The Impact of Diverse Kratom Products on Use Patterns, Dependence, and Toxicity

Kratom products have been available in the US for over a decade. Initially, these products were almost entirely made from kratom leaf material and formulated in powders, capsules, or tablets. Recently, more diverse kratom products and derivatives have been marketed and sold, including extracts, concentrates, and isolates. This review focuses on the differing symptom presentation of products containing concentrated or isolated kratom-derived alkaloids that may cause substantial risks to consumers.

Recently, several concentrated or semi-synthetic products have entered the market that are advertised as kratom, but which pharmacologically bear little similarity to traditional kratom. Although the alkaloid content naturally ranges from 2 to 5% in native leaf material, it can be up to 60% in concentrated extracts. Most concerning are the products containing pure, isolated 7-hydroxymitragynine and mitragynine pseudoindoxyl. These derivatives of kratom alkaloids are not naturally present in leaf material, but function as more potent opioid agonists than morphine. Products marketed as kratom but containing much higher alkaloid concentrations than found in the natural kratom leaf, or semi-synthetic isolates of highly potent alkaloid derivatives not typically found in the plant, represent a growing public health concern. There is minimal clinical research to assess their safety or regulation to ensure safe manufacturing practices. Limited pre-clinical data indicate that these products pose a greater risk of toxicity, drug interactions, and physiologic dependence. And based on misleading advertising, consumers may be unaware of the differences and increased risks associated with these products compared with traditional whole leaf kratom.