Mitragyna speciosa, commonly known as kratom, is indigenous to Southeast Asia. The leaves have been used in traditional medicine to treat pain, fatigue, fever, diarrhea, and wounds ⁽¹⁾, while its extracts are known for their psychoactive properties, especially morphine-like effects ⁽²⁾. Kratom has gained popularity as a supplement to improve mood, and decrease anxiety and pain. It has also been a source of significant controversy. The FDA has issued numerous statements against kratom, citing adverse events, potentially related deaths, risk of addiction or overdose, and incidences of contaminated supplements ^{(3) (4) (5)}.

Kratom has both stimulant and sedative properties ⁽⁶⁾. The main psychoactive constituents are mitragynine and 7-hydroxymitragynine ⁽⁷⁾. In vivo studies of derivative compounds and analogs from kratom demonstrate antinociceptive effects ⁽⁸⁾. Animal models suggest that kratom has muscle relaxant ⁽⁹⁾, anti-inflammatory ⁽¹⁰⁾, analgesic ⁽¹¹⁾, and anorectic ⁽¹²⁾ properties. Mitragynine has also shown antioxidant and antiproliferative effects in a few cancer cell lines ⁽¹³⁾.

Data on the use and safety of kratom in humans are very limited. Stimulant effects occur at lower doses, while sedative and pain-relieving effects occur at higher doses ⁽¹⁴⁾. Kratom users may develop physiological dependence and experience withdrawal ⁽¹⁵⁾, but this risk has not yet been adequately quantified ⁽¹⁶⁾. More research on the therapeutic uses for kratom and its constituents, as well as its toxic effects and abuse potential is needed.

The biological activities of kratom in humans are still poorly characterized ⁽¹⁷⁾. Because of its potential interactions with other drugs ^(18) (19) and possible side effects ⁽²⁰⁾, kratom should not be used as a substitute for prescription pain medications. Several countries and US states have banned the use of kratom due to its potential for abuse ^(21) (22).