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Shortly after gastrulation, molecular cues including fibroblast growth factor (FGF) signaling originating from the mesendoderm and the hindbrain instruct the preplacodal field surrounding the neural plate to form a patch of Pax2 -expressing ectoderm, which constitutes the otic-epibranchial placodes (Noramly and Grainger, 2002

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A consistent pattern emerges: evidence is mostly limited to animal studies human studies, where they exist, are small and short-term there are no high-quality trials reflecting real-world use, including combinations, higher doses or long-term administration

Instead, using kratom could lead to dependency and withdrawal symptoms of its own