An exploratory study of the safety profile and neurocognitive function after single doses of mitragynine in humans

Abstract

Rationale: Despite the growing scientific interest on mitragynine, the primary alkaloid in kratom (Mitragyna Speciosa), there is a lack of clinical trials in humans.

Objectives: This phase 1 study aimed to evaluate mitragynine's safety profile and acute effects on subjective drug experience, neurocognition, and pain tolerance.

Methods: A placebo-controlled, single-blind, within-subjects study was conducted in two parts. In part A, eight healthy human volunteers received placebo and three doses of mitragynine (5, 10, and 20 mg) in a sequential dosing scheme, on separate days. In part B, a second group of seven volunteers received placebo and 40 mg of mitragynine. Vital signs, subjective drug experience, neurocognitive function, and pain tolerance were measured at regular intervals for 7 h after administration.

Results: Overall, mitragynine did not affect most of the outcome measures at any dose. Yet, the lowest dose (5 mg) of mitragynine increased subjective ratings of arousal and attention, accuracy in a sustained attention task, and motor inhibition. The highest dose (40 mg) of mitragynine increased subjective ratings of amnesia and produced mild psychopathological symptoms. Mitragynine did not significantly affect vital signs, and only mild, transient side effects were reported.

Conclusion: The present study suggests that low doses (5-10 mg) of mitragynine may cause subjective feelings of stimulation and enhance attention, while the highest dose (40 mg) may cause inhibitory feelings of amnesia and distress. Mitragynine doses up to 40 mg were well tolerated in this group.

Keywords: Mitragyna speciosa; Acute effects; Kratom; Mitragynine; Neurocognition; Pain; Placebo-controlled study; Safety.

Fig. 1

Mean (SE) for Systolic Blood Pressure (A), Diastolic Blood Pressure (B), Heart Rate (C), and Respiratory Rate (D) measured at the baseline and regular intervals after drug administration in both parts of the study

Fig. 2

Mean (SE) values for (BSI) Obsession-Compulsion subscale (A), CADSS amnesia (B), ARCI Amphetamine and Morphine Benzedrine Group (C) scales as a function of treatment and time after administration in both parts of the study. The ARCI ratings were taken at 1 h after drug. BSI: Brief Symptoms Inventory; CADSS: Clinician-Administered Dissociative State Scale; ARCI: Addiction Research Center Inventory

Fig. 3

Mean (SE) values for PVT (A), DSST (B), and SCWT (C) as a function of time after drug administration in both parts of the study. PVT: Psychomotor Vigilance Task; DSST: Digit-Symbol Substitution Task; SCWT: Stroop Color and Word Test

Fig. 4

Mean (SE) values for MFFT, SST, and PMT as a function of time after drug administration in both parts of the study. MMFT and SST were conducted at 1 h after drug administration. The PMT was conducted at 2 h after drug. MMFT: Matching Familiar Figures Test; SST: Stop-Signal Task; PMT: Prospective Memory Task

Fig. 5

Mean (SD) of mitragynine and 7-OH-mitragynine concentrations at baseline and at 1, 3, and 7 h after administration. Due to technical issues, data from Group B was missing