A systematic review of (pre)clinical studies on the therapeutic potential and safety profile of kratom in humans

Introduction: Kratom (Mitragyna speciosa) is a tropical plant traditionally used as an ethnomedicinal remedy for several conditions in South East Asia. Despite the increased interest in its therapeutical benefits in Western countries, little scientific evidence is available to support such claims, and existing data remain limited to kratom's chronic consumption. Objective: Our study aims to investigate (pre)clinical evidence on the efficacy of kratom as a therapeutic aid and its safety profile in humans. Methods: A systematic literature search using PubMed and the Medline database was conducted between April and November 2020. Results: Both preclinical (N = 57) and clinical (N = 18) studies emerged from our search. Preclinical data indicated a therapeutic value in terms of acute/chronic pain (N = 23), morphine/ethanol withdrawal, and dependence (N = 14), among other medical conditions (N = 26). Clinical data included interventional studies (N = 2) reporting reduced pain sensitivity, and observational studies (N = 9) describing the association between kratom's chronic (daily/frequent) use and safety issues, in terms of health consequences (e.g., learning impairment, high cholesterol level, dependence/withdrawal). Conclusions: Although the initial (pre)clinical evidence on kratom's therapeutic potential and its safety profile in humans is encouraging, further validation in large, controlled clinical trials is required.