Wilson Lisa L, Harris Hannah M, Eans Shainnel O, Brice-Tutt Ariana C, Cirino Thomas J, Stacy Heather M, Simons Chloe A, León Francisco, Sharma Abhisheak, Boyer Edward W, Avery Bonnie A, McLaughlin Jay P, McCurdy Christopher R
Department of Pharmacodynamics, University of Florida, Gainesville, FL, United States.
Department of Medicinal Chemistry, University of Florida, Gainesville, FL, United States.
Drug Alcohol Depend. 2020 Nov 1;216:108310. doi: 10.1016/j.drugalcdep.2020.108310. Epub 2020 Sep 22.
Made as a tea, the Thai traditional drug "kratom" reportedly possesses pharmacological actions that include both a coca-like stimulant effect and opium-like depressant effect. Kratom has been used as a substitute for opium in physically-dependent subjects. The objective of this study was to evaluate the antinociception, somatic and physical dependence produced by kratom tea, and then assess if the tea ameliorated withdrawal in opioid physically-dependent subjects.
Lyophilized kratom tea (LKT) was evaluated in C57BL/6J and opioid receptor knockout mice after oral administration. Antinociceptive activity was measured in the 55 °C warm-water tail-withdrawal assay. Potential locomotor impairment, respiratory depression and locomotor hyperlocomotion, and place preference induced by oral LKT were assessed in the rotarod, Comprehensive Lab Animal Monitoring System, and conditioned place preference assays, respectively. Naloxone-precipitated withdrawal was used to determine potential physical dependence in mice repeatedly treated with saline or escalating doses of morphine or LKT, and LKT amelioration of morphine withdrawal. Data were analyzed using one- and two-way ANOVA.
Oral administration of LKT resulted in dose-dependent antinociception (≥1 g/kg, p.o.) absent in mice lacking the mu-opioid receptor (MOR) and reduced in mice lacking the kappa-opioid receptor. These doses of LKT did not alter coordinated locomotion or induce conditioned place preference, and only briefly reduced respiration. Repeated administration of LKT did not produce physical dependence, but significantly decreased naloxone-precipitated withdrawal in morphine dependent mice.
The present study confirms the MOR agonist activity and therapeutic effect of LKT for the treatment of pain and opioid physical dependence.
据报道，泰国传统药物“ kratom”制成茶后具有药理作用，包括类似古柯的兴奋作用和类似鸦片的抑制作用。Kratom已被用作身体依赖者的鸦片替代品。本研究的目的是评估kratom茶产生的抗伤害感受、躯体和身体依赖性，然后评估该茶是否能改善阿片类药物身体依赖者的戒断症状。
口服给药后，在C57BL / 6J和阿片受体敲除小鼠中评估冻干的kratom茶（LKT）。在55°C温水甩尾试验中测量抗伤害感受活性。分别在转棒试验、综合实验动物监测系统和条件性位置偏爱试验中评估口服LKT引起的潜在运动功能损害、呼吸抑制和运动亢进以及位置偏爱。用纳洛酮诱发的戒断反应来确定反复用生理盐水或递增剂量的吗啡或LKT处理的小鼠的潜在身体依赖性，以及LKT对吗啡戒断的改善作用。使用单因素和双因素方差分析对数据进行分析。
口服LKT导致剂量依赖性抗伤害感受（≥1 g / kg，口服），在缺乏μ-阿片受体（MOR）的小鼠中不存在，而在缺乏κ-阿片受体的小鼠中降低。这些剂量的LKT不会改变协调运动或诱导条件性位置偏爱，只会短暂降低呼吸。反复给予LKT不会产生身体依赖性，但会显著降低吗啡依赖小鼠中纳洛酮诱发的戒断反应。
本研究证实了LKT的MOR激动剂活性以及对疼痛和阿片类药物身体依赖性的治疗作用。
