Acute, Sublethal, and Developmental Toxicity of Kratom ( Mitragyna speciosa Korth.) Leaf Preparations on Caenorhabditis elegans as an Invertebrate Model for Human Exposure

Samantha Hughes, David van de Klashorst, Charles A. Veltri and Oliver Grundmann
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Samantha Hughes: A-LIFE Amsterdam Institute for Life and Environment, Section Environmental Health and Toxicology, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
David van de Klashorst: HAN BioCentre, HAN University of Applied Sciences, 6525 EM Nijmegen, The Netherlands
Charles A. Veltri: Department of Pharmaceutical Sciences, College of Pharmacy, Midwestern University, Glendale, AZ 85308, USA
Oliver Grundmann: Department of Pharmaceutical Sciences, College of Pharmacy, Midwestern University, Glendale, AZ 85308, USA

IJERPH, 2022, vol. 19, issue 10, 1-19

Abstract: Kratom ( Mitragyna speciosa Korth.) is a tree native to Southeast Asia with stimulant and opioid-like effects which has seen increased use in Europe and North America in recent years. Its safety and pharmacological effects remain under investigation, especially in regard to developmental and generational toxicity. In the current study, we investigated commercial kratom preparations using the nematode Caenorhabditis elegans as a translational model for toxicity and pharmacological effects. The pure alkaloids mitragynine and 7-hydroxymitragynine as well as aqueous, ethanolic, and methanolic extracts of three commercial kratom products were evaluated using a battery of developmental, genotoxic, and opioid-related experiments. As determined previously, the mitragynine and 7-hydroxymitragynine content in kratom samples was higher in the alcoholic extracts than the aqueous extracts. Above the human consumption range equivalent of 15–70 µg/mL, kratom dose-dependently reduced brood size and health of parent worms and their progeny. 7-hydroxymitragynine, but not mitragynine, presented with toxic and developmental effects at very high concentrations, while the positive control, morphine, displayed toxic effects at 0.5 mM. Kratom and its alkaloids did not affect pumping rate or interpump interval in the same way as morphine, suggesting that kratom is unlikely to act primarily via the opioid-signalling pathway. Only at very high doses did kratom cause developmental and genotoxic effects in nematodes, indicating its relative safety.

Keywords: opioid; toxicity; pharyngeal pumping; body bending; reproduction (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2022
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