Comparative Toxicity Assessment of Kratom Decoction, Mitragynine and Speciociliatine Versus Morphine on Zebrafish (Danio rerio) Embryos

Background: Kratom (Mitragyna speciosa Korth), a popular opioid-like plant holds its therapeutic potential in pain management and opioid dependence. However, there are growing concerns about the safety or potential toxicity risk of kratom after prolonged use. Aim of the study: The study aimed to assess the possible toxic effects of kratom decoction and its major alkaloids, mitragynine, and speciociliatine in comparison to morphine in an embryonic zebrafish model. Methods: The zebrafish embryos were exposed to kratom decoction (1,000-62.5 μg/ml), mitragynine, speciociliatine, and morphine (100-3.125 μg/ml) for 96 h post-fertilization (hpf). The toxicity parameters, namely mortality, hatching rate, heart rate, and morphological malformations were examined at 24, 48, 72, and 96 hpf, respectively. Results: Kratom decoction at a concentration range of ≥500 μg/ml caused 100% mortality of zebrafish embryos and decreased the hatching rate in a concentration-dependent manner. Meanwhile, mitragynine and speciociliatine exposure resulted in 100% mortality of zebrafish embryos at 100 μg/ml. Both alkaloids caused significant alterations in the morphological development of zebrafish embryos including hatching inhibition and spinal curvature (scoliosis) at the highest concentration. While exposure to morphine induced significant morphological malformations such as pericardial oedema, spinal curvature (lordosis), and yolk edema in zebrafish embryos. Conclusion: Our findings provide evidence for embryonic developmental toxicity of kratom decoction and its alkaloids both mitragynine and speciociliatine at the highest concentration, hence suggesting that kratom consumption may have potential teratogenicity risk during pregnancy and thereby warrants further investigations.