A Pilot, Dose-Finding, Pharmacodynamic and Pharmacokinetic Study of Orally Administered Botanical Kratom

Kratom ( Mitragyna speciosa ) is a plant indigenous to Southeast Asia. This pilot study evaluated the pharmacodynamic (PD) effects, safety, and pharmacokinetics (PK) of kratom and several of its alkaloids.

Recreational polydrug users (8 participants/cohort; 6 active: 2 placebo, N=40) completed the study. Participants had experience with opioids but were otherwise healthy. This study utilized a double-blind, between-subjects design where participants randomly received a single dose of placebo or kratom. The kratom used in the study had alkaloid levels representative of botanical kratom products (i.e., leaf) previously characterized in the literature and contained trace levels of 7-hydroxymitragynine (7-OH). The starting dose was 1 g and doses of 3, 8, 10, and 12 g were administered after safety reviews after each dose. After dosing, pupillometry and assessments of subjective effects were performed, and blood samples were collected. Safety assessments included adverse events (AE) monitoring, laboratory tests, vital signs, ECG assessments, physical examination findings, and assessment of suicidality.

No deaths or serious adverse events (SAEs) occurred. Somnolence, vomiting, and nausea were the most common AEs reported. Kratom alkaloid concentrations showed generally orderly, dose-related effects. At doses ≥3 g, kratom produced pupillary constriction. Few dose-related effects were observed, although the 12 g dose of kratom produced increases on several subjective measures including ratings of "drug liking."

This study investigated the safety of single-sourced botanical kratom; the results may not be representative of other kratom-containing products. Kratom produced some opioid-like effects including pupillary constriction, and the 12 g dose produced effects commonly associated with drugs of abuse such as visual analog scale (VAS) ratings of drug liking, good effects, and high.