Kratom (Mitragyna speciosa) alkaloids influence on cardiopulmonary measures and high-fat diet-induced weight gain in mice

Kratom (Mitragyna speciosa) has been marketed and used for a variety of health-promoting applications. Kratom contains an expansive bioactive alkaloid profile with mitragynine (MTG) as the most abundant. Individual responses to kratom have been reported, but the role of obesity as a factor influencing the effects of kratom has not been studied. First, we used a standardized kratom extract (KE) to determine the cardiopulmonary differences with KE (290, 500 mg/kg) and matched MTG (18 mg/kg) in high-fat diet (HFD; 45% Fat) induced obese male C57Bl/6 J mice. As measured by whole-body plethysmography, acute oral dosing revealed an approximate 15% reduction in the respiratory rate with all doses of KE and MTG. Unlike a well-known respiratory depressant, alprazolam, KE and MTG did not reduce minute ventilation (MvB; ml/min). As measured by volume-pressure recordings, KE 500 mg/kg produced an approximate 12% reduction in heart rate in normal weight mice. Second, we determined whether daily oral dosing KE (50, 150 mg/kg) prevented HFD-induced weight gain. Daily 150 mg/kg resulted in an increase in body weight gain (∼1 g) in the last week after 21 days of dosing. After 4 days following kratom cessation, there was reduced distance traveled in the KE 150 mg/kg compared with the KE 50 mg/kg group in an elevated plus maze test. These findings demonstrate a dose-dependent-increase in weight gain with KE, suggesting further investigation is needed to delineate kratom alkaloid effects on metabolism and body weight control.