levels require quantification.
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Affiliation(s)
- John M Corkery
- Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, Department of Clinical and Pharmaceutical Sciences, University of Hertfordshire, Hatfield, UK
| | | | - Hugh Claridge
- National Programme on Substance Abuse Deaths, Population Health Research Institute, St George's, University of London, London, UK
| | - Christine Goodair
- National Programme on Substance Abuse Deaths, Population Health Research Institute, St George's, University of London, London, UK
| | - Duccio Papanti
- Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, Department of Clinical and Pharmaceutical Sciences, University of Hertfordshire, Hatfield, UK
| | - Laura Orsolini
- Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, Department of Clinical and Pharmaceutical Sciences, University of Hertfordshire, Hatfield, UK
| | - Fabrizio Schifano
- Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, Department of Clinical and Pharmaceutical Sciences, University of Hertfordshire, Hatfield, UK
| | - Kanav Sikka
- Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, Department of Clinical and Pharmaceutical Sciences, University of Hertfordshire, Hatfield, UK
| | - Sophie Körber
- Department of Pharmaceutical Science, University of Basel, Basel, Switzerland
| | - Amy Hendricks
- Retired Forensic Pathology Technician, Santa Clara County, CA, USA
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23
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Abdullah HMA, Haq I, Lamfers R. Cardiac arrest in a young healthy male patient secondary to kratom ingestion: is this 'legal high' substance more dangerous than initially thought ? BMJ Case Rep 2019; 12:e229778. [PMID: 31326902 PMCID: PMC6663180 DOI: 10.1136/bcr-2019-229778] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/05/2019] [Indexed: 12/17/2022] Open
Abstract
Kratom is a psychoactive herb that has stimulant properties at low doses and has opioid-like properties at higher doses. It has been used for centuries in southeast Asia as a stimulant but has gained increasing popularity as a substitute for opioids in western countries as it is easily available. As most cases of kratom use involve other drugs too, the Food and Drug Administration (FDA) has stopped short of restricting kratom due to difficulty in assessing the adverse effects of kratom alone. We present the case of a young healthy 35-year-old man who suffered a cardiac arrest due to kratom use with no other coingestants. He was subsequently intubated and found to have systolic dysfunction and small brain infarcts. Fortunately, he made a successful recovery and was discharged after a stay at thebehavioural health centre. Our case highlights the potential adverse effects of kratom and the need to regulate its use.
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Affiliation(s)
| | - Iqra Haq
- Internal Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, South Dakota, USA
| | - Randall Lamfers
- Internal Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, South Dakota, USA
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24
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Meireles V, Rosado T, Barroso M, Soares S, Gonçalves J, Luís Â, Caramelo D, Simão AY, Fernández N, Duarte AP, Gallardo E. Mitragyna speciosa: Clinical, Toxicological Aspects and Analysis in Biological and Non-Biological Samples. MEDICINES 2019; 6:medicines6010035. [PMID: 30836609 PMCID: PMC6473843 DOI: 10.3390/medicines6010035] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 02/24/2019] [Accepted: 02/27/2019] [Indexed: 02/07/2023]
Abstract
The abuse of psychotropic substances is a well-known phenomenon, and many of them are usually associated with ancestral traditions and home remedies. This is the case of Mitragyna speciosa (kratom), a tropical tree used to improve work performance and to withstand great heat. According to several published studies, the main reasons for kratom consumption involve improving sexual performance and endurance, but also social and recreational uses for the feeling of happiness and euphoria; it is also used for medical purposes as a pain reliever, and in the treatment of diarrhea, fever, diabetes, and hypertension. However, this plant has gained more popularity amongst young people over the last years. Since it is available on the internet for purchase, its use is now widely as a drug of abuse, namely as a new psychoactive substance, being a cheaper alternative to opioids that does not require medical prescription in most countries. According to internet surveys by the European Monitoring Centre for Drugs and Drug Addiction in 2008 and 2011, kratom was one of the most widely supplied new psychoactive substances. The composition of kratom is complex; in fact, more than 40 different alkaloids have been identified in Mitragyna speciosa so far, the major constituent being mitragynine, which is exclusive to this plant. Besides mitragynine, alkaloids such as corynantheidine and 7-hydroxamitragynine also present pharmacological effects, a feature that may be attributed to the remaining constituents as well. The main goal of this review is not only to understand the origin, chemistry, consumption, and analytical methodologies for analysis and mechanism of action, but also the use of secondary metabolites of kratom as therapeutic drugs and the assessment of potential risks associated with its consumption, in order to aid health professionals, toxicologists, and police authorities in cases where this plant is present.
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Affiliation(s)
- Vânia Meireles
- Centro de Investigação em Ciências da Saúde, Faculdade de Ciências da Saúde da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilhã, Portugal.
| | - Tiago Rosado
- Centro de Investigação em Ciências da Saúde, Faculdade de Ciências da Saúde da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilhã, Portugal.
| | - Mário Barroso
- Serviço de Química e Toxicologia Forenses, Instituto de Medicina Legal e Ciências Forenses-Delegação do Sul, 1169-201 Lisboa, Portugal.
| | - Sofia Soares
- Centro de Investigação em Ciências da Saúde, Faculdade de Ciências da Saúde da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilhã, Portugal.
| | - Joana Gonçalves
- Centro de Investigação em Ciências da Saúde, Faculdade de Ciências da Saúde da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilhã, Portugal.
| | - Ângelo Luís
- Centro de Investigação em Ciências da Saúde, Faculdade de Ciências da Saúde da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilhã, Portugal.
| | - Débora Caramelo
- Centro de Investigação em Ciências da Saúde, Faculdade de Ciências da Saúde da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilhã, Portugal.
| | - Ana Y Simão
- Centro de Investigação em Ciências da Saúde, Faculdade de Ciências da Saúde da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilhã, Portugal.
| | - Nicolás Fernández
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Toxicología y Química Legal, Laboratorio de Asesoramiento Toxicológico Analítico (CENATOXA). Junín 956 7mo piso. Ciudad Autónoma de Buenos Aires (CABA), Buenos Aires C1113AAD, Argentina.
| | - Ana Paula Duarte
- Centro de Investigação em Ciências da Saúde, Faculdade de Ciências da Saúde da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilhã, Portugal.
| | - Eugenia Gallardo
- Centro de Investigação em Ciências da Saúde, Faculdade de Ciências da Saúde da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilhã, Portugal.
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25
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Gauvin DV, Zimmermann ZJ. A reply to Henningfield, Fant & Wang (2018): regulatory action to control kratom is long overdue. Psychopharmacology (Berl) 2019; 236:861-863. [PMID: 30415275 DOI: 10.1007/s00213-018-5112-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 11/05/2018] [Indexed: 02/02/2023]
Affiliation(s)
- David V Gauvin
- Neurobehavioral Sciences Department, Abuse Liability and Ototoxicity, MPI Research (A Charles River Company), 54943 North Main St., Mattawan, MI, 49071, USA.
| | - Zachary J Zimmermann
- Neurobehavioral Sciences Department, Abuse Liability and Ototoxicity, MPI Research (A Charles River Company), 54943 North Main St., Mattawan, MI, 49071, USA
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Martins F, Oppolzer D, Santos C, Barroso M, Gallardo E. Opioid Use in Pregnant Women and Neonatal Abstinence Syndrome-A Review of the Literature. TOXICS 2019; 7:E9. [PMID: 30781484 PMCID: PMC6468487 DOI: 10.3390/toxics7010009] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 02/10/2019] [Accepted: 02/13/2019] [Indexed: 02/07/2023]
Abstract
Opiate use during pregnancy has been an increasing problem over the last two decades, making it an important social and health concern. The use of such substances may have serious negative outcomes in the newborn, and clinical and cognitive conditions have been reported, including neonatal abstinence syndrome, developmental problems, and lower cognitive performance. These conditions are common when opiates are used during pregnancy, making the prescription of these kinds of drugs problematic. Moreover, the mother may develop opiate addiction, thus, increasing the likelihood of the infant being born with any of those conditions. This paper reviews the use of opiates during pregnancy and focuses mainly on the neonatal abstinence syndrome. First, the commonly prescribed opiates will be identified, namely those usually involved in cases of addiction and/or neonatal abstinence syndrome. Second, published approaches to deal with those problems will be presented and discussed, including the treatment of both the mother and the infant. Finally, we will outline the treatments that are safest and most efficient, and will define future goals, approaches, and research directions for the scientific community regarding this problem.
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Affiliation(s)
- Fábio Martins
- Centro de Investigação em Ciências da Saúde, Faculdade de Ciências da Saúde da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilhã, Portugal.
| | - David Oppolzer
- Centro de Investigação em Ciências da Saúde, Faculdade de Ciências da Saúde da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilhã, Portugal.
| | - Catarina Santos
- Centro de Investigação em Ciências da Saúde, Faculdade de Ciências da Saúde da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilhã, Portugal.
| | - Mário Barroso
- Serviço de Química e Toxicologia Forenses, Instituto de Medicina Legal e Ciências Forenses-Delegação do Sul, 1150-334 Lisboa, Portugal.
| | - Eugenia Gallardo
- Centro de Investigação em Ciências da Saúde, Faculdade de Ciências da Saúde da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilhã, Portugal.
- Laboratório de Fármaco-Toxicologia-UBIMedical, Universidade da Beira Interior, 6200-284 Covilhã, Portugal.
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