Kratom for Self-Treatment of Opioid Addiction and Withdrawal

"Mitragyna speciosa, or kratom, a natural plant product native to Southeast Asia, has recently gained popularity in regards for its use in self-treatment of opioid addiction and withdrawal syndrome (Boyer et al. 2008; Kruegel and Grundmann 2018; Singh et al. 2020; Chakraborty and Majumdar 2020). Mitragynine, the main active alkaloid in kratom, has been found to make up approximately 66% of the extract content within the plant (Adkins et al. 2011; Hassan et al. 2013). An initial study reported that a single administration of mitragynine reduced behavioral signs of withdrawal in morphine-dependent rats (Hassan et al. 2020). Although a mechanism was not investigated, previous studies with mitragynine show that most of its physiological effects are via the MOR subtype (Yusoff et al. 2014; Matsumoto et al. 1996a; Kruegel et al. 2019). Similarly, the semi-synthetic analog mitragynine pseudoindoxyl (MP) demonstrated potent antinociception with reduced liabilities attributed to its multifunctional MOR biased agonism and DOR antagonism (Váradi et al. 2016). Recent in vitro studies also suggest that mitragynine pseudoindoxyl is a metabolite of mitragynine (Kamble et al. 2020). Lyophilized kratom tea itself has been shown to act via the opioid system (Yusoff et al. 2014; Wilson et al. 2020), mitigate opioid withdrawal syndrome in zebra fish (Khor et al. 2011), and substitute for morphine in rodent discrimination studies (Harun et al. 2015)."