Gully Brian J, Brown Zoe E, Hornbacher Rivkah, Brown Joshua C, Back Sudie E, McCance-Katz Elinore F, Swift Robert M, Haass-Koffler Carolina L
Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island.
Neuroscience Graduate Program, Brown University, Providence, Rhode Island.
Biol Psychiatry Glob Open Sci. 2024 Sep 18;5(1):100395. doi: 10.1016/j.bpsgos.2024.100395. eCollection 2025 Jan.
Intranasal administration of the neuropeptide oxytocin has been explored as a potential therapeutic agent for substance use disorder including opioid use disorder (OUD).
This phase 1, crossover, randomized, double-blind, placebo-controlled trial tested the safety, tolerability, and efficacy of intranasal oxytocin (80 IU) twice a day for 7 days in participants ( = 20) with OUD who were taking an opioid agonist therapy. In the laboratory, participants underwent opioid cue exposure paired with noradrenergic activation produced by yohimbine (32.4 mg) or placebo. Assessments included, 1) subjective response: craving, withdrawal, anxiety, and stress; 2) biomedical markers: hypothalamic-pituitary-adrenal axis response (cortisol) and noradrenergic activation (α-amylase); and 3) safety measures: hemodynamics and adverse event evaluation. Generalized linear model with model-based estimator in the covariance matrix was used, with medication (oxytocin/placebo) and noradrenergic activation (yohimbine/placebo) as within-subject factors.
Oxytocin significantly reduced opioid-like withdrawal, anxiety symptoms, and cortisol levels elicited by cue exposure under noradrenergic activation produced by yohimbine. This effect was specific because oxytocin did not reduce craving, hemodynamics, or α-amylase levels increased by yohimbine administration. A single dose of yohimbine elicited the noradrenergic stimulation, and 7-day oxytocin administration was safe and well tolerated among individuals diagnosed with OUD and taking opioid agonist therapy.
The findings of this study suggest that oxytocin alleviates opioid-like withdrawal symptoms and anxiety by modulating the hypothalamic-pituitary-adrenal axis.
鼻内给予神经肽催产素已被探索作为包括阿片类物质使用障碍（OUD）在内的物质使用障碍的一种潜在治疗药物。
这项1期交叉、随机、双盲、安慰剂对照试验，测试了每天两次鼻内给予催产素（80国际单位），持续7天，对正在接受阿片类激动剂治疗的OUD参与者（n = 20）的安全性、耐受性和疗效。在实验室中，参与者接受与育亨宾（32.4毫克）或安慰剂产生的去甲肾上腺素能激活配对的阿片类线索暴露。评估包括：1）主观反应：渴望、戒断、焦虑和压力；2）生物医学标志物：下丘脑 - 垂体 - 肾上腺轴反应（皮质醇）和去甲肾上腺素能激活（α - 淀粉酶）；3）安全措施：血流动力学和不良事件评估。使用协方差矩阵中基于模型估计器的广义线性模型，将药物（催产素/安慰剂）和去甲肾上腺素能激活（育亨宾/安慰剂）作为受试者内因素。
在育亨宾产生的去甲肾上腺素能激活下，催产素显著降低了线索暴露引起的阿片样戒断、焦虑症状和皮质醇水平。这种作用是特异性的，因为催产素并未降低育亨宾给药引起的渴望、血流动力学或α - 淀粉酶水平。单剂量育亨宾引发了去甲肾上腺素能刺激，并且在诊断为OUD并接受阿片类激动剂治疗的个体中，7天的催产素给药是安全且耐受性良好的。
本研究结果表明，催产素通过调节下丘脑 - 垂体 - 肾上腺轴来减轻阿片样戒断症状和焦虑。
