Use and Effects of Kratom

"Kratom leaves are typically crushed, smoked, brewed in tea, or eaten [41]. The half-life of mitragynine is around 3.5 hours. The onset of effects of kratom alkaloids is about 10-20 minutes, with peak effects occurring around two to four hours after ingestion [4]. The clinical effects of kratom can vary by dose, producing stimulant-like effects at lower doses and opioid-like effects at higher doses [53,54].

"The kratom alkaloids are primarily metabolized hepatically by cytochrome P450 enzymes through linear pharmacokinetics and have a biphasic elimination pattern [55,56]. Mitragynine is metabolized to the more active form 7-OH-mitragynine through four CYP 450 isoenzymes: 2C19, 3A4, 2D6, and 2C18 [56-58]. The CYP3A4-mediated dehydrogenation process is believed to activate mitragynine, not the trace concentrations of 7-OH-mitragynine found in kratom extracts that lead to its analgesic effects [40].

"Kratom use is associated with various toxicities and organ dysfunction through studies on cell lines and animal models [43,59]. Studies have found evidence of cardiotoxic and cytotoxic effects of mitragynine and its diastereomers [47,60]. Indole alkaloids have also been shown to inhibit CYP450 isoforms (including CYP3A4 and CYP2D6), resulting in drug-drug interactions with CYP450-mediated compounds [61,62]. Studies also showed that the kratom alkaloids have activity against glutathione transferases, including UGT1A1 and UGT2B7, suggesting interactions with other UGT substrate drugs [63-65]. These interactions can contribute to various presentations associated with kratom toxicity in the form of the airway, antipsychotic toxicities, and organ injury [41]."