Abstract
BackgroundOpiate addiction is a major health problem in many countries. A crucial component of the medical treatment is the management of highly aversive opiate withdrawal signs, which may otherwise lead to resumption of drug taking. In a medication-assisted treatment (MAT), methadone and buprenorphine have been implemented as substitution drugs. Despite MAT effectiveness, there are still limitations and side effects of using methadone and buprenorphine. Thus, other alternative therapies with less side effects, overdosing, and co-morbidities are desired. One of the potential pharmacotherapies may involve kratom's major indole alkaloid, mitragynine, since kratom (Mitragyna speciosa Korth.) preparations have been reported to alleviate opiate withdrawal signs in self-treatment in Malaysian opiate addicts.MethodsBased on the morphine withdrawal model, rats were morphine treated with increasing doses from 10 to 50 mg/kg twice daily over a period of 6 days. The treatment was discontinued on day 7 in order to induce a spontaneous morphine abstinence. The withdrawal signs were measured daily after 24 h of the last morphine administration over a period of 28 abstinence days. In rats that developed withdrawal signs, a drug replacement treatment was given using mitragynine, methadone, or buprenorphine and the global withdrawal score was evaluated.ResultsThe morphine withdrawal model induced profound withdrawal signs for 16 days. Mitragynine (5–30 mg/kg; i.p.) was able to attenuate acute withdrawal signs in morphine dependent rats. On the other hand, smaller doses of methadone (0.5–2 mg/kg; i.p.) and buprenorphine (0.4–1.6 mg/kg; i.p.) were necessary to mitigate these effects.ConclusionsThese data suggest that mitragynine may be a potential drug candidate for opiate withdrawal treatment.
Highlights
Abuse and addiction to opioids including prescription pain relievers, heroin, and synthetic opioids such as fentanyl caused a serious national crisis in the United States (US), that affects public health as well as social and economic welfare [1]
Smaller doses of methadone (0.5–2 mg/kg; i.p.) and buprenorphine (0.4–1.6 mg/kg; i.p.) were necessary to mitigate these effects. These data suggest that mitragynine may be a potential drug candidate for opiate withdrawal treatment
We further evaluated the effects of mitragynine on morphinewithdrawal induced changes in hematological, biochemical, and histopathological parameters
Summary
Abuse and addiction to opioids including prescription pain relievers, heroin, and synthetic opioids such as fentanyl caused a serious national crisis in the United States (US), that affects public health as well as social and economic welfare [1]. The first wave began in the 1990s with the rises of death cases related to overdose of prescription opioids. The third wave began in 2013 with the sharp rise of overdose death numbers involving synthetic opioids, illicitly manufactured fentanyl (IMF). In the US alone, more than 47,000 opioidrelated overdose deaths occurred during 2017, which are closely related to synthetic opioids, especially fentanyl [2]. IMF fatalities are generally due to co-administration of other illicit drugs, such as cocaine, heroin, and methamphetamine [6, 7], which leads to overdose and death. One of the potential pharmacotherapies may involve kratom's major indole alkaloid, mitragynine, since kratom (Mitragyna speciosa Korth.) preparations have been reported to alleviate opiate withdrawal signs in self-treatment in Malaysian opiate addicts
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