OBJECTIVE Resting-state (rs) network dysfunction is a contributing factor to treatment resistance in epilepsy. In treatment-resistant epilepsy (TRE), pharmacological and nonpharmacological therapies have been shown to improve such dysfunction. In this study, our goal was to prospectively evaluate the effect of highly purified plant-derived cannabidiol (CBD; Epidiolex®) on rs functional magnetic resonance imaging (fMRI) functional connectivity (rs-FC). We hypothesized that CBD would change and potentially normalize the rs-FC in TRE. METHODS Twenty-two of 27 participants with TRE completed all study procedures including longitudinal pre-/on-CBD rs-fMRI (8M/14F, mean age = 36.2 ± 15.9 years, TRE duration = 18.3 ± 12.6 years); there were no differences in age (p = 0.99) or sex (p = 0.15) between groups. Assessments collected included seizure frequency (SF), Chalfont Seizure Severity Scale (CSSS), Columbia Suicide Severity Rating Scale (C-SSRS), Adverse Events Profile (AEP), and Profile of Mood States (POMS). Twenty-three healthy controls (HCs) received rs-fMRI and POMS once. RESULTS Participants with TRE showed average decrease of 71.7% in SF (p < 0.0001) and improved CSSS, AEP, and POMS confusion, depression, and fatigue subscores (all p < 0.05) on-CBD with POMS scores becoming similar to those of HCs. Paired t-tests showed significant pre-/on-CBD changes in rs-FC in cerebellum, frontal areas, temporal areas, hippocampus, and amygdala with some of them correlating with improvement in behavioral measures. Significant differences in rs-FC between pre-CBD and HCs were found in cerebellum, frontal, and occipital regions. After controlling for changes in SF with CBD, these differences were no longer present when comparing on-CBD to HCs. SIGNIFICANCE This study indicates that highly purified CBD modulates and potentially normalizes rs-FC in the epileptic brain. This effect may underlie its efficacy. This study provides Class III evidence for CBD's normalizing effect on rs-FC in TRE.

中文翻译：

---

大麻二酚使难治性癫痫的静息状态功能连接正常化

目的 静息状态 (rs) 网络功能障碍是导致癫痫治疗抵抗的一个因素。在难治性癫痫 (TRE) 中，药物和非药物疗法已被证明可以改善这种功能障碍。在这项研究中，我们的目标是前瞻性地评估高纯度植物来源的大麻二酚（CBD；Epidiolex®）对 rs 功能磁共振成像（fMRI）功能连接（rs-FC）的影响。我们假设 CBD 会改变并可能使 TRE 中的 rs-FC 正常化。方法 27 名 TRE 参与者中有 22 名完成了所有研究程序，包括纵向 CBD 前/上 rs-fMRI（8M/14F，平均年龄 = 36.2 ± 15.9 岁，TRE 持续时间 = 18.3 ± 12.6 岁）；组间的年龄（p = 0.99）或性别（p = 0.15）没有差异。收集的评估包括癫痫发作频率 (SF)、查尔方特癫痫严重程度量表 (CSSS)、哥伦比亚自杀严重程度评定量表 (C-SSRS)、不良事件概况 (AEP) 和情绪状态概况 (POMS)。二十三个健康对照 (HC) 接受一次 rs-fMRI 和 POMS。结果 TRE 参与者的 SF 平均下降 71.7% (p < 0.0001) 并改善 CSSS、AEP 和 POMS 的混乱、抑郁和疲劳分项 (均 p < 0.05) 在 CBD 上，POMS 分数变得与 HC 相似. 配对 t 检验显示小脑、额叶区、颞区、海马和杏仁核中 rs-FC 的 CBD 前/CBD 变化显着，其中一些与行为测量的改善相关。在小脑、额叶和枕叶区域发现前 CBD 和 HC 之间 rs-FC 的显着差异。在控制了 SF 与 CBD 的变化后，将 on-CBD 与 HC 进行比较时，这些差异不再存在。意义 这项研究表明，高度纯化的 CBD 可以调节癫痫脑中的 rs-FC，并可能使其正常化。这种效果可能是其功效的基础。该研究为 CBD 对 TRE 中 rs-FC 的正常化作用提供了 III 类证据。