Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, United States of America.
Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, United States of America.
Epilepsy Behav. 2020 Sep;110:107152. doi: 10.1016/j.yebeh.2020.107152. Epub 2020 Jun 22.
Current antiepileptic drugs (AEDs) are undesirable for many reasons including the inability to reduce seizures in certain types of epilepsy, such as Dravet syndrome (DS) where in one-third of patients does not respond to current AEDs, and severe adverse effects that are frequently experienced by patients. Epidiolex, a cannabidiol (CBD)-based drug, was recently approved for treatment of DS. While Epidiolex shows great promise in reducing seizures in patients with DS, it is used in conjunction with other AEDs and can cause liver toxicity. To investigate whether other cannabis-derived compounds could also reduce seizures, the antiepileptic effects of CBD, Δ9-tetrahydrocannabinol (THC), cannabidivarin (CBDV), cannabinol (CBN), and linalool (LN) were compared in both a chemically-induced (pentylenetetrazole, PTZ) and a DS (scn1Lab) seizure models. Zebrafish (Danio rerio) that were either wild-type (Tupfel longfin) or scn1Lab (DS) were exposed to CBD, THC, CBDV, CBN, or LN for 24 h from 5 to 6 days postfertilization. Following exposure, total distance traveled was measured in a ViewPoint Zebrabox to determine if these compounds reduced seizure-like activity. Cannabidiol (0.6 and 1 μM) and THC (1 and 4 μM) significantly reduced PTZ-induced total distance moved. At the highest THC concentration, the significant reduction in PTZ-induced behavior was likely the result of sedation as opposed to antiseizure activity. In the DS model, CBD (0.6 μM), THC (1 μM), CBN (0.6 and 1 μM), and LN (4 μM) significantly reduced total distance traveled. Cannabinol was the most effective at reducing total distance relative to controls. In addition to CBD, other cannabis-derived compounds showed promise in reducing seizure-like activity in zebrafish. Specifically, four of the five compounds were effective in the DS model, whereas in the PTZ model, only CBD and THC were, suggesting a divergence in the mode of action among the cannabis constituents.
目前的抗癫痫药物（AEDs）由于多种原因不理想，包括无法减少某些类型的癫痫发作，例如 Dravet 综合征（DS），其中三分之一的患者对目前的 AEDs 没有反应，以及患者经常经历的严重不良反应。Epidiolex，一种基于大麻二酚（CBD）的药物，最近被批准用于治疗 DS。虽然 Epidiolex 在减少 DS 患者的癫痫发作方面显示出巨大的潜力，但它与其他 AED 联合使用，可能会导致肝毒性。为了研究其他大麻衍生化合物是否也能减少癫痫发作，比较了 CBD、Δ9-四氢大麻酚（THC）、大麻二酚（CBDV）、大麻酚（CBN）和芳樟醇（LN）在化学诱导（戊四氮，PTZ）和 DS（scn1Lab）癫痫模型中的抗癫痫作用。从受精后 5 到 6 天，将野生型（Tupfel longfin）或 scn1Lab（DS）斑马鱼暴露于 CBD、THC、CBDV、CBN 或 LN 中 24 小时。暴露后，在 ViewPoint Zebrabox 中测量总行进距离，以确定这些化合物是否减少癫痫样活动。CBD（0.6 和 1 μM）和 THC（1 和 4 μM）显著减少了 PTZ 诱导的总行进距离。在最高 THC 浓度下，PTZ 诱导行为的显著减少可能是镇静作用而不是抗癫痫作用的结果。在 DS 模型中，CBD（0.6 μM）、THC（1 μM）、CBN（0.6 和 1 μM）和 LN（4 μM）显著减少了总行进距离。与对照相比，大麻醇在减少总距离方面最有效。除了 CBD，其他大麻衍生化合物在减少斑马鱼的癫痫样活动方面显示出前景。具体来说，在 DS 模型中，五种化合物中有四种有效，而在 PTZ 模型中，只有 CBD 和 THC 有效，这表明大麻成分的作用模式存在差异。
