Cannabidiol, approved for treatment of pediatric refractory epilepsy, has anti-seizure effects in various animal seizure models. Chemical warfare nerve agents, including soman, are organophosphorus chemicals that can induce seizure and death if untreated or if treatment is delayed. Our objective was to evaluate whether cannabidiol would ameliorate soman-induced toxicity using a mouse model that similar to humans lacks plasma carboxylesterase. In the present study, adult female plasma carboxylesterase knockout (Es1-/-) mice were pre-treated with cannabidiol (20−150 mg/kg) or vehicle 1 h prior to exposure to a seizure-inducing dose of soman and evaluated for survival and seizure activity. The muscarinic antagonist atropine sulfate and the oxime HI-6 were administered at 1 min after exposure, and the benzodiazepine midazolam was administered at 30 min after seizure onset. Cannabidiol (150 mg/kg) pre-treatment led to a robust increase in survival rate and attenuated body weight loss in soman-exposed mice treated with medical countermeasures, compared to mice pre-treated with vehicle. In addition, mice pretreated with cannabidiol (150 mg/kg) had a modest reduction in seizure severity after midazolam treatment compared to vehicle-pretreated. These findings of improved outcome with cannabidiol administration in a severe seizure model of soman exposure provide additional pre-clinical support for the benefits of cannabidiol against exposure to seizure-inducing chemical agents and suggest cannabidiol may augment the anti-seizure effects of midazolam.

大麻二酚被批准用于治疗小儿难治性癫痫，在各种动物癫痫模型中具有抗癫痫作用。化学战神经毒剂，包括梭曼，是有机磷化学物质，如果不及时治疗或延迟治疗，会导致癫痫发作和死亡。我们的目标是使用类似于人类缺乏血浆羧酸酯酶的小鼠模型来评估大麻二酚是否会改善梭曼诱导的毒性。在本研究中，成年雌性血浆羧酸酯酶敲除 (Es1-/-) 小鼠在暴露于诱发癫痫发作剂量的 soman 前 1 小时用大麻二酚 (20-150 mg/kg) 或载体进行预处理，并评估其存活率和扣押活动。毒蕈碱拮抗剂硫酸阿托品和肟 HI-6 在暴露后 1 分钟给药，并且在癫痫发作后 30 分钟给予苯二氮卓咪达唑仑。与用媒介物预处理的小鼠相比，大麻二酚 (150 毫克/千克) 预处理导致接受药物治疗的索曼暴露小鼠的存活率显着增加并减轻体重减轻。此外，与媒介物预处理相比，用大麻二酚 (150 mg/kg) 预处理的小鼠在咪达唑仑治疗后癫痫发作严重程度适度降低。在 soman 暴露的严重癫痫发作模型中使用大麻二酚改善结果的这些发现为大麻二酚对暴露于诱发癫痫发作的化学制剂的益处提供了额外的临床前支持，并表明大麻二酚可能会增强咪达唑仑的抗癫痫作用。与用媒介物预处理的小鼠相比，大麻二酚 (150 毫克/千克) 预处理导致接受药物治疗的索曼暴露小鼠的存活率显着增加并减轻体重减轻。此外，与媒介物预处理相比，用大麻二酚 (150 mg/kg) 预处理的小鼠在咪达唑仑治疗后癫痫发作严重程度适度降低。在 soman 暴露的严重癫痫发作模型中使用大麻二酚改善结果的这些发现为大麻二酚对暴露于诱发癫痫发作的化学制剂的益处提供了额外的临床前支持，并表明大麻二酚可能会增强咪达唑仑的抗癫痫作用。与用媒介物预处理的小鼠相比，大麻二酚 (150 毫克/千克) 预处理导致接受药物治疗的索曼暴露小鼠的存活率显着增加并减轻体重减轻。此外，与媒介物预处理相比，用大麻二酚 (150 mg/kg) 预处理的小鼠在咪达唑仑治疗后癫痫发作严重程度适度降低。在 soman 暴露的严重癫痫发作模型中使用大麻二酚改善结果的这些发现为大麻二酚对暴露于诱发癫痫发作的化学制剂的益处提供了额外的临床前支持，并表明大麻二酚可能会增强咪达唑仑的抗癫痫作用。与媒介物预处理相比，用大麻二酚 (150 mg/kg) 预处理的小鼠在咪达唑仑治疗后癫痫发作的严重程度略有降低。在 soman 暴露的严重癫痫发作模型中使用大麻二酚改善结果的这些发现为大麻二酚对暴露于诱发癫痫发作的化学制剂的益处提供了额外的临床前支持，并表明大麻二酚可能会增强咪达唑仑的抗癫痫作用。与媒介物预处理相比，用大麻二酚 (150 mg/kg) 预处理的小鼠在咪达唑仑治疗后癫痫发作的严重程度略有降低。在 soman 暴露的严重癫痫发作模型中使用大麻二酚改善结果的这些发现为大麻二酚对暴露于诱发癫痫发作的化学制剂的益处提供了额外的临床前支持，并表明大麻二酚可能会增强咪达唑仑的抗癫痫作用。