Indriani Dwi Wahyu, Rahmawati Siti Irma, Bayu Asep, Ahmadi Peni, Sari Anissa Nofita, Zuraida Zuraida, Dharmayanti Ni Luh Putu Indi, Putra Masteria Yunovilsa
Research Center for Vaccine and Drugs, Research Organization for Health, National Research and Innovation Agency (BRIN), Jalan Raya Jakarta-Bogor Km. 46, Bogor, West Java, 16911, Indonesia.
Research Organization for Health, National Research and Innovation Agency (BRIN), Jalan Raya Jakarta-Bogor Km. 46, Bogor, West Java, 16911, Indonesia.
BMC Complement Med Ther. 2025 Jun 7;25(1):205. doi: 10.1186/s12906-025-04947-2.
Kratom alleviates pain by activating μu-opioid receptors (MOR), which trigger serotonin release to produce analgesia. Serotonin also interferes drug abuse effect. This study aimed to determine the role of serotonin in kratom-induced pain relief and withdrawal symptoms in mice.
The analgesic effect was assessed using the hot-plate test. To induce withdrawal symptoms, mice received naloxone after being treated with kratom extracts for five days at increasing doses. Another group of morphine-dependent mice was treated with kratom extracts to ameliorate their withdrawal symptoms. A molecular docking study and molecular dynamics were conducted to predict the binding target of alkaloid kratom for increasing serotonin levels.
Chronic administration of kratom alkaloid extract (20 mg/kg) produced analgesic effects comparable to morphine (10 mg/kg). In contrast, kratom crude extracts (10 mg/kg and 20 mg/kg) demonstrated lower analgesia activity. This analgesic effect was mediated by MOR activation, leading to decreased intracellular cAMP and increased serotonin transmission. Repeated and increasing doses of crude or alkaloid kratom extracts (8 mg/kg to 45 mg/kg) produced less severe withdrawal symptoms than morphine. Increased dopamine and serotonin levels contributed to the onset of withdrawal symptoms. In the morphine group, treatment with kratom extracts increased serotonin levels while reducing dopamine. Molecular docking and molecular dynamics result revealed that kratom alkaloids interacts more readily with tryptophan hydroxylase, the enzyme responsible for serotonin biosynthesis.
Kratom extracts have the potential to provide analgesic effects and withdrawal symptoms, both of which are mediated by elevated serotonin release.
kratom 通过激活 μu-阿片受体（MOR）来减轻疼痛，该受体触发血清素释放以产生镇痛作用。血清素也会干扰药物滥用效应。本研究旨在确定血清素在 kratom 诱导的小鼠疼痛缓解和戒断症状中的作用。
使用热板试验评估镇痛效果。为了诱导戒断症状，小鼠在以递增剂量用 kratom 提取物治疗五天后接受纳洛酮。另一组吗啡依赖小鼠用 kratom 提取物治疗以改善其戒断症状。进行了分子对接研究和分子动力学，以预测生物碱 kratom 增加血清素水平的结合靶点。
长期给予 kratom 生物碱提取物（20mg/kg）产生的镇痛效果与吗啡（10mg/kg）相当。相比之下，kratom 粗提取物（10mg/kg 和 20mg/kg）的镇痛活性较低。这种镇痛作用是由 MOR 激活介导的，导致细胞内 cAMP 减少和血清素传递增加。重复给予递增剂量的粗或生物碱 kratom 提取物（8mg/kg 至 45mg/kg）产生的戒断症状比吗啡轻。多巴胺和血清素水平升高导致戒断症状的出现。在吗啡组中，用 kratom 提取物治疗可增加血清素水平，同时降低多巴胺水平。分子对接和分子动力学结果表明，kratom 生物碱与色氨酸羟化酶（负责血清素生物合成的酶）更容易相互作用。
kratom 提取物有提供镇痛作用和戒断症状的潜力，两者均由血清素释放增加介导。
