Beneficial and adverse health effects of kratom (Mitragyna speciosa): A critical review of the literature

Used in Southeast Asia for generations, kratom gained popularity in the United States and elsewhere over the past several decades. Derived from Mitragyna speciosa, kratom preparations including leaves, teas, powders, capsules, and extracts may yield stimulant, analgesic, and opioid-like effects that occur dose-dependently based on concentrations of kratom's key alkaloids, mitragynine and 7-hydroxymitragynine. Such effects are responsible for kratom's potential as a reduced-harm alternative to opiates and as a withdrawal treatment. But these properties are also associated with tolerance development and addictive potential. Given mitragynine and 7-hydroxymitragynine activity on cytochrome P450 isoforms and opioid receptors, adverse effects among polysubstance users are a concern. Current literature on the toxicology of kratom is reviewed, including product alkaloid concentrations, in vitro and in vivo data, epidemiological evidence, and human case data. The potential harms and benefits of kratom products are discussed within an exposure assessment framework, and recommendations for industry are presented. Current evidence indicates that kratom may have therapeutic potential in some persons and that products present few risks with typical, non-polysubstance use. However, few studies identified alkaloid doses at which adverse effects were expected in humans or animals. Such research is needed to inform future assessments of kratom's risks and benefits. •Kratom (Mitragyna speciosa) use continues to increase in the United States.•Toxicological and pharmacological data show kratom's potential benefits and harms.•Alkaloid concentration-informed risk assessments showed few hazards with most uses.•Product concentrations of mitragynine and 7-hydroxymitragynine vary considerably.•Improved quality control would benefit U.S. kratom processors and distributors.