Kratom and Mitragynine

"Over the past decade, kratom use has become increasingly popular in the United States (US). Many thousands of US users have reported that consumption of kratom preparations (most often in the form of dried, powdered leaf material) is an efficacious treatment not only for physical pain, but also for mood and anxiety disorders, particularly in cases where other available treatments have either failed or elicited intolerable side effects.9−13 A significant portion of users have also reported use of kratom as a tool to stop or reduce consumption of prescription or illicit opioids, a potential application that is presently of high interest given the ongoing opioid abuse epidemic in the US. Unfortunately, there have been no controlled clinical studies either examining these alleged therapeutic effects or quantifying any potential risks of kratom use. At the same time, kratom is primarily distributed through unregulated Internet sales and used outside medical supervision. Considering these factors, as well as the reported opioid-like effects and adverse health effects of the plant, the US Drug Enforcement Administration (DEA) and the US Food and Drug Administration (FDA) have both raised concerns that kratom represents a potential drug of abuse and public health threat.14−16 In September 2016, the DEA announced its intent to place the active compounds found in kratom into Schedule I of the Controlled Substances Act but ultimately decided not to proceed with this action following a large public outcry from the kratom user community, including over 23 000 comments logged in the federal register docket for this issue.13,17−19 Despite this turn of events, kratom at this time remains in regulatory limbo, with an uncertain future in the US. Accordingly, our laboratories have been working to develop a preclinical profile of kratom’s biological effects, with the hope that such knowledge will prove useful for the development of future therapeutics based on kratom, as well as guide regulatory decision making on the plant itself.

"Kratom contains a number of indole alkaloids that are believed to be the primary contributors to its psychoactive effects. Chief among these is mitragynine (Figure 1), which typically constitutes 1–2% of the dry leaf mass and up to approximately two-thirds of the total alkaloid content.1,5 This compound is joined by 7-hydroxymitragynine (7-OH, Figure 1) in much lower concentrations, typically less than 0.05% of the dried leaf mass.1,20 The other predominant alkaloids found in kratom leaf are speciogynine, speciociliatine, and paynantheine (each ∼0.2–0.5% of dry leaf mass), but at this time little is known about their pharmacology.1,5"