Effects of mitragynine on morphine and methamphetamine addiction in animal models of addiction

Abstract

Kratom (Mitragyna speciosa Korth) has long been used in folklore medicine in Southeast Asian countries. It has been used for its analgesic effects and treatment of opioid withdrawal. Mitragynine is a major alkaloid found in the leaves of kratom plant that exerts its effects via activation of opioid receptors and other receptors in the central nervous system. This study aimed to provide evaluation of abuse liability and potential of mitragynine in the treatment for opioids and amphetamine type stimulants addictions. Abuse liability of mitragynine and its effects on morphine and methamphetamine addiction were evaluated by drug discrimination, conditioned place preference and naloxone precipitated withdrawal models in rodents. Mitragynine substituted methamphetamine in drug discrimination model. It also induced conditioned place preference at high doses. Acute mitragynine withdrawal precipitated by naloxone showed significant repeated jumping behavior in both acute and chronic withdrawal. Straub tail reaction was observable in mitragynine treated group the same as in morphine-treated group. Mitragynine attenuated acquisition and expression of morphine conditioned place preference. When given with morphine, mitragynine reduced jumping behavior and Straub tail reaction. Pretreatment of mitragynine weakened methamphetamine discrimination and attenuated methamphetamine induced conditioned place preference. In conclusions, mitragynine had low abuse liability, when compared with morphine and methamphetamine, and could attenuate rewarding effect of morphine and methamphetamine. These results support not only the use of kratom in traditional medicine and self-medication in the treatment for opioid addiction and withdrawal but also in methamphetamine addiction.