Department of Psychiatry and Behavioral Sciences, UTHealth McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Department of Psychiatry and Behavioral Sciences, UTHealth McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Brain Res. 2020 Mar 15;1731:146359. doi: 10.1016/j.brainres.2019.146359. Epub 2019 Jul 30.
Current evidence and literature reviews provide a strong justification for examining the orexin receptor (OXR) system as a therapeutic target in substance use disorders, including cocaine and other psychostimulants.
In this preliminary, proof-of-concept examination of orexin modulation in humans with cocaine use disorder, we measured changes in domains tied to relapse: stress, sleep, cue reactivity, and inhibitory control. Additionally, mood symptoms (anxiety, depression), medication compliance, and side effects were assessed.
Twenty non-treatment seeking subjects with cocaine use disorder (CUD) received either the OXR / OXR antagonist suvorexant PO or placebo at 10 PM daily for two weeks (10 mg week 1, 20 mg week 2). Using psychometrics, smart-watch actigraphy, a cold-pressor stress challenge, and eye-tracking technology, the following domains were examined: sleep, stress/anxiety, cue-reactivity (attentional bias, craving), and inhibitory control. Psychometric data were collected every M/W/F (7 time points). Laboratory data were collected weekly (3 time points).
Bayesian and frequentist generalized linear models were employed in parallel to examine the effects of suvorexant compared to placebo, with a Bayesian posterior probability threshold >80% as evidence of a signal for suvorexant. Notable results favoring suvorexant over placebo included fewer total anti-saccade errors, improved sleep actigraphy (sleep/awake periods), pre/post cold-pressor change in heart rate and salivary cortisol (all posterior probabilities >94%), and craving (posterior probability >87%).
Initial but restricted evidence is provided supporting the orexin system as a modulator of relapse-related processes in cocaine use disorder. Baseline differences in the main outcome variables were not experimentally controlled and differences in craving were observed at baseline. This, in combination with a limited sample size, constrain the nature of the project. The results may serve to inform more comprehensive future research.
现有证据和文献综述为研究食欲素受体（OXR）系统作为物质使用障碍的治疗靶点提供了强有力的依据，包括可卡因和其他精神兴奋剂。
在这项初步的、探索性的可卡因使用障碍患者中食欲素调节的研究中，我们测量了与复发相关的领域的变化：压力、睡眠、线索反应和抑制控制。此外，还评估了情绪症状（焦虑、抑郁）、药物依从性和副作用。
20 名非治疗性寻求可卡因使用障碍（CUD）的受试者每天晚上 10 点口服 OXR/OXR 拮抗剂苏沃雷生（PO）或安慰剂，为期两周（第 1 周 10mg，第 2 周 20mg）。使用心理测量学、智能手表活动记录仪、冷压应激挑战和眼动追踪技术，检查以下领域：睡眠、压力/焦虑、线索反应（注意力偏差、渴望）和抑制控制。心理测量数据每 M/W/F 收集（7 个时间点）。实验室数据每周收集（3 个时间点）。
贝叶斯和频率主义广义线性模型并行用于检查苏沃雷生与安慰剂相比的效果，贝叶斯后验概率阈值>80%作为苏沃雷生信号的证据。苏沃雷生优于安慰剂的显著结果包括总反扫视错误减少、睡眠活动记录仪改善（睡眠/觉醒期）、冷压前后心率和唾液皮质醇变化（后验概率均>94%）和渴望（后验概率>87%）。
提供了初步但有限的证据，支持食欲素系统作为可卡因使用障碍复发相关过程的调节剂。主要结局变量的基线差异未进行实验控制，并且在基线时观察到渴望的差异。这一点，加上样本量有限，限制了项目的性质。结果可能有助于为更全面的未来研究提供信息。
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