Mitragynine reduced morphine-induced conditioned place preference and withdrawal in rodents

Abstract

Introduction: Kratom (Mitragyna speciosa Korth) has been long used in folklore medicine in Southeast Asian countries for its analgesic effects and the treatment of opioid withdrawal. Mitragynine is a major alkaloid found in the leaves of kratom plant that is responsible for most of the kratom pharmacological effects. It exerts its effects through the activation of opioid receptors and other receptors in the central nervous system. This study aimed to provide an evaluation of abuse liability and potential of mitragynine in the treatment for opioid addictions. Materials and Methods: Abuse liability of mitragynine was evaluated using drug discrimination and conditioned place preference models in rats, and naloxone precipitated withdrawal model in mice. The effects of mitragynine on acquisition and expression of morphine conditioned place preference were performed in rats. Naloxone-precipitated withdrawal was performed in mice treated with morphine. Results and Conclusions: Mitragynine fully substituted methamphetamine in a drug discrimination model at 10 mg/kg. It also induced conditioned place preference at doses of 30 and 90 mg/kg. Acute withdrawal symptoms precipitated by naloxone by means of repeated jumping were significant in 60 mg/kg mitragynine treated group. Straub tail reaction was observable in dose-dependent from 10 mg/kg mitragynine. In chronic withdrawal, repeated jumping behavior of mitragynine was significant at 30 mg/kg. Straub tail reaction was found in both 10 and 30 mg/kg mitragynine treated group. Mitragynine attenuated acquisition and expression of morphine conditioned place preference in dose-dependent manner from 10 to 30 mg/kg. When given with morphine, 10 mg/kg mitragynine could reduce jumping behavior to the same level as a chronic treatment of 10 mg/kg mitragynine alone and 30 mg/kg mitragynine could reduce straub tail reaction. This study indicates that mitragynine had low abuse liability and could attenuate the acquisition and expression of morphine-induced conditioned place preference and precipitated withdrawal symptoms. These results support the use of kratom in traditional medicine and self-medication for opioid addiction and withdrawal.