There is significant interest in the use of cannabinoids for the treatment of many epilepsies including absence epilepsy (AE). Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model many aspects of AE including the presence of spike-and-wave discharges (SWDs) on electroencephalogram (EEG) and behavioral comorbidities, such as elevated anxiety. However, the effects of cannabis plant-based phytocannabinoids have not been tested in GAERS. Therefore, we investigated how SWDs in GAERS are altered by the two most common phytocannabinoids, Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD), and exposure to smoke from two different chemovars of cannabis. Animals were implanted with bipolar electrodes in the somatosensory cortex and EEGs were recorded for 2 hr. Injected THC (1–10 mg/kg, i.p.) dose-dependently increased SWDs to over 200% of baseline. In contrast, CBD (30–100 mg/kg, i.p.) produced a ~50% reduction in SWDs. Exposure to smoke from a commercially available chemovar of high-THC cannabis (Mohawk, Aphria Inc.) increased SWDs whereas a low-THC/high-CBD chemovar of cannabis (Treasure Island, Aphria Inc.) did not significantly affect SWDs in GAERS. Pre-treatment with a CB1R antagonist (SR141716A) did not prevent the high-THC cannabis smoke from increasing SWDs, suggesting that the THC-mediated increase may not be CB1R-dependent. Plasma concentrations of THC and CBD were similar to previously reported values following injection and smoke exposure. Compared to injected CBD, it appears Treasure Island did not increase plasma levels sufficiently to observe an anti-epileptic effect. Together these experiments provide initial evidence that acute phytocannabinoid administration exerts the biphasic modulation of SWDs and may differentially impact patients with AE.

中文翻译：

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斯特拉斯堡遗传缺失癫痫大鼠暴露于注射大麻素和吸食大麻后尖峰和波放电的可分离变化

人们对使用大麻素治疗包括失神性癫痫 (AE) 在内的许多癫痫非常感兴趣。来自斯特拉斯堡的遗传缺失癫痫大鼠 (GAERS) 模拟了 AE 的许多方面，包括脑电图 (EEG) 和行为合并症（例如焦虑升高）上存在棘波放电 (SWD)。然而，基于大麻植物的植物大麻素的影响尚未在 GAERS 中进行测试。因此，我们研究了 GAERS 中的 SWD 如何被两种最常见的植物大麻素 Δ ^9改变。- 四氢大麻酚 (THC) 和大麻二酚 (CBD)，以及接触两种不同大麻化学变种的烟雾。动物在体感皮层植入双极电极，记录脑电图 2 小时。注射的 THC（1-10 mg/kg，ip）剂量依赖性地将 SWD 增加到基线的 200% 以上。相比之下，CBD (30–100 mg/kg, ip) 使 SWDs 减少了约 50%。暴露于高 THC 大麻（Mohawk，Aphria Inc.）的市售化学变剂的烟雾中会增加 SWD，而大麻的低 THC/高 CBD 化学变剂（Treasure Island，Aphria Inc.）并未显着影响 GAERS 中的 SWD。用 CB1R 拮抗剂 (SR141716A) 进行预处理并不能阻止高 THC 大麻烟雾增加 SWD，这表明 THC 介导的增加可能不依赖于 CB1R。THC 和 CBD 的血浆浓度与之前报道的注射和烟雾暴露后的值相似。与注射的 CBD 相比，金银岛似乎没有将血浆水平提高到足以观察到抗癫痫作用。这些实验共同提供了初步证据，表明急性植物大麻素给药对 SWD 施加双相调节，并可能对 AE 患者产生不同的影响。