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Suspected Adulteration of Commercial Kratom Products with 7-Hydroxymitragynine

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Abstract

Introduction

Kratom (Mitragyna speciosa), a plant native to Southeast Asia, has been used for centuries for its stimulant and opium-like effects. Mitragynine and 7-hydroxymitragynine, exclusive to M. speciosa, are the alkaloids primary responsible for Kratom's biologic and psychoactive profile, and likely contribute to its problematic use. We purchased several commercially available Kratom analogs for analysis and through our results, present evidence of probable adulteration with the highly potent and addictive plant alkaloid, 7-hydroxymitragynine.

Methods

A simple and sensitive LC-MS/MS method was developed for simultaneous quantification of mitragynine and 7-hydroxymitragynine in methanol extract of marketed Kratom supplements.

Results

We found multiple commercial Kratom products to have concentrations of 7-hydroxymitragynine that are substantially higher than those found in raw M. speciosa leaves.

Conclusions

We have found multiple packaged commercial Kratom products likely to contain artificially elevated concentrations of 7-hydroxymitragynine, the alkaloid responsible for M. speciosa's concerning mechanistic and side effect profile. This study describes a unique form of product adulteration, which stresses the importance of increased dietary supplement oversight of Kratom-containing supplements.

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References

  1. Suwanlert S. A study of Kratom eaters in Thailand. Bull Narc. 1975;27(3):21–7.

  2. Warner ML, Kaufman NC, Grundmann O. The pharmacology and toxicology of Kratom: from traditional herb to drug of abuse. Int J Legal Med. 2016;130(1):127–38.

  3. Jansen K, Prast CJ. Ethnopharmacology of Kratom and the Mitragyna alkaloids. J Ethnopharmacol. 1988;23(1):115–119.

  4. Grewal KS. The effect of mitragynine on man. Br J Med Psychol. 2011;12(1):41–58.

    Article  Google Scholar 

  5. Matsumoto K, Mizowaki M, Suchitra T, Takayama H, Sakai S-I, Aimi N, et al. Antinociceptive action of mitragynine in mice: evidence for the involvement of supraspinal opioid receptors. Life Sci. 1996;59(14):1149–55.

    Article  CAS  PubMed  Google Scholar 

  6. Kratom (Mitragyna speciosa) Drug Profile. European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). 2015. http://www.emcdda.europa.eu/publications/drug-profiles/kratom. Accessed 16 Jan 2016.

  7. Kratom (Mitragyna speciosa Korth). Drug Enforcement Administration, Office of Diversion Control, Drug & Chemical Evaluation Section. 2013. http://www.deadiversion.usdoj.gov/drug_chem_info/kratom.pdf. Accessed 16 Jan 2016.

  8. Special Report: Opiates and Related Drugs Reported in NFLIS, 2009–2014. U.S. Department Of Justice, Drug Enforcement Administration, Office of Diversion Control. 2016. https://www.nflis.deadiversion.usdoj.gov/DesktopModules/ReportDownloads/Reports/NFLIS-SR-Opioids-Rev.pdf. Accessed 21 June 2016.

  9. Huus K. Asian leaf “kratom” making presence felt in US emergency rooms. NBC News. 2012. http://usnews.nbcnews.com/_news/2012/03/19/10760892-asian-leaf-kratom-making-presence-felt-in-us-emergency-rooms. Accessed 10 May 2016.

  10. Boyer EW, Babu KM, Adkins JE, McCurdy CR, Halpern JH. Self-treatment of opioid withdrawal using Kratom (Mitragyna speciosa korth). Addiction. 2008;103(6):1048–50.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Prozialeck WC, Jivan JK, Andurkar SV. Pharmacology of Kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects. J Am Osteopath Assoc. 2012;112(12):792–9.

    PubMed  Google Scholar 

  12. Dargan P, Wood D. Novel Psychoactive Substances. Boston: Academic; 2013.

  13. Hassan Z, Muzaimi M, Navaratnam V, Yusoff NHM, Suhaimi FW, Vadivelu R, et al. From Kratom to mitragynine and its derivatives: physiological and behavioural effects related to use, abuse, and addiction. Neurosci Biobehav Rev. 2013;37(2):138–51.

    Article  CAS  PubMed  Google Scholar 

  14. Cinosi E, Martinotti G, Simonato P, Singh D, Demetrovics Z, Roman-Urrestarazu A, et al. Following “the roots” of Kratom (Mitragyna speciosa): the evolution of an enhancer from a traditional use to increase work and productivity in Southeast Asia to a recreational psychoactive drug in western countries. Biomed Res Int. 2015;2015:1–11.

  15. Shellard EJ. The alkaloids of Mitragyna with special reference to those of Mitragyna speciosa, Korth. Bull Narc. 1974;26(2):41–55.

    CAS  PubMed  Google Scholar 

  16. Ponglux D, Wongseripipatana S, Takayama H, Kikuchi M, Kurihara M, Kitajima M, et al. A new indole alkaloid, 7 alpha-hydroxy-7H-mitragynine, from Mitragyna speciosa in Thailand. Planta Med. 1994;60(06):580–1.

    Article  CAS  PubMed  Google Scholar 

  17. Thongpradichote S, Matsumoto K, Tohda M, Takayama H, Aimi N, Sakai S, et al. Identification of opioid receptor subtypes in antinociceptive actions of supraspinally-administered mitragynine in mice. Life Sci. 1998;62(16):1371–8.

    Article  CAS  PubMed  Google Scholar 

  18. Matsumoto K, Mizowaki M, Suchitra T, Murakami Y, Takayama H, Sakai S-I, et al. Central antinociceptive effects of mitragynine in mice: contribution of descending noradrenergic and serotonergic systems. Eur J Pharmacol. 1996;317(1):75–81.

    Article  CAS  PubMed  Google Scholar 

  19. Gregory TB. Hydromorphone: evolving to meet the challenges of today’s health care environment. Clin Ther. 2013;35(12):2007–27.

    Article  CAS  PubMed  Google Scholar 

  20. Matsumoto K, Horie S, Ishikawa H, Takayama H, Aimi N, Ponglux D, et al. Antinociceptive effect of 7-hydroxymitragynine in mice: discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa. Life Sci. 2004;74(17):2143–55.

    Article  CAS  PubMed  Google Scholar 

  21. Takayama H, Ishikawa H, Kurihara M, Kitajima M, Aimi N, Ponglux D, et al. Studies on the synthesis and opioid agonistic activities of mitragynine-related indole alkaloids: discovery of opioid agonists structurally different from other opioid ligands. J Med Chem. 2002;45(9):1949–56.

    Article  CAS  PubMed  Google Scholar 

  22. Horie S, Koyama F, Takayama H, Ishikawa H, Aimi N, Ponglux D, et al. Indole alkaloids of a Thai medicinal herb, Mitragyna speciosa, that has opioid agonistic effect in guinea-pig ileum. Planta Med. 2005;71(3):231–6.

    Article  CAS  PubMed  Google Scholar 

  23. Adkins JE, Boyer EW, McCurdy CR. Mitragyna speciosa, a psychoactive tree from Southeast Asia with opioid activity. Curr Top Med Chem. 2011;11(9):1165–75.

    Article  CAS  PubMed  Google Scholar 

  24. Roche KM, Hart K, Sangalli B. Kratom: a case of a legal high. Clin Toxicol. 2008;46(7):598.

    Google Scholar 

  25. McWhirter L, Morris S. A case report of inpatient detoxification after Kratom (Mitragyna speciosa) dependence. Eur Addict Res. 2010;16(4):229–31.

    Article  PubMed  Google Scholar 

  26. Babu KM, McCurdy CR, Boyer EW. Opioid receptors and legal highs: Salvia divinorum and Kratom. Clin Toxicol (Phila). 2008;46(2):146–52.

    Article  CAS  Google Scholar 

  27. Matsumoto K, Horie S, Takayama H, Ishikawa H, Aimi N, Ponglux D, et al. Antinociception, tolerance and withdrawal symptoms induced by 7-hydroxymitragynine, an alkaloid from the Thai medicinal herb Mitragyna speciosa. Life Sci. 2005;78(1):2–7.

    Article  CAS  PubMed  Google Scholar 

  28. Narita M, Funada M, Suzuki T. Regulations of opioid dependence by opioid receptor types. Pharmacol Ther. 2001;89(1):1–15.

    Article  CAS  PubMed  Google Scholar 

  29. Matthes HW, Maldonado R, Simonin F, Valverde O, Slowe S, Kitchen I, et al. Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid-receptor gene. Nature. 1996;383(6603):819–23.

    Article  CAS  PubMed  Google Scholar 

  30. Kikura-Hanajiri R, Kawamura M, Maruyama T, Kitajima M, Takayama H, Goda Y. Simultaneous analysis of mitragynine, 7-hydroxymitragynine, and other alkaloids in the psychotropic plant “Kratom” (Mitragyna speciosa) by LC-ESI-MS. Forensic Toxicol. 2009;27(2):67–74.

    Article  CAS  Google Scholar 

  31. Grewal KS. Observations on the pharmacology of mitragynine. American Society for Pharmacology and Experimental Therapeutics. J Pharmacol Exp Ther. 1932;46(3):251–71.

    CAS  Google Scholar 

  32. Goh TB, Koh RY, Mordi MN, Mansor SM. Antioxidant value and antiproliferative efficacy of mitragynine and a silane reduced analogue. Asian Pac J Cancer Prev. 2014;15(14):5659–65.

    Article  PubMed  Google Scholar 

  33. Parthasarathy S, Bin Azizi J, Ramanathan S, Ismail S, Sasidharan S, Said MI, et al. Evaluation of antioxidant and antibacterial activities of aqueous, methanolic and alkaloid extracts from Mitragyna speciosa (Rubiaceae Family) leaves. Molecules. Mol Divers Preserv Int. 2009;14(10):3964–74.

    CAS  Google Scholar 

  34. Utar Z, Majid MIA, Adenan MI, Jamil MFA, Lan TM. Mitragynine inhibits the COX-2 mRNA expression and prostaglandin E2 production induced by lipopolysaccharide in RAW264.7 macrophage cells. J Ethnopharmacol. 2011;136(1):75–82.

    Article  CAS  PubMed  Google Scholar 

  35. Burkill IH, Haniff M. Malay village medicine, prescriptions collected. Gard Bull. 1930;6:165–321.

    Google Scholar 

  36. Tanguay P. Kratom in Thailand. Legis Reform Drug Policies. 2011;13:1–16.

    Google Scholar 

  37. Idayu NF, Hidayat MT, Moklas MAM, Sharida F, Raudzah ARN, Shamima AR, et al. Antidepressant-like effect of mitragynine isolated from Mitragyna speciosa Korth in mice model of depression. Phytomedicine. 2011;18(5):402–7.

    Article  PubMed  Google Scholar 

  38. Harizal SN, Mansor SM, Hasnan J, Tharakan JKJ, Abdullah J. Acute toxicity study of the standardized methanolic extract of Mitragyna speciosa Korth in rodent. J Ethnopharmacol. 2010;131(2):404–9.

    Article  CAS  PubMed  Google Scholar 

  39. Kumarnsit E, Keawpradub N, Nuankaew W. Effect of Mitragyna speciosa aqueous extract on ethanol withdrawal symptoms in mice. Fitoterapia. 2007;78(3):182–5.

    Article  PubMed  Google Scholar 

  40. Vicknasingam B, Narayanan S, Beng GT, Mansor SM. The informal use of ketum (Mitragyna speciosa) for opioid withdrawal in the northern states of peninsular Malaysia and implications for drug substitution therapy. Int J Drug Policy. 2010;21(4):283–8.

    Article  PubMed  Google Scholar 

  41. Ahmad K, Aziz Z. Mitragyna speciosa use in the northern states of Malaysia: a cross-sectional study. J Ethnopharmacol. 2012;141(1):446–50.

    Article  PubMed  Google Scholar 

  42. Shellard EJ. Ethnopharmacology of Kratom and the Mitragyna alkaloids. J Ethnopharmacol. 1989;25(1):123–4.

    Article  CAS  PubMed  Google Scholar 

  43. Erowid. Kratom Dosage. The Vaults of Erowid. 2015. https://www.erowid.org/plants/kratom/kratom_dose.shtml. Accessed 23 Jan 2016.

  44. Erowid. Kratom (Mitragyna speciosa) Effects. The Vaults of Erowid. 2016. https://www.erowid.org/plants/kratom/kratom_effects.shtml. Accessed 23 Jan 2016.

  45. Thuan LC. Addiction to Mitragyna speciosa. Proc Alumni Assoc. 1957;10:322–4.

    Google Scholar 

  46. Yusoff NHM, Suhaimi FW, Vadivelu RK, Hassan Z, Rümler A, Rotter A, et al. Abuse potential and adverse cognitive effects of mitragynine (Kratom. Addict Biol. 2014;21:98–110.

    Article  PubMed  Google Scholar 

  47. Nelsen JL, Lapoint J, Hodgman MJ, Aldous KM. Seizure and coma following Kratom (Mitragynina speciosa Korth) exposure. J Med Toxicol. 2010;6(4):424–6.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Lu J, Wei H, Wu J, Jamil MFA, Tan ML, Adenan MI, et al. Evaluation of the cardiotoxicity of mitragynine and its analogues using human induced pluripotent stem cell-derived cardiomyocytes. Clin Toxicol. 2014;9(12):e115648.

    Google Scholar 

  49. Cabellon M, Aris R, Pathak V. Adult respiratory distress syndrome secondary to the use of herbal drug kratom. Am J Respir Crit Care Med. 2014;189:A6492.

    Google Scholar 

  50. Sheleg SV, Collins GB. A coincidence of addiction to “Kratom” and severe primary hypothyroidism. J Addict Med. 2011;5(4):300–1.

    Article  PubMed  Google Scholar 

  51. Kapp FG, Maurer HH, Auwärter V, Winkelmann M, Hermanns-Clausen M. Intrahepatic cholestasis following abuse of powdered Kratom (Mitragyna speciosa). J Med Toxicol. 2011;7(3):227–31.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Lu J, Wei H, Wu J, Jamil M, Tan ML, Adenan MI. Evaluation of the cardiotoxicity of mitragynine and its analogues using human induced pluripotent stem cell-derived cardiomyocytes. PLoS One. 2014;9(12):e115648.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Holler JM, Vorce SP, McDonough-Bender PC, Joseph Magluilo J, Solomon CJ, Levine B. A drug toxicity death involving propylhexedrine and mitragynine. J Anal Toxicol. 2011;35(1):54–9.

    Article  CAS  PubMed  Google Scholar 

  54. Tungtananuwat W, Lawanprasert S. Fatal 4×100: homemade Kratom juice cocktail. J Health Res. 2010;24(1):43–7.

    Google Scholar 

  55. Neerman MF, Frost RE, Deking J. A drug fatality involving Kratom. J Forensic Sci. 2013;58(s1):S278–9.

    Article  PubMed  Google Scholar 

  56. McIntyre IM, Trochta A, Stolberg S, Campman SC. Mitragynine “Kratom” related fatality: a case report with postmortem concentrations. J Anal Toxicol. 2015;39(2):152–5.

    Article  CAS  PubMed  Google Scholar 

  57. Kronstrand R, Roman M, Thelander G, Eriksson A. Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend krypton. J Anal Toxicol. 2011;35(4):242–7.

    Article  CAS  PubMed  Google Scholar 

  58. Scott TM, Yeakel JK, Logan BK. Identification of mitragynine and O-desmethyltramadol in Kratom and legal high products sold online. Drug Test Anal. 2014;6(9):959–63.

    Article  CAS  PubMed  Google Scholar 

  59. Dietary Supplement Health and Education Act of 1994. National Institutes of Health Office of Dietary Supplements. 1994. https://ods.od.nih.gov/About/DSHEA_Wording.aspx. Accessed 31 Jan 2016.

  60. Petróczi A, Ocampo JAV, Shah I, Jenkinson C, New R, James RA, et al. Russian roulette with unlicensed fat-burner drug 2,4-dinitrophenol (DNP): evidence from a multidisciplinary study of the internet, bodybuilding supplements and DNP users. Subst Abuse Treat Prev Policy. 2015;10(1).

  61. Rebiere H, Guinot P, Civade C, Bonnet P-A, Nicolas A. Detection of hazardous weight-loss substances in adulterated slimming formulations using ultra-high-pressure liquid chromatography with diode-array detection. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2012;29(2):161–71.

    Article  CAS  PubMed  Google Scholar 

  62. Venhuis BJ, Zwaagstra ME, Van den Berg J. Trends in drug substances detected in illegal weight-loss medicines and dietary supplements. RIVM Report. 2009;370030002:1–37.

  63. Jung J, Hermanns-Clausen M, Weinmann W. Anorectic sibutramine detected in a Chinese herbal drug for weight loss. Forensic Sci Int. 2006;161(2–3):221–2.

    Article  CAS  PubMed  Google Scholar 

  64. Wang J, Chen B, Yao S. Analysis of six synthetic adulterants in herbal weight-reducing dietary supplements by LC electrospray ionization-MS. Food Addit Contam. 2008;25(7):822–30.

    Article  CAS  Google Scholar 

  65. Vaysse J, Balayssac S, Gilard V, Desoubdzanne D, Malet-Martino M, Martino R. Analysis of adulterated herbal medicines and dietary supplements marketed for weight loss by DOSY 1H-NMR. Food Addit Contam. 2010;27(7):903–16.

    Article  CAS  Google Scholar 

  66. Shi Y, Sun C, Gao B, Sun A. Development of a liquid chromatography tandem mass spectrometry method for simultaneous determination of eight adulterants in slimming functional foods. J Chromatogr A. 2011;1218(42):7655–62.

    Article  CAS  PubMed  Google Scholar 

  67. De Carvalho LM, Cohen PA, Silva CV, Moreira APL, Falcão TM, Molin TRD, et al. A new approach to determining pharmacologic adulteration of herbal weight loss products. Food Addit Contam: Part A. 2012;29(11):1661–7.

    Article  CAS  Google Scholar 

  68. Park S-R, Lee JG, Roh SH, Kim G, Kwon CH, Park HR, et al. Determination of PDE-5 inhibitors and appetite suppressants in adulterated dietary supplements using LC/PDA and LC/MS. Food Addit Contam: Part B. 2012;5(1):29–32.

    Article  CAS  Google Scholar 

  69. Song F, Monroe D, El-Demerdash A, Palmer C. Screening for multiple weight loss and related drugs in dietary supplement materials by flow injection tandem mass spectrometry and their confirmation by liquid chromatography tandem mass spectrometry. J Pharm Biomed Anal. 2014;88:136–43.

    Article  CAS  PubMed  Google Scholar 

  70. Kim HJ, Lee JH, Park HJ, Cho S-H, Cho S, Kim WS. Monitoring of 29 weight loss compounds in foods and dietary supplements by LC-MS/MS. Food Addit Contam: Part A. 2014;31(5):777–83.

    Article  CAS  Google Scholar 

  71. Hachem R, Malet-Martino M, Gilard V. First identification and quantification of lorcaserin in an herbal slimming dietary supplement. J Pharm Biomed Anal. 2014;98:94–9.

    Article  CAS  PubMed  Google Scholar 

  72. Reeuwijk NM, Venhuis BJ, de Kaste D, Hoogenboom RLAP, Rietjens IMCM, Martena MJ. Active pharmaceutical ingredients detected in herbal food supplements for weight loss sampled on the Dutch market. Food Addit Contam: Part A. 2014;31(11):1783–93.

    Article  CAS  Google Scholar 

  73. Mathon C, Ankli A, Reich E, Bieri S, Christen P. Screening and determination of sibutramine in adulterated herbal slimming supplements by HPTLC-UV densitometry. Food Addit Contam: Part A. 2013;31(1):15–20.

    Article  Google Scholar 

  74. Strano-Rossi S, Odoardi S, Castrignanò E, Serpelloni G, Chiarotti M. Liquid chromatography–high resolution mass spectrometry (LC–HRMS) determination of stimulants, anorectic drugs and phosphodiesterase 5 inhibitors (PDE5I) in food supplements. J Pharm Biomed Anal. 2015;106:144–52.

    Article  CAS  PubMed  Google Scholar 

  75. Maughan RJ. Contamination of dietary supplements and positive drug tests in sport. J Sports Sci. 2005;23(9):883–9.

    Article  CAS  PubMed  Google Scholar 

  76. Maughan RJ, Greenhaff PL, Hespel P. Dietary supplements for athletes: emerging trends and recurring themes. J Sports Sci. 2011;29(suppl 1):S57–66.

    Article  PubMed  Google Scholar 

  77. Geyer H, Parr MK, Mareck U, Reinhart U, Schrader Y, Schänzer W. Analysis of non-hormonal nutritional supplements for anabolic-androgenic steroids—results of an international study. Int J Sports Med. 2004;25(2):124–9.

    Article  CAS  PubMed  Google Scholar 

  78. Geyer H, Parr MK, Koehler K, Mareck U, Schänzer W, Thevis M. Nutritional supplements cross-contaminated and faked with doping substances. J Mass Spectrom. 2008;43(7):892–902.

    Article  CAS  PubMed  Google Scholar 

  79. van der Merwe PJ, Grobbelaar E. Unintentional doping through the use of contaminated nutritional supplements. S Afr Med J. 2005;95(7):510–1.

    PubMed  Google Scholar 

  80. Pipe A, Ayotte C. Nutritional supplements and doping. Clin J Sport Med. 2002;12(4):245–9.

    Article  PubMed  Google Scholar 

  81. Campbell N, Clark JP, Stecher VJ, Thomas JW, Callanan AC, Donnelly BF, et al. Adulteration of purported herbal and natural sexual performance enhancement dietary supplements with synthetic phosphodiesterase type 5 inhibitors. J Sex Med. 2013;10(7):1842–9.

    Article  PubMed  Google Scholar 

  82. Gratz SR, Flurer CL, Wolnik KA. Analysis of undeclared synthetic phosphodiesterase-5 inhibitors in dietary supplements and herbal matrices by LC–ESI–MS and LC–UV. J Pharm Biomed Anal. 2004;36(3):525–33.

    Article  CAS  PubMed  Google Scholar 

  83. Ng CS, Law TY, Cheung YK, Ng PC, Choi KK. Development of a screening method for the detection of analogues of sildenafil and vardenafil by the use of liquid chromatograph coupled with triple quadrupole linear ion trap mass spectrometer. analytical methods. Royal Soc Chem. 2010;2(7):890–6.

    CAS  Google Scholar 

  84. Savaliya AA, Shah RP, Prasad B, Singh S. Screening of Indian aphrodisiac ayurvedic/herbal healthcare products for adulteration with sildenafil, tadalafil and/or vardenafil using LC/PDA and extracted ion LC–MS/TOF. J Pharm Biomed Anal. 2010;52(3):406–9.

    Article  CAS  PubMed  Google Scholar 

  85. Zhang Y, Huang Z, Ding L, Yan H, Wang M, Zhu S. Simultaneous determination of yohimbine, sildenafil, vardenafil and tadalafil in dietary supplements using high-performance liquid chromatography-tandem mass spectrometry. J Sep Sci. 2010;33(14):2109–14.

    Article  CAS  PubMed  Google Scholar 

  86. Toomey VM, Litzau JJ, Flurer CL. Isolation and structural characterization of two tadalafil analogs found in dietary supplements. J Pharm Biomed Anal. 2012;59:50–7.

    Article  CAS  PubMed  Google Scholar 

  87. Ren Y, Wu C, Zhang J. Simultaneous screening and determination of 18 illegal adulterants in herbal medicines and health foods for male sexual potency by ultra-fast liquid chromatography-electrospray ionization tandem mass spectrometry. J Sep Sci. 2012;35(21):2847–57.

    Article  CAS  PubMed  Google Scholar 

  88. Vaysse J, Gilard V, Balayssac S, Zedde C, Martino R, Malet-Martino M. Identification of a novel sildenafil analogue in an adulterated herbal supplement. J Pharm Biomed Anal. 2012;59:58–66.

    Article  CAS  PubMed  Google Scholar 

  89. Jankovics P, Lohner S, Darcsi A, Németh-Palotás J, Béni S. Detection and structure elucidation of hydroxythiovardenafil as an adulterant in a herbal dietary supplement. J Pharm Biomed Anal. 2013;74:83–91.

    Article  CAS  PubMed  Google Scholar 

  90. Lee E-S, Kim JW, Lee JH, Han KM, Cho S, Hwang I, et al. Identification of a new tadalafil analogue found in a dietary supplement. Food Addit Contam: Part A. 2013;30(4):621–6.

    Article  CAS  Google Scholar 

  91. Lee E-S, Lee JH, Han KM, Kim JW, Hwang IS, Cho S, et al. Simultaneous determination of 38 phosphodiesterase-5 inhibitors in illicit erectile dysfunction products by liquid chromatography–electrospray ionization-tandem mass spectrometry. J Pharm Biomed Anal. 2013;83:171–8.

    Article  CAS  PubMed  Google Scholar 

  92. Lebel P, Gagnon J, Furtos A, Waldron KC. A rapid, quantitative liquid chromatography-mass spectrometry screening method for 71 active and 11 natural erectile dysfunction ingredients present in potentially adulterated or counterfeit products. J Chromatogr A. 2014;1343:143–51.

    Article  CAS  PubMed  Google Scholar 

  93. Damiano F, Silva C, Gregori A, Vacondio F, Mor M, Menozzi M, et al. Analysis of illicit dietary supplements sold in the Italian market: identification of a sildenafil thioderivative as adulterant using UPLC–TOF/MS and GC/MS. Sci Justice. 2014;54(3):228–37.

    Article  PubMed  Google Scholar 

  94. Thailand Narcotics Control Division. Table of controlled narcotic drugs in Thailand. 2015. http://narcotic.fda.moph.go.th/welcome/wp-content/uploads/2015/10/NARCO-list-update-05.10.2015.pdf. Accessed 10 May 2016.

  95. Adulyadej B. Narcotics Act. Thailand Narcotics Control Division. 1979. http://narcotic.fda.moph.go.th/english/wp-content/uploads/2012/11/Narcotics-Act-B.E.2522.pdf. Accessed 10 May 2016.

  96. House Enrolled Act No. 1196. In: Second Regular Session 117th General Assembly. 2012. http://www.in.gov/legislative/bills/2012/HE/HE1196.1.html. Accessed 10 May 2016.

  97. Beavers M. Senate Bill 48. General Assembly of the State of Tennessee. 2013. http://www.capitol.tn.gov/Bills/108/Bill/SB0048.pdf. Accessed 10 May 2016.

  98. Vermont Department of Health. Regulated Drug Rule. 2016. http://healthvermont.gov/regs/documents/regulated_drugs_rule.pdf. Accessed 10 May 2016.

  99. Louisiana State Legislature. RS 40:989.3. 2012. https://legis.la.gov/legis/Law.aspx?d=814206. Accessed 10 May 2016.

  100. Uniform Controlled Substances Act. Wisconsin State Legislature. 2016. http://docs.legis.wisconsin.gov/statutes/statutes/961/II/14. Accessed 10 May 2016.

  101. House File 2355 [Internet]. [cited 2016 May 10]. Available from: http://coolice.legis.iowa.gov/linc/85/external/HF2355_Introduced.html.

  102. Kratom Control Act. Illinois General Assembly. 2015. http://www.ilga.gov/legislation/ilcs/ilcs3.asp?ActID=3573&ChapterID=53. Accessed 10 May 2016.

  103. U.S. Food and Drug Administration. Import Alert 54–15. 2016. http://www.accessdata.fda.gov/cms_ia/importalert_1137.html. Accessed 10 May 2016.

  104. U.S. Food and Drug Administration. New Dietary Ingredients Notification Process. 2016. http://www.fda.gov/Food/DietarySupplements/NewDietaryIngredientsNotificationProcess/default.htm. Accessed 10 May 2016.

  105. United States Government Publishing Office. 21- Food and Drugs §§ 342. https://www.gpo.gov/fdsys/pkg/USCODE-2010-title21/pdf/USCODE-2010-title21-chap9-subchapIV-sec342.pdf. Accessed 19 May 2016.

  106. U.S. Food and Drug Administration. US Marshals Seize Dietary Supplements Containing Kratom. 2016. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm480344.htm. Accessed 10 May 2016.

  107. U.S. Department of Justice Drug Enforcement Administration. Drugs of Abuse. 2015. http://www.dea.gov/pr/multimedia-library/publications/drug_of_abuse.pdf#page=84. Accessed 10 May 2016.

  108. Yoburn BC, Shah S, Chan K, Duttaroy A, Davis T. Supersensitivity to opioid analgesics following chronic opioid antagonist treatment: relationship to receptor selectivity. Pharmacol Biochem Behav. 1995;51(2–3):535–9.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Medical Toxicology, Department of Emergency Medicine, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA, 01655, USA

    Alicia G. Lydecker, Kavita M. Babu & Edward W. Boyer

  2. Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, 104A Faser Hall, P.O. Box 1848, University, MS, 38677-1848, USA

    Abhisheak Sharma & Bonnie A. Avery

  3. Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, 417 Faser Hall, P.O. Box 1848, University, MS, 38677-1848, USA

    Christopher R. McCurdy & Bonnie A. Avery

Authors
  1. Alicia G. Lydecker
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  2. Abhisheak Sharma
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  3. Christopher R. McCurdy
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  4. Bonnie A. Avery
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  5. Kavita M. Babu
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  6. Edward W. Boyer
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Corresponding author

Correspondence to Alicia G. Lydecker.

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Conflict of Interest

Authors AL, AS, CM, and BA declare that they have no conflict of interest. Authors KB and EB provide medico-legal consultation and receive royalties from UpToDate. Author EB also participates in an NIH-funded research on drugs of abuse.

Sources of Funding

This study was funded by the Center of Research Excellence in Natural Products Neuroscience (CORE-NPN), Grant Number P20GM104932, which is funded by the National Institute of General Medical Sciences (NIGMS) at the National Institutes of Health (NIH) as one of its Centers of Biomedical Research Excellence (COBRE).

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Lydecker, A.G., Sharma, A., McCurdy, C.R. et al. Suspected Adulteration of Commercial Kratom Products with 7-Hydroxymitragynine. J. Med. Toxicol. 12, 341–349 (2016). https://doi.org/10.1007/s13181-016-0588-y

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  • DOI: https://doi.org/10.1007/s13181-016-0588-y

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