McKendrick Greer, Clapham Charlotte, Zipunnikov Vadim, Ellis Jennifer D, Finan Patrick, Dunn Kelly E, Strain Eric C, Wolinsky David, Huhn Andrew S
Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States.
Psychoneuroendocrinology. 2025 Aug 6;180:107570. doi: 10.1016/j.psyneuen.2025.107570.
Decades of research efforts have described the negative impact that stress poses on successful treatment of Opioid Use Disorder (OUD). However, direct investigation of biological and self-reported stress, and the relationship between the two during opioid withdrawal is understudied. This study investigated whether a dual orexin-receptor antagonist alters the relationship between stress and opioid withdrawal among persons undergoing a buprenorphine taper. Persons diagnosed with OUD (N = 38) were enrolled in a residential, randomized controlled trial wherein they were stabilized on buprenorphine/naloxone before being randomized to receive 20 mg suvorexant, 40 mg suvorexant, or placebo. Participants then underwent a 4-day step-wise buprenorphine taper followed by a 4-day post-taper observation period. Patient-reported levels of stress, withdrawal, and craving, as well as salivary cortisol samples, were collected four times daily. The results demonstrated that total daily cortisol levels decreased during the buprenorphine taper across medication groups and were significantly lower in those administered suvorexant vs placebo. Those receiving suvorexant also rated their stress as significantly lower relative to placebo. A lagged statistical model assessing the relationship between daily reports of stress and diurnal cortisol slope found a reciprocal relationship between a flatter previous day cortisol slope with higher next day self-reported stress. Greater total daily cortisol was associated with greater opioid withdrawal severity, and greater patient-reported stress was associated with greater opioid withdrawal and craving throughout the study. These findings advance our understanding of the relationship among the orexin neurotransmitter system and stress during opioid withdrawal.
数十年的研究工作已经描述了压力对阿片类物质使用障碍（OUD）成功治疗所造成的负面影响。然而，对于生物应激和自我报告的应激，以及在阿片类物质戒断期间两者之间的关系，尚未进行充分研究。本研究调查了双重食欲素受体拮抗剂是否会改变接受丁丙诺啡减量治疗的人群中应激与阿片类物质戒断之间的关系。诊断为OUD的患者（N = 38）参加了一项住院随机对照试验，在该试验中，他们先在丁丙诺啡/纳洛酮上实现稳定，然后被随机分配接受20毫克苏沃雷生、40毫克苏沃雷生或安慰剂。参与者随后进行了为期4天的逐步丁丙诺啡减量，接着是4天的减量后观察期。每天收集四次患者报告的应激、戒断和渴望水平，以及唾液皮质醇样本。结果表明，在整个药物组中，丁丙诺啡减量期间每日皮质醇总水平下降，服用苏沃雷生的患者的皮质醇总水平显著低于服用安慰剂的患者。与安慰剂相比，服用苏沃雷生的患者也将他们的应激程度评定为显著更低。一个评估每日应激报告与昼夜皮质醇斜率之间关系的滞后统计模型发现，前一天皮质醇斜率较平缓与第二天自我报告的应激程度较高之间存在相互关系。在整个研究中，每日皮质醇总量越高与阿片类物质戒断严重程度越高相关，患者报告的应激程度越高与阿片类物质戒断及渴望程度越高相关。这些发现推进了我们对食欲素神经递质系统与阿片类物质戒断期间应激之间关系的理解。
