EFSA Compendium of Botanicals

Draft - work in progress

Mitragyna speciosa (Korth. ) Havil.

Family:: Rubiaceae
Approval state:: Approved
Number of articles retrieved:: 409
Number of processed references:: 11

Compositions

#1: Mitragynine in leaves #2: alkaloid extract in leaves #3: 7-hydroxymitragynine in dried leaves #4: Mitragynine in dried leaves #5: ajmalicine in leaves #6: corynantheidine, isomitraphylline, mitraphylline, paynantheine, isocorynantheidine in leaves #7: 7-hydroxymitragynine in leaves #8: mitragynine in leaves #9: quinovic acid 3-O-beta-D-quinovopyranoside and quinovic acid 3-O-beta-D-glucopyranoside in leaves #10: Mitragynine in leaves #11: Epigallocatechin in leaves #12: formic acid in leaves #13: Mitragynine in leaves #14: gallic acid in leaves #15: Mitragynine in stems #16: Secologanin in leaves #17: Secologanin in roots #18: Secologanin in stems #19: 7-hydroxymitragynine in leaves #20: rhynchophylline percentage of the total alkaloids in leaves #21: Mitragynine in leaves #22: paynantheine percentage of the total alkaloids in leaves #23: speciociliatine and speciogynine percentage of the total alkaloids in leaves #24: mitraphylline percentage of the total alkaloids in leaves #25: mitralactonal percentage of the total alkaloids in leaves #26: mitragynaline percentage of the total alkaloids in leaves #27: raubasine percentage of the total alkaloids in leaves #28: Speciogynine in leaves #29: Mitragynine in leaves #30: corynoxine A / B in leaves #31: 7-hydroxymitragynine in leaves #32: Paynantheine in leaves #33: Speciociliatine in leaves

Endpoint Studies

#1: 14-21 gram of leaves powder intake are potentially associated to withdrawal. Withdrawal symptoms were reported 2 days past exposure cessation (fever and chills, slight abdominal discomfort which developed into intense abdominal pain on day 8 and concomitant brown discoloration of the urine. Noticeable jaundice and pruritus, insomnia and restlessness) #2: Changes in behaviour #3: Blood pressure #4: Body weight measurement #5: Liver damage #6: Piloerection was observed at the intermediate (10mg/kg) and high doses (100mg/kg) during the last week of treatment #7: Mild ptosis was distinguishable in groups treated with a daily dose of 100 mg/kg mitragynine #8: After the 3rd week of treatment, both male and female animals treated with 100 mg / kg daily dose of mitragynine showed aggressive behaviors #9: female group treated with (100mg/kg) demonstrated a significant decrease in relative body weight (RBW) compared to the control group after 2weeks of daily administration. #10: Signs of liver toxicity after prolonged exposure to the higher dose (sub-chronic 28days:100mg/kg) (histopathological, hematological and biochemical effects). #11: Signs of brain toxicity after prolonged exposure to the higher dose (sub-chronic 28days:100mg/kg) (histopathological, hematological and biochemical effects). #12: Signs of kidney toxicity after prolonged exposure to the higher dose (sub-chronic 28days:100mg/kg) (histopathological, hematological and biochemical effects). #13: Liver weight showed a significant increase in animals treated with high dose (100mg/kg) in both male and female groups. #14: Cardiac adverse events in humans from leaf powder #15: neurological adverse events in humans from leaf powder #16: gastrointestinal adverse events in humans from leaf powder #17: musculoskeletal adverse events in humans from leaf powder #18: other adverse events in humans from leaf powder #19: Mitragynine level in blood in case of a lethal intoxication #20: Mitragynine level in urine in case of lethal intoxication #21: 7-hydroxymitragynine level in blood in case of a lethal intoxication #22: 7-hydroxymitragynine level in urine in case of lethal intoxication

Genotoxicity

#1: The induced DNA damage in Caco-2 (HTB-37) is not likely to be caused by Mitragynine itself but rather by other unknown substances present in the products or by interactions among those compounds.

Composition #1: Kong Wai Mun., Chik Zamri., Mohamed Zahurin., Alshawsh Mohammed A. Physicochemical Characterization of Mitragyna speciosa Alkaloid Extract and Mitragynine Using In Vitro High Throughput Assays. combinatorial chemistry & high throughput screening, 2017, p. Combinatorial chemistry & high throughput screening (2017). .

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Methanol Chloroform
Substance:

mitragynine (RF-00003500-PAR)
Analytical method code:

High Performance Liquid Chromatography (HPLC)/Liquid Chromatography (LC) (F018A)
Result unit:

Microgram/millilitre (G052A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Numerical Value (VAL)
Value (concentration, content):

0.4
Internal remarks:

Mitragynine in leaves

Composition #2: Kong Wai Mun., Chik Zamri., Mohamed Zahurin., Alshawsh Mohammed A. Physicochemical Characterization of Mitragyna speciosa Alkaloid Extract and Mitragynine Using In Vitro High Throughput Assays. combinatorial chemistry & high throughput screening, 2017, p. Combinatorial chemistry & high throughput screening (2017). .

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Methanol Chloroform
Substance:

Alkaloids (RF-00004360-PAR)
Analytical method code:

High Performance Liquid Chromatography (HPLC)/Liquid Chromatography (LC) (F018A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

alkaloid extract in leaves

Composition #3: Kikura-Hanajiri, Ruri., Kawamura, Maiko., Maruyama, Takuro., Kitajima, Mariko., Takayama, Hiromitsu., Goda, Yukihiro. Simultaneous analysis of mitragynine, 7-hydroxymitragynine, and other alkaloids in the psychotropic plant "kratom" (Mitragyna speciosa) by LC-ESI-MS . forensic toxicology, 2009, vol. 27, no. 2, p. 67–74. DOI: 10.1007/s11419-009-0070-5. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

MeOH
Substance:

7-hydroxymitragynine (RF-00004124-PAR)
Analytical method code:

Chromatographic tests (F015A)
Result unit:

Milligram/gram (G060A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

0.114 - 0.361
Internal remarks:

7-hydroxymitragynine in dried leaves

Composition #4: Kikura-Hanajiri, Ruri., Kawamura, Maiko., Maruyama, Takuro., Kitajima, Mariko., Takayama, Hiromitsu., Goda, Yukihiro. Simultaneous analysis of mitragynine, 7-hydroxymitragynine, and other alkaloids in the psychotropic plant "kratom" (Mitragyna speciosa) by LC-ESI-MS . forensic toxicology, 2009, vol. 27, no. 2, p. 67–74. DOI: 10.1007/s11419-009-0070-5. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

MeOH
Substance:

mitragynine (RF-00003500-PAR)
Analytical method code:

Chromatographic tests (F015A)
Result unit:

Milligram/gram (G060A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

0.8 - 21.2
Internal remarks:

Mitragynine in dried leaves

Composition #5: Leon, Francisco., Habib, Eman., Adkins, Jessica E., Furr, Edward B., McCurdy, Christopher R., Cutler, Stephen J. Phytochemical Characterization of the Leaves of Mitragyna speciosa Grown in USA . natural product communications, 2009, vol. 4, no. 7, p. 907–910. .

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Methanol
Substance:

Ajmalicine (RF-00003669-PAR)
Analytical method code:

Chromatographic tests (F015A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

ajmalicine in leaves

Composition #6: Leon, Francisco., Habib, Eman., Adkins, Jessica E., Furr, Edward B., McCurdy, Christopher R., Cutler, Stephen J. Phytochemical Characterization of the Leaves of Mitragyna speciosa Grown in USA . natural product communications, 2009, vol. 4, no. 7, p. 907–910. .

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Methanol
Substance:

Alkaloids (RF-00004360-PAR)
Additional substance description:

corynantheidine, isomitraphylline, mitraphylline, paynantheine, isocorynantheidine
Analytical method code:

Chromatographic tests (F015A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

corynantheidine, isomitraphylline, mitraphylline, paynantheine, isocorynantheidine in leaves

Composition #7: Leon, Francisco., Habib, Eman., Adkins, Jessica E., Furr, Edward B., McCurdy, Christopher R., Cutler, Stephen J. Phytochemical Characterization of the Leaves of Mitragyna speciosa Grown in USA . natural product communications, 2009, vol. 4, no. 7, p. 907–910. .

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Methanol
Substance:

7-hydroxymitragynine (RF-00004124-PAR)
Analytical method code:

Chromatographic tests (F015A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

7-hydroxymitragynine in leaves

Composition #8: Leon, Francisco., Habib, Eman., Adkins, Jessica E., Furr, Edward B., McCurdy, Christopher R., Cutler, Stephen J. Phytochemical Characterization of the Leaves of Mitragyna speciosa Grown in USA . natural product communications, 2009, vol. 4, no. 7, p. 907–910. .

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Methanol
Substance:

mitragynine (RF-00003500-PAR)
Analytical method code:

Chromatographic tests (F015A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

mitragynine in leaves

Composition #9: Leon, Francisco., Habib, Eman., Adkins, Jessica E., Furr, Edward B., McCurdy, Christopher R., Cutler, Stephen J. Phytochemical Characterization of the Leaves of Mitragyna speciosa Grown in USA . natural product communications, 2009, vol. 4, no. 7, p. 907–910. .

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Methanol
Substance:

Triterpene saponins Triterpene saponins (RF-00004338-PAR)
Additional substance description:

quinovic acid 3-O-beta-D-quinovopyranoside and quinovic acid 3-O-beta-D-glucopyranoside
Analytical method code:

Chromatographic tests (F015A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

quinovic acid 3-O-beta-D-quinovopyranoside and quinovic acid 3-O-beta-D-glucopyranoside in leaves

Composition #10: Harizal, S. N., Mansor, S. M., Hasnan, J., Tharakan, J. K. J., Abdullah, J. Acute toxicity study of the standardized methanolic extract of Mitragyna speciosa Korth in Rodent . journal of ethnopharmacology, 2010, vol. 131, no. 2, p. 404–409. DOI: 10.1016/j.jep.2010.07.013. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Methanol
Substance:

mitragynine (RF-00003500-PAR)
Analytical method code:

GC-MS (F046A)
Result unit:

Percent (G138A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

1.6
Internal remarks:

Mitragynine in leaves

Composition #11: Charoonratana, Tossaton., Wungsintaweekul, Juraithip., Pathompak, Pathamaporn., Georgiev, Milen I., Choi, Young Hae., Verpoorte, Robert. Limitation of Mitragynine Biosynthesis in Mitragyna speciosa (Roxb.) Korth. through Tryptamine Availability . zeitschrift fur naturforschung section c-a journal of biosciences, 2013, vol. 68, no. 9-10, p. 394–405. .

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Methanol
Substance:

Epigallocatechin (RF-00010399-PAR)
Analytical method code:

Nuclear Magnetic Resonance (NMR) and Electron Spin Resonance (ESR) spectroscopy (F060A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Epigallocatechin in leaves

Composition #12: Charoonratana, Tossaton., Wungsintaweekul, Juraithip., Pathompak, Pathamaporn., Georgiev, Milen I., Choi, Young Hae., Verpoorte, Robert. Limitation of Mitragynine Biosynthesis in Mitragyna speciosa (Roxb.) Korth. through Tryptamine Availability . zeitschrift fur naturforschung section c-a journal of biosciences, 2013, vol. 68, no. 9-10, p. 394–405. .

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Methanol
Substance:

Methanoic acid (RF-00006311-PAR)
Analytical method code:

Nuclear Magnetic Resonance (NMR) and Electron Spin Resonance (ESR) spectroscopy (F060A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

formic acid in leaves

Composition #13: Charoonratana, Tossaton., Wungsintaweekul, Juraithip., Pathompak, Pathamaporn., Georgiev, Milen I., Choi, Young Hae., Verpoorte, Robert. Limitation of Mitragynine Biosynthesis in Mitragyna speciosa (Roxb.) Korth. through Tryptamine Availability . zeitschrift fur naturforschung section c-a journal of biosciences, 2013, vol. 68, no. 9-10, p. 394–405. .

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Methanol
Substance:

mitragynine (RF-00003500-PAR)
Analytical method code:

High Performance Liquid Chromatography (HPLC)/Liquid Chromatography (LC) (F018A)
Result unit:

Milligram/gram (G060A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

3.96 - 4.01
Internal remarks:

Mitragynine in leaves

Composition #14: Charoonratana, Tossaton., Wungsintaweekul, Juraithip., Pathompak, Pathamaporn., Georgiev, Milen I., Choi, Young Hae., Verpoorte, Robert. Limitation of Mitragynine Biosynthesis in Mitragyna speciosa (Roxb.) Korth. through Tryptamine Availability . zeitschrift fur naturforschung section c-a journal of biosciences, 2013, vol. 68, no. 9-10, p. 394–405. .

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Methanol
Substance:

gallic acid (RF-00003821-PAR)
Analytical method code:

Nuclear Magnetic Resonance (NMR) and Electron Spin Resonance (ESR) spectroscopy (F060A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

gallic acid in leaves

Composition #15: Charoonratana, Tossaton., Wungsintaweekul, Juraithip., Pathompak, Pathamaporn., Georgiev, Milen I., Choi, Young Hae., Verpoorte, Robert. Limitation of Mitragynine Biosynthesis in Mitragyna speciosa (Roxb.) Korth. through Tryptamine Availability . zeitschrift fur naturforschung section c-a journal of biosciences, 2013, vol. 68, no. 9-10, p. 394–405. .

Language:

English (en)
Plant part:

Stem / stalk (as part-nature) (A067S)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Methanol
Substance:

mitragynine (RF-00003500-PAR)
Analytical method code:

High Performance Liquid Chromatography (HPLC)/Liquid Chromatography (LC) (F018A)
Result unit:

Milligram/gram (G060A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

0.78 - 1.22
Internal remarks:

Mitragynine in stems

Composition #16: Charoonratana, Tossaton., Wungsintaweekul, Juraithip., Pathompak, Pathamaporn., Georgiev, Milen I., Choi, Young Hae., Verpoorte, Robert. Limitation of Mitragynine Biosynthesis in Mitragyna speciosa (Roxb.) Korth. through Tryptamine Availability . zeitschrift fur naturforschung section c-a journal of biosciences, 2013, vol. 68, no. 9-10, p. 394–405. .

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Methanol
Substance:

Acetaldehyde (RF-00004845-PAR)
Additional substance description:

secologanin
Analytical method code:

High Performance Liquid Chromatography (HPLC)/Liquid Chromatography (LC) (F018A)
Result unit:

Milligram/gram (G060A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

9.36
Internal remarks:

Secologanin in leaves

Composition #17: Charoonratana, Tossaton., Wungsintaweekul, Juraithip., Pathompak, Pathamaporn., Georgiev, Milen I., Choi, Young Hae., Verpoorte, Robert. Limitation of Mitragynine Biosynthesis in Mitragyna speciosa (Roxb.) Korth. through Tryptamine Availability . zeitschrift fur naturforschung section c-a journal of biosciences, 2013, vol. 68, no. 9-10, p. 394–405. .

Language:

English (en)
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Methanol
Substance:

Acetaldehyde (RF-00004845-PAR)
Additional substance description:

secologanin
Analytical method code:

High Performance Liquid Chromatography (HPLC)/Liquid Chromatography (LC) (F018A)
Result unit:

Milligram/gram (G060A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

4.11
Internal remarks:

Secologanin in roots

Composition #18: Charoonratana, Tossaton., Wungsintaweekul, Juraithip., Pathompak, Pathamaporn., Georgiev, Milen I., Choi, Young Hae., Verpoorte, Robert. Limitation of Mitragynine Biosynthesis in Mitragyna speciosa (Roxb.) Korth. through Tryptamine Availability . zeitschrift fur naturforschung section c-a journal of biosciences, 2013, vol. 68, no. 9-10, p. 394–405. .

Language:

English (en)
Plant part:

Stem / stalk (as part-nature) (A067S)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Methanol
Substance:

Acetaldehyde (RF-00004845-PAR)
Additional substance description:

secologanin
Analytical method code:

High Performance Liquid Chromatography (HPLC)/Liquid Chromatography (LC) (F018A)
Result unit:

Milligram/gram (G060A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

4.11
Internal remarks:

Secologanin in stems

Composition #19: Warner, Marcus L., Kaufman, Nellie C., Grundmann, Oliver. The pharmacology and toxicology of kratom: from traditional herb to drug of abuse . international journal of legal medicine, 2016, vol. 130, no. 1, p. 127–138. DOI: 10.1007/s00414-015-1279-y. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Substance:

7-hydroxymitragynine (RF-00004124-PAR)
Analytical method code:

Unspecified (F598A)
Result unit:

Percent (G138A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

2
Internal remarks:

7-hydroxymitragynine in leaves

Composition #20: Warner, Marcus L., Kaufman, Nellie C., Grundmann, Oliver. The pharmacology and toxicology of kratom: from traditional herb to drug of abuse . international journal of legal medicine, 2016, vol. 130, no. 1, p. 127–138. DOI: 10.1007/s00414-015-1279-y. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Substance:

Alkaloids (RF-00004360-PAR)
Additional substance description:

rhynchophylline
Analytical method code:

Unspecified (F598A)
Result unit:

Percent (G138A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

<1
Internal remarks:

rhynchophylline percentage of the total alkaloids in leaves

Composition #21: Warner, Marcus L., Kaufman, Nellie C., Grundmann, Oliver. The pharmacology and toxicology of kratom: from traditional herb to drug of abuse . international journal of legal medicine, 2016, vol. 130, no. 1, p. 127–138. DOI: 10.1007/s00414-015-1279-y. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Substance:

mitragynine (RF-00003500-PAR)
Analytical method code:

Unspecified (F598A)
Result unit:

Percent (G138A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

60
Internal remarks:

Mitragynine in leaves

Composition #22: Warner, Marcus L., Kaufman, Nellie C., Grundmann, Oliver. The pharmacology and toxicology of kratom: from traditional herb to drug of abuse . international journal of legal medicine, 2016, vol. 130, no. 1, p. 127–138. DOI: 10.1007/s00414-015-1279-y. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Substance:

Alkaloids (RF-00004360-PAR)
Additional substance description:

paynantheine
Analytical method code:

Unspecified (F598A)
Result unit:

Percent (G138A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

10
Internal remarks:

paynantheine percentage of the total alkaloids in leaves

Composition #23: Warner, Marcus L., Kaufman, Nellie C., Grundmann, Oliver. The pharmacology and toxicology of kratom: from traditional herb to drug of abuse . international journal of legal medicine, 2016, vol. 130, no. 1, p. 127–138. DOI: 10.1007/s00414-015-1279-y. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Substance:

Alkaloids (RF-00004360-PAR)
Additional substance description:

speciociliatine and speciogynine
Analytical method code:

Unspecified (F598A)
Result unit:

Percent (G138A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

7-9
Internal remarks:

speciociliatine and speciogynine percentage of the total alkaloids in leaves

Composition #24: Warner, Marcus L., Kaufman, Nellie C., Grundmann, Oliver. The pharmacology and toxicology of kratom: from traditional herb to drug of abuse . international journal of legal medicine, 2016, vol. 130, no. 1, p. 127–138. DOI: 10.1007/s00414-015-1279-y. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Substance:

Alkaloids (RF-00004360-PAR)
Additional substance description:

mitraphylline
Analytical method code:

Unspecified (F598A)
Result unit:

Percent (G138A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

<1
Internal remarks:

mitraphylline percentage of the total alkaloids in leaves

Composition #25: Warner, Marcus L., Kaufman, Nellie C., Grundmann, Oliver. The pharmacology and toxicology of kratom: from traditional herb to drug of abuse . international journal of legal medicine, 2016, vol. 130, no. 1, p. 127–138. DOI: 10.1007/s00414-015-1279-y. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Substance:

Alkaloids (RF-00004360-PAR)
Additional substance description:

mitralactonal
Analytical method code:

Unspecified (F598A)
Result unit:

Percent (G138A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

<1
Internal remarks:

mitralactonal percentage of the total alkaloids in leaves

Composition #26: Warner, Marcus L., Kaufman, Nellie C., Grundmann, Oliver. The pharmacology and toxicology of kratom: from traditional herb to drug of abuse . international journal of legal medicine, 2016, vol. 130, no. 1, p. 127–138. DOI: 10.1007/s00414-015-1279-y. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Substance:

Alkaloids (RF-00004360-PAR)
Additional substance description:

mitragynaline
Analytical method code:

Unspecified (F598A)
Result unit:

Percent (G138A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

<1
Internal remarks:

mitragynaline percentage of the total alkaloids in leaves

Composition #27: Warner, Marcus L., Kaufman, Nellie C., Grundmann, Oliver. The pharmacology and toxicology of kratom: from traditional herb to drug of abuse . international journal of legal medicine, 2016, vol. 130, no. 1, p. 127–138. DOI: 10.1007/s00414-015-1279-y. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Substance:

Alkaloids (RF-00004360-PAR)
Additional substance description:

raubasine
Analytical method code:

Unspecified (F598A)
Result unit:

Percent (G138A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

<1
Internal remarks:

raubasine percentage of the total alkaloids in leaves

Composition #28: Oliveira, Ana Sofia., Fraga, Sonia., Carvalho, Felix., Araujo, Ana Margarida., Pereira, Cristiana Costa., Teixeira, Joao Paulo., Bastos, Maria de Lourdes., de Pinho, Paula Guedes. Chemical characterization and in vitro cyto- and genotoxicity of 'legal high' products containing Kratom (Mitragyna speciosa) . forensic toxicology, 2016, vol. 34, no. 2, p. 213–226. DOI: 10.1007/s11419-015-0305-6. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

CHCl3/MeOH (1:2, v/v)
Substance:

Alkaloids (RF-00004360-PAR)
Additional substance description:

Speciogynine
Analytical method code:

GC-MS (F046A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Speciogynine in leaves

Composition #29: Oliveira, Ana Sofia., Fraga, Sonia., Carvalho, Felix., Araujo, Ana Margarida., Pereira, Cristiana Costa., Teixeira, Joao Paulo., Bastos, Maria de Lourdes., de Pinho, Paula Guedes. Chemical characterization and in vitro cyto- and genotoxicity of 'legal high' products containing Kratom (Mitragyna speciosa) . forensic toxicology, 2016, vol. 34, no. 2, p. 213–226. DOI: 10.1007/s11419-015-0305-6. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

CHCl3/MeOH (1:2, v/v)
Substance:

mitragynine (RF-00003500-PAR)
Analytical method code:

GC-MS (F046A)
Result unit:

Milligram/gram (G060A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

0.64 - 3.04
Internal remarks:

Mitragynine in leaves

Composition #30: Oliveira, Ana Sofia., Fraga, Sonia., Carvalho, Felix., Araujo, Ana Margarida., Pereira, Cristiana Costa., Teixeira, Joao Paulo., Bastos, Maria de Lourdes., de Pinho, Paula Guedes. Chemical characterization and in vitro cyto- and genotoxicity of 'legal high' products containing Kratom (Mitragyna speciosa) . forensic toxicology, 2016, vol. 34, no. 2, p. 213–226. DOI: 10.1007/s11419-015-0305-6. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

CHCl3/MeOH (1:2, v/v)
Substance:

Alkaloids (RF-00004360-PAR)
Additional substance description:

corynoxine A / B
Analytical method code:

GC-MS (F046A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

corynoxine A / B in leaves

Composition #31: Oliveira, Ana Sofia., Fraga, Sonia., Carvalho, Felix., Araujo, Ana Margarida., Pereira, Cristiana Costa., Teixeira, Joao Paulo., Bastos, Maria de Lourdes., de Pinho, Paula Guedes. Chemical characterization and in vitro cyto- and genotoxicity of 'legal high' products containing Kratom (Mitragyna speciosa) . forensic toxicology, 2016, vol. 34, no. 2, p. 213–226. DOI: 10.1007/s11419-015-0305-6. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

CHCl3/MeOH (1:2, v/v)
Substance:

7-hydroxymitragynine (RF-00004124-PAR)
Analytical method code:

GC-MS (F046A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

7-hydroxymitragynine in leaves

Composition #32: Oliveira, Ana Sofia., Fraga, Sonia., Carvalho, Felix., Araujo, Ana Margarida., Pereira, Cristiana Costa., Teixeira, Joao Paulo., Bastos, Maria de Lourdes., de Pinho, Paula Guedes. Chemical characterization and in vitro cyto- and genotoxicity of 'legal high' products containing Kratom (Mitragyna speciosa) . forensic toxicology, 2016, vol. 34, no. 2, p. 213–226. DOI: 10.1007/s11419-015-0305-6. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

CHCl3/MeOH (1:2, v/v)
Substance:

Alkaloids (RF-00004360-PAR)
Additional substance description:

Paynantheine
Analytical method code:

GC-MS (F046A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Paynantheine in leaves

Composition #33: Oliveira, Ana Sofia., Fraga, Sonia., Carvalho, Felix., Araujo, Ana Margarida., Pereira, Cristiana Costa., Teixeira, Joao Paulo., Bastos, Maria de Lourdes., de Pinho, Paula Guedes. Chemical characterization and in vitro cyto- and genotoxicity of 'legal high' products containing Kratom (Mitragyna speciosa) . forensic toxicology, 2016, vol. 34, no. 2, p. 213–226. DOI: 10.1007/s11419-015-0305-6. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

CHCl3/MeOH (1:2, v/v)
Substance:

Alkaloids (RF-00004360-PAR)
Additional substance description:

Speciociliatine
Analytical method code:

GC-MS (F046A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Speciociliatine in leaves

Endpoint study #1: Kapp, Friedrich G., Maurer, Hans H., Auwarter, Volker., Winkelmann, Martin., Hermanns-Clausen, Maren. Intrahepatic cholestasis following abuse of powdered kratom (Mitragyna speciosa). . journal of medical toxicology : official journal of the american college of medical toxicology, 2011, vol. 7, no. 3, p. 227–31. DOI: 10.1007/s13181-011-0155-5. [DOI link]

Study relevance:

Human health
Substance:

mitragynine (RF-00003500-PAR)
Plant part:

Leaves (as part-nature) (A0EKT)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Type of toxicological test:

case report (CHD060TT)
Tested organism:

Human (as organism) (A056J)
Sex:

Male
Route of exposure:

ORAL: DRINKING WATER (OECD2229PL)
Exposure duration:

2.0
Unit of exposure duration:

Week (G205A)
Number of organisms dosed:

1
Control groups used:

no
Endpoint measured:

Lowest observed adverse effect level (CHD026EP)
Concentration unit:

Gram (G148A)
Effect concentration:

14 - 21
Effect description:

Withdrawal symptoms
Effect or parameter linked to the endpoint:

urinalysis (CHD029BE)
Internal remarks:

14-21 gram of leaves powder intake are potentially associated to withdrawal. Withdrawal symptoms were reported 2 days past exposure cessation (fever and chills, slight abdominal discomfort which developed into intense abdominal pain on day 8 and concomitant brown discoloration of the urine. Noticeable jaundice and pruritus, insomnia and restlessness)

Endpoint study #2: Harizal, S. N., Mansor, S. M., Hasnan, J., Tharakan, J. K. J., Abdullah, J. Acute toxicity study of the standardized methanolic extract of Mitragyna speciosa Korth in Rodent . journal of ethnopharmacology, 2010, vol. 131, no. 2, p. 404–409. DOI: 10.1016/j.jep.2010.07.013. [DOI link]

Study relevance:

Human health
Substance:

mitragynine (RF-00003500-PAR)
Plant part:

Leaves (as part-nature) (A0EKT)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

powdered leaves
Type of toxicological test:

acute toxicity (CHD016TT)
Guideline used:

Equivalent or similar to
Guideline:

OECD GUIDELINE 407 (REPEATED DOSE 28-DAY ORAL TOXICITY IN RODENTS) (OECD1255PL)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Unit of exposure duration:

single (food/feed) (G203A)
Number of organisms dosed:

48
Control groups used:

yes, concurrent vehicle
Endpoint measured:

Lowest observable effect concentration (CHD027EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

1000
Effect description:

Rats treated with 1000 mg/kg Mitragyna specios a extract showed very low level of activity (slow movement) and rapid breathing which lasted 30min after drug administration. (use of 2 guidelines: OECD guideline nos.420(OECD, 2001) and407(OECD, 1995).
Effect or parameter linked to the endpoint:

behaviour (CHD001BE)
Internal remarks:

Changes in behaviour

Endpoint study #3: Harizal, S. N., Mansor, S. M., Hasnan, J., Tharakan, J. K. J., Abdullah, J. Acute toxicity study of the standardized methanolic extract of Mitragyna speciosa Korth in Rodent . journal of ethnopharmacology, 2010, vol. 131, no. 2, p. 404–409. DOI: 10.1016/j.jep.2010.07.013. [DOI link]

Study relevance:

Human health
Substance:

mitragynine (RF-00003500-PAR)
Plant part:

Leaves (as part-nature) (A0EKT)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

powdered leaves
Type of toxicological test:

acute toxicity (CHD016TT)
Guideline used:

Equivalent or similar to
Guideline:

OECD GUIDELINE 407 (REPEATED DOSE 28-DAY ORAL TOXICITY IN RODENTS) (OECD1255PL)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Unit of exposure duration:

single (food/feed) (G203A)
Number of organisms dosed:

48
Control groups used:

yes, concurrent vehicle
Endpoint measured:

Lowest observable effect concentration (CHD027EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

100
Critical effect:

HEMOPOIETIC (TOX10A)
Effect description:

All groups of Mitragyna speciosa extract exhibit significantly high blood pressure for both systolic and diastolic compared to negative control group and morphine group. (use of 2 guidelines: OECD guideline nos.420(OECD, 2001) and407(OECD, 1995).
Effect or parameter linked to the endpoint:

haematology (CHD023BE)
Internal remarks:

Blood pressure

Endpoint study #4: Harizal, S. N., Mansor, S. M., Hasnan, J., Tharakan, J. K. J., Abdullah, J. Acute toxicity study of the standardized methanolic extract of Mitragyna speciosa Korth in Rodent . journal of ethnopharmacology, 2010, vol. 131, no. 2, p. 404–409. DOI: 10.1016/j.jep.2010.07.013. [DOI link]

Study relevance:

Human health
Substance:

mitragynine (RF-00003500-PAR)
Plant part:

Leaves (as part-nature) (A0EKT)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

powdered leaves
Type of toxicological test:

acute toxicity (CHD016TT)
Guideline used:

Equivalent or similar to
Guideline:

OECD GUIDELINE 407 (REPEATED DOSE 28-DAY ORAL TOXICITY IN RODENTS) (OECD1255PL)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Unit of exposure duration:

single (food/feed) (G203A)
Number of organisms dosed:

48
Control groups used:

yes, concurrent vehicle
Endpoint measured:

Lowest observable effect concentration (CHD027EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

100
Effect description:

CMC (negative control) group showed the highest increase in body weight compared to the other four rat groups administered with morphine and Mitragyna speciosa extract (use of 2 guidelines: OECD guideline nos.420(OECD, 2001) and407(OECD, 1995).
Effect or parameter linked to the endpoint:

food consumption (CHD007BE)
Internal remarks:

Body weight measurement

Endpoint study #5: Harizal, S. N., Mansor, S. M., Hasnan, J., Tharakan, J. K. J., Abdullah, J. Acute toxicity study of the standardized methanolic extract of Mitragyna speciosa Korth in Rodent . journal of ethnopharmacology, 2010, vol. 131, no. 2, p. 404–409. DOI: 10.1016/j.jep.2010.07.013. [DOI link]

Study relevance:

Human health
Substance:

mitragynine (RF-00003500-PAR)
Plant part:

Leaves (as part-nature) (A0EKT)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

powdered leaves
Type of toxicological test:

acute toxicity (CHD016TT)
Guideline used:

Equivalent or similar to
Guideline:

OECD GUIDELINE 407 (REPEATED DOSE 28-DAY ORAL TOXICITY IN RODENTS) (OECD1255PL)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Unit of exposure duration:

single (food/feed) (G203A)
Number of organisms dosed:

48
Control groups used:

yes, concurrent vehicle
Endpoint measured:

Lowest observable effect concentration (CHD027EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

1000
Target tissue:

digestive: Liver (TT023A)
Effect description:

Mitragyna speciosa extract at 1000mg/kg caused a significant damage in liver (use of 2 guidelines: OECD guideline nos.420(OECD, 2001) and407(OECD, 1995).
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

Liver damage

Endpoint study #6: Sabetghadam, Azadeh., Ramanathan, Surash., Sasidharan, Sreenivasan., Mansor, Sharif Mahsufi. Subchronic exposure to mitragynine, the principal alkaloid of Mitragyna speciosa, in rats . journal of ethnopharmacology, 2013, vol. 146, no. 3, p. 815–823. DOI: 10.1016/j.jep.2013.02.008. [DOI link]

Study relevance:

Human health
Substance:

mitragynine (RF-00003500-PAR)
Plant part:

Leaves (as part-nature) (A0EKT)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Type of toxicological test:

short-term toxicity (CHD017TT)
Limit test:

Yes
Guideline used:

According to
Guideline:

OECD GUIDELINE 407 (REPEATED DOSE 28-DAY ORAL TOXICITY IN RODENTS) (OECD1255PL)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male/Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

28.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

56
Control groups used:

yes, concurrent vehicle
Endpoint measured:

Lowest observed adverse effect level (CHD026EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

10
Critical effect:

SYSTEMIC (TOX01A)
Target tissue:

Skin/subcutis (TT056A)
Effect description:

Piloerection
Effect or parameter linked to the endpoint:

other (CHD003BE)
Internal remarks:

Piloerection was observed at the intermediate (10mg/kg) and high doses (100mg/kg) during the last week of treatment

Endpoint study #7: Sabetghadam, Azadeh., Ramanathan, Surash., Sasidharan, Sreenivasan., Mansor, Sharif Mahsufi. Subchronic exposure to mitragynine, the principal alkaloid of Mitragyna speciosa, in rats . journal of ethnopharmacology, 2013, vol. 146, no. 3, p. 815–823. DOI: 10.1016/j.jep.2013.02.008. [DOI link]

Study relevance:

Human health
Substance:

mitragynine (RF-00003500-PAR)
Plant part:

Leaves (as part-nature) (A0EKT)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Type of toxicological test:

short-term toxicity (CHD017TT)
Limit test:

Yes
Guideline used:

According to
Guideline:

OECD GUIDELINE 407 (REPEATED DOSE 28-DAY ORAL TOXICITY IN RODENTS) (OECD1255PL)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male/Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

28.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

56
Control groups used:

yes, concurrent vehicle
Endpoint measured:

Lowest observed adverse effect level (CHD026EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

100
Critical effect:

SYSTEMIC (TOX01A)
Target tissue:

Skin/subcutis (TT056A)
Effect description:

Mild ptosis
Effect or parameter linked to the endpoint:

morphology (CHD013BE)
Internal remarks:

Mild ptosis was distinguishable in groups treated with a daily dose of 100 mg/kg mitragynine

Endpoint study #8: Sabetghadam, Azadeh., Ramanathan, Surash., Sasidharan, Sreenivasan., Mansor, Sharif Mahsufi. Subchronic exposure to mitragynine, the principal alkaloid of Mitragyna speciosa, in rats . journal of ethnopharmacology, 2013, vol. 146, no. 3, p. 815–823. DOI: 10.1016/j.jep.2013.02.008. [DOI link]

Study relevance:

Human health
Substance:

mitragynine (RF-00003500-PAR)
Plant part:

Leaves (as part-nature) (A0EKT)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Type of toxicological test:

short-term toxicity (CHD017TT)
Limit test:

Yes
Guideline used:

According to
Guideline:

OECD GUIDELINE 407 (REPEATED DOSE 28-DAY ORAL TOXICITY IN RODENTS) (OECD1255PL)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male/Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

28.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

56
Control groups used:

yes, concurrent vehicle
Endpoint measured:

Lowest observed adverse effect level (CHD026EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

100
Critical effect:

SYSTEMIC (TOX01A)
Target tissue:

neurologic: Central Nervous System (TT035A)
Effect description:

Aggressive behaviors
Effect or parameter linked to the endpoint:

behaviour (CHD001BE)
Internal remarks:

After the 3rd week of treatment, both male and female animals treated with 100 mg / kg daily dose of mitragynine showed aggressive behaviors

Endpoint study #9: Sabetghadam, Azadeh., Ramanathan, Surash., Sasidharan, Sreenivasan., Mansor, Sharif Mahsufi. Subchronic exposure to mitragynine, the principal alkaloid of Mitragyna speciosa, in rats . journal of ethnopharmacology, 2013, vol. 146, no. 3, p. 815–823. DOI: 10.1016/j.jep.2013.02.008. [DOI link]

Study relevance:

Human health
Substance:

mitragynine (RF-00003500-PAR)
Plant part:

Leaves (as part-nature) (A0EKT)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Type of toxicological test:

short-term toxicity (CHD017TT)
Limit test:

Yes
Guideline used:

According to
Guideline:

OECD GUIDELINE 407 (REPEATED DOSE 28-DAY ORAL TOXICITY IN RODENTS) (OECD1255PL)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male/Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

28.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

56
Control groups used:

yes, concurrent vehicle
Endpoint measured:

Lowest observed adverse effect level (CHD026EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

100
Critical effect:

DEVELOPMENTAL (TOX07A)
Target tissue:

Digestive (TT002A)
Effect description:

Relative Body Weight (RBW)
Effect or parameter linked to the endpoint:

organ weights (CHD012BE)
Internal remarks:

female group treated with (100mg/kg) demonstrated a significant decrease in relative body weight (RBW) compared to the control group after 2weeks of daily administration.

Endpoint study #10: Sabetghadam, Azadeh., Ramanathan, Surash., Sasidharan, Sreenivasan., Mansor, Sharif Mahsufi. Subchronic exposure to mitragynine, the principal alkaloid of Mitragyna speciosa, in rats . journal of ethnopharmacology, 2013, vol. 146, no. 3, p. 815–823. DOI: 10.1016/j.jep.2013.02.008. [DOI link]

Study relevance:

Human health
Substance:

mitragynine (RF-00003500-PAR)
Plant part:

Leaves (as part-nature) (A0EKT)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Type of toxicological test:

short-term toxicity (CHD017TT)
Limit test:

Yes
Guideline used:

According to
Guideline:

OECD GUIDELINE 407 (REPEATED DOSE 28-DAY ORAL TOXICITY IN RODENTS) (OECD1255PL)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male/Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

28.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

56
Control groups used:

yes, concurrent vehicle
Endpoint measured:

Lowest observed adverse effect level (CHD026EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

100
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

histopathological effects
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

Signs of liver toxicity after prolonged exposure to the higher dose (sub-chronic 28days:100mg/kg) (histopathological, hematological and biochemical effects).

Endpoint study #11: Sabetghadam, Azadeh., Ramanathan, Surash., Sasidharan, Sreenivasan., Mansor, Sharif Mahsufi. Subchronic exposure to mitragynine, the principal alkaloid of Mitragyna speciosa, in rats . journal of ethnopharmacology, 2013, vol. 146, no. 3, p. 815–823. DOI: 10.1016/j.jep.2013.02.008. [DOI link]

Study relevance:

Human health
Substance:

mitragynine (RF-00003500-PAR)
Plant part:

Leaves (as part-nature) (A0EKT)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Type of toxicological test:

short-term toxicity (CHD017TT)
Limit test:

Yes
Guideline used:

According to
Guideline:

OECD GUIDELINE 407 (REPEATED DOSE 28-DAY ORAL TOXICITY IN RODENTS) (OECD1255PL)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male/Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

28.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

56
Control groups used:

yes, concurrent vehicle
Endpoint measured:

Lowest observed adverse effect level (CHD026EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

100
Critical effect:

NEUROTOXICITY (TOX04A)
Target tissue:

neurologic: Brain (TT034A)
Effect description:

histopathological effects
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

Signs of brain toxicity after prolonged exposure to the higher dose (sub-chronic 28days:100mg/kg) (histopathological, hematological and biochemical effects).

Endpoint study #12: Sabetghadam, Azadeh., Ramanathan, Surash., Sasidharan, Sreenivasan., Mansor, Sharif Mahsufi. Subchronic exposure to mitragynine, the principal alkaloid of Mitragyna speciosa, in rats . journal of ethnopharmacology, 2013, vol. 146, no. 3, p. 815–823. DOI: 10.1016/j.jep.2013.02.008. [DOI link]

Study relevance:

Human health
Substance:

mitragynine (RF-00003500-PAR)
Plant part:

Leaves (as part-nature) (A0EKT)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Type of toxicological test:

short-term toxicity (CHD017TT)
Limit test:

Yes
Guideline used:

According to
Guideline:

OECD GUIDELINE 407 (REPEATED DOSE 28-DAY ORAL TOXICITY IN RODENTS) (OECD1255PL)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male/Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

28.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

56
Control groups used:

yes, concurrent vehicle
Endpoint measured:

Lowest observed adverse effect level (CHD026EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

100
Critical effect:

NEPHROTOXICITY (TOX03A)
Target tissue:

urogenital: Kidneys (TT046A)
Effect description:

histopathological effects
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

Signs of kidney toxicity after prolonged exposure to the higher dose (sub-chronic 28days:100mg/kg) (histopathological, hematological and biochemical effects).

Endpoint study #13: Sabetghadam, Azadeh., Ramanathan, Surash., Sasidharan, Sreenivasan., Mansor, Sharif Mahsufi. Subchronic exposure to mitragynine, the principal alkaloid of Mitragyna speciosa, in rats . journal of ethnopharmacology, 2013, vol. 146, no. 3, p. 815–823. DOI: 10.1016/j.jep.2013.02.008. [DOI link]

Study relevance:

Human health
Substance:

mitragynine (RF-00003500-PAR)
Plant part:

Leaves (as part-nature) (A0EKT)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Type of toxicological test:

short-term toxicity (CHD017TT)
Limit test:

Yes
Guideline used:

According to
Guideline:

OECD GUIDELINE 407 (REPEATED DOSE 28-DAY ORAL TOXICITY IN RODENTS) (OECD1255PL)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male/Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

28.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

56
Control groups used:

yes, concurrent vehicle
Endpoint measured:

Lowest observed adverse effect level (CHD026EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

100
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

Liver weight
Effect or parameter linked to the endpoint:

organ weights (CHD012BE)
Internal remarks:

Liver weight showed a significant increase in animals treated with high dose (100mg/kg) in both male and female groups.

Endpoint study #14: Trakulsrichai, Satariya., Tongpo, Achara., Sriapha, Charuwan., Wongvisawakorn, Sunun., Rittilert, Panee., Kaojarern, Sming., Wananukul, Winai. Kratom Abuse in Ramathibodi Poison Center, Thailand: A Five-Year Experience . journal of psychoactive drugs, 2013, vol. 45, no. 5, p. 404–408. DOI: 10.1080/02791072.2013.844532. [DOI link]

Study relevance:

Human health
Plant part:

Leaves (as part-nature) (A0EKT)
Additional plant/substance description:

leaf powder
Type of toxicological test:

acute toxicity (CHD016TT)
Limit test:

No
Tested organism:

Human (as organism) (A056J)
Sex:

Male/Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Number of organisms dosed:

52
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

PULMONARY AND CARDIAC (TOX08A)
Effect description:

Palpitation, high blood pressure, syncope, hypotension
Effect or parameter linked to the endpoint:

not reported (CHD030BE)
Internal remarks:

Cardiac adverse events in humans from leaf powder

Endpoint study #15: Trakulsrichai, Satariya., Tongpo, Achara., Sriapha, Charuwan., Wongvisawakorn, Sunun., Rittilert, Panee., Kaojarern, Sming., Wananukul, Winai. Kratom Abuse in Ramathibodi Poison Center, Thailand: A Five-Year Experience . journal of psychoactive drugs, 2013, vol. 45, no. 5, p. 404–408. DOI: 10.1080/02791072.2013.844532. [DOI link]

Study relevance:

Human health
Plant part:

Leaves (as part-nature) (A0EKT)
Additional plant/substance description:

leaf powder
Type of toxicological test:

acute toxicity (CHD016TT)
Limit test:

No
Tested organism:

Human (as organism) (A056J)
Sex:

Male/Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Number of organisms dosed:

52
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

NEUROTOXICITY (TOX04A)
Target tissue:

Neurologic (TT004A)
Effect description:

seizure, alteration of consciousness, confusion, headache, dizziness, insomnia, tremor, agitation, contraction, dystonia
Effect or parameter linked to the endpoint:

neurology (CHD027BE)
Internal remarks:

neurological adverse events in humans from leaf powder

Endpoint study #16: Trakulsrichai, Satariya., Tongpo, Achara., Sriapha, Charuwan., Wongvisawakorn, Sunun., Rittilert, Panee., Kaojarern, Sming., Wananukul, Winai. Kratom Abuse in Ramathibodi Poison Center, Thailand: A Five-Year Experience . journal of psychoactive drugs, 2013, vol. 45, no. 5, p. 404–408. DOI: 10.1080/02791072.2013.844532. [DOI link]

Study relevance:

Human health
Plant part:

Leaves (as part-nature) (A0EKT)
Additional plant/substance description:

leaf powder
Type of toxicological test:

acute toxicity (CHD016TT)
Limit test:

No
Tested organism:

Human (as organism) (A056J)
Sex:

Male/Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Number of organisms dosed:

52
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

Digestive (TOX18A)
Target tissue:

Digestive (TT002A)
Effect description:

Abdominal pain, diarrhea, loss of appetite
Effect or parameter linked to the endpoint:

not reported (CHD030BE)
Internal remarks:

gastrointestinal adverse events in humans from leaf powder

Endpoint study #17: Trakulsrichai, Satariya., Tongpo, Achara., Sriapha, Charuwan., Wongvisawakorn, Sunun., Rittilert, Panee., Kaojarern, Sming., Wananukul, Winai. Kratom Abuse in Ramathibodi Poison Center, Thailand: A Five-Year Experience . journal of psychoactive drugs, 2013, vol. 45, no. 5, p. 404–408. DOI: 10.1080/02791072.2013.844532. [DOI link]

Study relevance:

Human health
Plant part:

Leaves (as part-nature) (A0EKT)
Additional plant/substance description:

leaf powder
Type of toxicological test:

acute toxicity (CHD016TT)
Limit test:

No
Tested organism:

Human (as organism) (A056J)
Sex:

Male/Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Number of organisms dosed:

52
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

MUSCLO-SKELETAL (TOX13A)
Target tissue:

Muscle, Skeletal (TT055A)
Effect description:

Ataxia, myalgia, non specific chest pain, chest discomfort, fatigue, contraction
Effect or parameter linked to the endpoint:

not reported (CHD030BE)
Internal remarks:

musculoskeletal adverse events in humans from leaf powder

Endpoint study #18: Trakulsrichai, Satariya., Tongpo, Achara., Sriapha, Charuwan., Wongvisawakorn, Sunun., Rittilert, Panee., Kaojarern, Sming., Wananukul, Winai. Kratom Abuse in Ramathibodi Poison Center, Thailand: A Five-Year Experience . journal of psychoactive drugs, 2013, vol. 45, no. 5, p. 404–408. DOI: 10.1080/02791072.2013.844532. [DOI link]

Study relevance:

Human health
Plant part:

Leaves (as part-nature) (A0EKT)
Additional plant/substance description:

leaf powder
Type of toxicological test:

acute toxicity (CHD016TT)
Limit test:

No
Tested organism:

Human (as organism) (A056J)
Sex:

Male/Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Number of organisms dosed:

52
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

Other toxicities (TOX19A)
Effect description:

dry mouth, diaphoresis
Effect or parameter linked to the endpoint:

other (CHD003BE)
Internal remarks:

other adverse events in humans from leaf powder

Endpoint study #19: Karinen, Ritva., Fosen, Jan Toralf., Rogde, Sidsel., Vindenes, Vigdis. An accidental poisoning with mitragynine. forensic science international, 2014, vol. 245, p. E29–E32. DOI: 10.1016/j.forsciint.2014.10.025. [DOI link]

Study relevance:

Human health
Substance:

mitragynine (RF-00003500-PAR)
Plant part:

Unspecified (A07XD)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Yes
Tested organism:

Human (as organism) (A056J)
Sex:

Male
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Number of organisms dosed:

1
Control groups used:

no
Endpoint measured:

Amount of drug required to induce mortality (CHD076EP)
Concentration unit:

Milligram-equivalent/litre (G160A)
Effect concentration:

1.06
Critical effect:

PULMONARY AND CARDIAC (TOX08A)
Target tissue:

respiratory: Lung (TT041A)
Effect description:

mortality
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

Mitragynine level in blood in case of a lethal intoxication

Endpoint study #20: Karinen, Ritva., Fosen, Jan Toralf., Rogde, Sidsel., Vindenes, Vigdis. An accidental poisoning with mitragynine. forensic science international, 2014, vol. 245, p. E29–E32. DOI: 10.1016/j.forsciint.2014.10.025. [DOI link]

Study relevance:

Human health
Substance:

mitragynine (RF-00003500-PAR)
Plant part:

Unspecified (A07XD)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Yes
Tested organism:

Human (as organism) (A056J)
Sex:

Male
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Number of organisms dosed:

1
Control groups used:

no
Endpoint measured:

Amount of drug required to induce mortality (CHD076EP)
Concentration unit:

Milligram-equivalent/litre (G160A)
Effect concentration:

3.47
Critical effect:

PULMONARY AND CARDIAC (TOX08A)
Target tissue:

respiratory: Lung (TT041A)
Effect description:

mortality
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

Mitragynine level in urine in case of lethal intoxication

Endpoint study #21: Karinen, Ritva., Fosen, Jan Toralf., Rogde, Sidsel., Vindenes, Vigdis. An accidental poisoning with mitragynine. forensic science international, 2014, vol. 245, p. E29–E32. DOI: 10.1016/j.forsciint.2014.10.025. [DOI link]

Study relevance:

Human health
Substance:

7-hydroxymitragynine (RF-00004124-PAR)
Plant part:

Unspecified (A07XD)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Yes
Tested organism:

Human (as organism) (A056J)
Sex:

Male
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Number of organisms dosed:

1
Control groups used:

no
Endpoint measured:

Amount of drug required to induce mortality (CHD076EP)
Concentration unit:

Milligram-equivalent/litre (G160A)
Effect concentration:

0.15
Critical effect:

PULMONARY AND CARDIAC (TOX08A)
Target tissue:

respiratory: Lung (TT041A)
Effect description:

mortality
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

7-hydroxymitragynine level in blood in case of a lethal intoxication

Endpoint study #22: Karinen, Ritva., Fosen, Jan Toralf., Rogde, Sidsel., Vindenes, Vigdis. An accidental poisoning with mitragynine. forensic science international, 2014, vol. 245, p. E29–E32. DOI: 10.1016/j.forsciint.2014.10.025. [DOI link]

Study relevance:

Human health
Substance:

7-hydroxymitragynine (RF-00004124-PAR)
Plant part:

Unspecified (A07XD)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Yes
Tested organism:

Human (as organism) (A056J)
Sex:

Male
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Number of organisms dosed:

1
Control groups used:

no
Endpoint measured:

Amount of drug required to induce mortality (CHD076EP)
Concentration unit:

Milligram-equivalent/litre (G160A)
Effect concentration:

2.20
Critical effect:

PULMONARY AND CARDIAC (TOX08A)
Target tissue:

respiratory: Lung (TT041A)
Effect description:

mortality
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

7-hydroxymitragynine level in urine in case of lethal intoxication

Genotox #1: Oliveira, Ana Sofia., Fraga, Sonia., Carvalho, Felix., Araujo, Ana Margarida., Pereira, Cristiana Costa., Teixeira, Joao Paulo., Bastos, Maria de Lourdes., de Pinho, Paula Guedes. Chemical characterization and in vitro cyto- and genotoxicity of 'legal high' products containing Kratom (Mitragyna speciosa) . forensic toxicology, 2016, vol. 34, no. 2, p. 213–226. DOI: 10.1007/s11419-015-0305-6. [DOI link]

Study category:

Genotoxicity
Type of toxicological test:

DNA damage and repair assay, unscheduled DNA synthesis in mammalian cells in vitro (CHD038TT)
Method type:

in vitro
Tested organism:

Other (A07XE)
Sex:

No data
Control groups used:

yes
Endpoint measured:

DNA damage and/or repair
Is genotoxic:

Positive
Remarks on genotox study:

Comet assay analysis of DNA damage in Caco-2 cells exposed to the pure MG standard and Kratom sample extracts for 24 h
Internal remarks:

The induced DNA damage in Caco-2 (HTB-37) is not likely to be caused by Mitragynine itself but rather by other unknown substances present in the products or by interactions among those compounds.
Internal ID:

WOS:000379164800002