Abstract
Parallel to the growing use of kratom, there is a wealth of evidence from self-report, preclinical, and early clinical studies on therapeutic benefits of its alkaloids in particular for treating pain, managing substance use disorder, and coping with emotional or mental health conditions. On the other hand, there are also reports on potential health risks concerning kratom use. These two aspects are often discussed in reviews on kratom. Here, we aim to highlight specific areas that are of importance to give insights into the mechanistic of kratom alkaloids pharmacological actions. This includes their interactions with drug-metabolizing enzymes and predictions of clinical drug-drug interactions, receptor-binding properties, interactions with cellular barriers in regards to barrier permeability, involvement of membrane transporters, and alteration of barrier function when exposed to the alkaloids.
Highlights
Kratom (Mitragyna speciosa Korth.) use in the traditional settings in Southeast Asian countries Malaysia and Thailand to treat minor ailments and to increase work endurance among manual laborers is not new
We have gathered and discussed physiological interactions of kratom alkaloids within the scope of interactions with drug-metabolizing enzymes and potential for drug-drug interactions, interactions with central nervous system receptors to relate with pharmacological actions, and interactions with cellular barriers of which are not limited to mechanisms of barrier permeability, and effects of exposure to kratom alkaloids on the barrier function
The interactions with enzymes and the receptors may not be necessarily new in regards to kratom research, these areas have gained renewed interest among researchers in recent years due to the wealth of evidence on pharmacological actions of the alkaloids in preclinical studies, the rise of kratom use for self-treatment purposes, and the controversies surrounding the consumption of kratom
Summary
Kratom (Mitragyna speciosa Korth.) use in the traditional settings in Southeast Asian countries Malaysia and Thailand to treat minor ailments and to increase work endurance among manual laborers is not new. Findings from preclinical studies, for example, antinociceptive activity to some extent corroborated with data from self-report studies of which among the reasons for kratom use is to manage pain, further supported by the recent randomized controlled study in humans (Vicknasingam et al, 2020). This seems to be the case for use of kratom to alleviate opioid withdrawal (Hassan et al, 2020) and to relieve anxiety
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