Comprehensive Literature Search

A search was conducted with PubMed and Embase using a search strategy encompassing terms involving “kratom” and its related synonyms, as well as terms to capture pharmacokinetic herb-drug interactions, specific enzymes and transporters. Study types included in the search were case studies, clinical trials, and in vitro studies and mechanistic studies; reviews, studies in animals, and studies examining pharmacodynamic effects were excluded. The search returned 56 unique results (31 Pubmed studies and 37 Embase studies including duplicates), and titles and abstracts were screened for possible relevance by at least two independent reviewers. After initial screening, 15 total full text articles were obtained and screened to ensure relevance to the study by two independent clinically trained reviewers, working either as a team or independently. Any disagreements relating to article selection were resolved by discussion. Finally, 8 total studies were selected for entry into the repository and were subsequently reviewed for quality assurance.