AIM OF STUDY: To investigate the effect of mitragynine after chronic morphine treatment on cyclic AMP (cAMP) level and mRNA expression of mu-opioid receptor (MOR) in human neuroblastoma SK-N-SH cell.
METHOD AND MATERIALS: Mitragynine was isolated from the Mitragyna speciosa plant using the acid-base extraction method. The cAMP level upon forskolin stimulation in the cells was determined using the Calbiochem(®) Direct Immunoassay Kit. The mRNA expression of the MOR was carried out using quantitative RT-PCR.
RESULT: Cotreatment and pretreatment of morphine and mitragynine significantly reduced the production of cAMP level at a lower concentration of mitragynine while the higher concentration of this compound could lead to the development of tolerance and dependence as shown by the increase of the cAMP level production in foskolin stimulation. In MOR mRNA expression study, cotreatment of morphine with mitragynine significantly reduced the down-regulation of MOR mRNA expression as compared to morphine treatment only.
CONCLUSION: These finding suggest that mitragynine could possibly avoid the tolerance and dependence on chronic morphine treatment by reducing the up-regulation of cAMP level as well as reducing the down-regulation of MOR at a lower concentration of mitragynine.
AIMS: In the present study, we investigated the effects of mitragynine on spatial learning and synaptic transmission in the CA1 region of the hippocampus.
METHODS: Male Sprague Dawley rats received daily (for 12 days) training sessions in the Morris water maze, with each session followed by treatment either with mitragynine (1, 5, or 10 mg/kg; intraperitoneally), morphine (5 mg/kg; intraperitoneally) or a vehicle. In the second experiment, we recorded field excitatory postsynaptic potentials in the hippocampal CA1 area in anesthetized rats and assessed the effects of mitragynine on baseline synaptic transmission, paired-pulse facilitation, and long-term potentiation. Gene expression of major memory- and addiction-related genes was investigated and the effects of mitragynine on Ca2+ influx was also examined in cultured primary neurons from E16-E18 rats.
RESULTS/OUTCOMES: Escape latency results indicate that animals treated with mitragynine displayed a slower rate of acquisition as compared to their control counterparts. Further, mitragynine treatment significantly reduced the amplitude of baseline (i.e. non-potentiated) field excitatory postsynaptic potentials and resulted in a minor suppression of long-term potentiation in CA1. Bdnf and αCaMKII mRNA expressions in the brain were not affected and Ca2+ influx elicited by glutamate application was inhibited in neurons pre-treated with mitragynine.
CONCLUSIONS/INTERPRETATION: These data suggest that high doses of mitragynine (5 and 10 mg/kg) cause memory deficits, possibly via inhibition of Ca2+ influx and disruption of hippocampal synaptic transmission and long-term potentiation induction.
MATERIALS AND METHODS: Male and female Sprague-Dawley rats received three doses of mitragynine (1, 10, 100mg/kg, p.o) for 28 days respectively. Food intake and relative body weight were measured during the experiment. After completion of drug treatment biochemical, hematological, and histological analyses were performed.
RESULTS: No mortality was observed in any of the treatment groups. The groups of rats treated with the lower and intermediate doses showed no toxic effects during the study. However, the relative body weight of the group of female rats treated with the 100mg/kg dose was decreased significantly. Food intake also tended to decrease in the same group. Only relative liver weight increased after treatment with the high dose of mitragynine (100mg/ kg) in both the male and female treatment groups of rats. Biochemical and hematological parameters were also altered especially in high dose treatment group which corresponds to the histopathological changes.
CONCLUSIONS: The study demonstrated that mitragynine is relatively safe at lower sub-chronic doses (1-10mg/kg) but exhibited toxicity at a highest dose (sub-chronic 28 days: 100mg/kg). This was confirmed by liver, kidney, and brain histopathological changes, as well as hematological and biochemical changes.
AIM OF THE STUDY: To evaluate kratom's effects towards hematological and clinical-chemistry parameters among regular kratom users in Malaysia.
METHODS: A total of 77 subjects (n=58 regular kratom users, and n=19 healthy controls) participated in this cross-sectional study. All the surveys were conducted through face-to-face interview to elicit subject's socio-demographic characteristics and kratom use history. A full-blood test was also administered. Laboratory analysis was conducted using GC-MS to determine mitragynine content in the acquired kratom samples in order to relate mitragynine consumption with possible alterations in the blood parameters of kratom users.
RESULTS: Findings showed that there were no significant differences in the hematological and clinical-chemistry parameters of traditional kratom users and healthy controls, except for HDL and LDL cholesterol values; these were found to be above the normal reference range for the former. Similarly, long-term kratom consumption (>5 years), and quantity of daily kratom use (≥3 ½ glasses; mitragynine content 76.3-114.8mg) did not appear to alter the hematological and biochemical parameters of kratom users.
CONCLUSION: These data suggest that even long-term and heavy kratom consumption did not significantly alter the hematological and clinical-chemistry parameters of kratom users in a traditional setting.