Data sharing for research article entitled "Kratom Use Disorder and Unfolded Protein Response: Evaluating Their Relationship in a Case Control Study" published in Plos One.

Kratom (Mitragyna speciosa Korth), traditionally used as remedies for various illnesses in Southeast Asia, is currently widely used globally to improve mood and anxiety, enhance endurance, and as a self-prescribed replacement for opioid dependence and as an analgesic for chronic pain. Despite its therapeutic potential, its capacity to induce withdrawal symptoms on abstinence and risk of kratom dependence due to its opioid-like effects has been a major drawback to its potential as a therapeutic agent. Endoplasmic reticulum (ER) stress occurred when there is a perturbation of protein folding in the ER lumen which leads to the accumulation of misfolded and unfolded protein in ER. Unfolded protein response (UPR) occurred upon ER stress which aims to counteract ER stress by reducing unfolded or misfolded protein to maintain ER homeostasis. However, if UPR is incapable of counteracting ER stress, the persistent occurrence of ER stress will ultimately lead to cell apoptosis. Psychostimulant use (methamphetamine and cocaine) has been linked to occurrence of ER stress. Despite kratom does exhibit psychostimulant properties, data on how regular kratom consumption and ER stress are link to kratom use disorder is lacking. Hence, this study filled the research gap by: [1] comparing ER stress sensor protein expression (BiP, XBP1, ATF4, CHOP, JNK, and p-JNK) between regular kratom users and healthy non-drug using controls, [2] determining the association between kratom use characteristics, targeted ER stress sensor protein expression, and “kratom use disorder” diagnosed with Diagnostic and Statistical Manual for Mental Disorders 5th Edition (DSM-5) among regular kratom users. In this study, we recruited 60 regular kratom users and 50 healthy control subjects and they were administered: demographic and clinical characteristics questionnaire (all participants), the kratom use characteristics questionnaire and DSM-5 diagnostic criteria for substance use disorder related to kratom use (only kratom users). Blood samples were collected from all participants and targeted ER stress sensor protein expression was analyzed with Western blotting. Our findings revealed that the relative protein expression of all the targeted ER stress sensors was higher among kratom users compared with healthy controls. In addition, the relative protein expression of CHOP, JNK, and p-JNK was higher compared to that of BiP, XBP1, and ATF4 among the kratom users. Higher protein expression of CHOP and p-JNK increased the odds of kratom use disorder occurrence. Kratom use characteristics and other ER stress sensor protein expression were not associated with kratom use disorder. Hence, we conclude regular kratom use may induce protracted ER stress leading to the decompensation of UPR to maintain ER homeostasis. This may link to higher odds of kratom use disorder.