Effects of Kratom and Mitragynine

"In our study, mitragynine doses between 10 and 40 mg caused a slight decrease in blood pressure and respiratory rate. These variations were within the normal range, and therefore not considered clinically relevant. Such findings contrast with cardiorespiratory toxicities described in the literature (Brogdon et al. 2022; Sheikh et al. 2021) and cardiological alterations, including sinus tachycardia (Leong Abdullah et al. 2021), prolonged QTc interval (Leong Bin Abdullah and Singh 2021), and increased blood pressure/pulse rate in regular kratom users after drinking kratom tea containing up to 20 mg of mitragynine (Trakulsrichai et al. 2015). This suggests that the cardiovascular effects of mitragynine might be different in chronic kratom users who use higher doses or products containing other substances/contaminants, often considered responsible for health hazards. At the same time, lab safety data (clinical chemistry, hematology, and urinalysis) in the present study did not show significant deviations from normal ranges. These results are in line with findings showing that kratom did not cause alterations in blood exams of kratom users (La-Up et al. 2021, 2022; Ramachandram and Sangarran Chia Siang 2023; Singh et al. 2018; Vicknasingam et al. 2020). Further, no significant adverse events were described and only mild, transient side effects (e.g., dizziness, headache, sleepiness) were reported from participants which were related to the highest (40 mg) dose of mitragynine. In the literature (Cinosi et al. 2015; Grundmann 2017; Grundmann et al. 2023; Kruegel and Grundmann 2018), these adverse events have been reported and are often linked to chronic use. However, they did not have any clinical relevance and resolved spontaneously without treatment.

"We also found that the lowest dose (5 mg) of mitragynine increased subjective ratings of amphetamine-like arousal, subjective feelings of attention, improved accuracy in a sustained attention task and decreased inhibition in the stop signal task. Additionally, amphetamine-like arousal was also increased by mitragynine 10 mg. Such findings would suggest that low doses of mitragynine exert stimulant effects. Further, mitragynine might increase euphoria, as shown by the ratings in the Morphine Benzedrine Group scale, and selectively ameliorate cognitive performance. Increments in euphoria as assessed with the ARCI rating scale have been reported before in daily kratom users (Smith et al. 2024b). Taken together, these results suggest that mitragynine might induce some stimulatory effects on attention and arousal, supporting some previous claims that kratom products can enhance cognition (Cinosi et al. 2015; Prevete et al. 2021; Swogger et al. 2022). These data are also in line with reports from kratom users claiming that kratom does not cause cognitive impairment (Singh et al. 2019b).

"Mitragynine also exhibited stimulant effects at higher doses, as a single dose of 40 mg also led to an increase in subjective ratings of impulsivity symptoms. However, the 40 mg dose of mitragynine also increased subjective ratings of amnesia and symptoms of obsessive-compulsive behaviour, suggesting a potential sedative effect on cognition and a potential to induce symptoms of psychological distress. Overall, the stimulant and inhibitory effects of mitragynine shown in our study support earlier claims of kratom’s double action, which has been described as psychostimulant at low doses, and sedative at high doses (Kruegel and Grundmann 2018; Prozialeck et al. 2012; Singh et al. 2019b; Swogger et al. 2022) or both (Peran et al. 2023; Smith et al. 2023a)."