Vilela Luciano R, Lima Isabel V, Kunsch Érica B, Pinto Hyorrana Priscila P, de Miranda Aline S, Vieira Érica Leandro M, de Oliveira Antônio Carlos P, Moraes Marcio Flávio D, Teixeira Antônio L, Moreira Fabricio A
Graduate School in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Brazil.
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Brazil.
Epilepsy Behav. 2017 Oct;75:29-35. doi: 10.1016/j.yebeh.2017.07.014. Epub 2017 Aug 16.
Cannabidiol (CBD), the main nonpsychotomimetic compound from Cannabis sativa, inhibits experimental seizures in animal models and alleviates certain types of intractable epilepsies in patients. Its pharmacological profile, however, is still uncertain. Here we tested the hypothesis that CBD anticonvulsant mechanisms are prevented by cannabinoid (CB and CB) and vanilloid (TRPV1) receptor blockers. We also investigated its effects on electroencephalographic (EEG) activity and hippocampal cytokines in the pentylenetetrazole (PTZ) model. Pretreatment with CBD (60mg/kg) attenuated seizures induced by intraperitoneal, subcutaneous, and intravenous PTZ administration in mice. The effects were reversed by CB, CB, and TRPV1 selective antagonists (AM251, AM630, and SB366791, respectively). Additionally, CBD delayed seizure sensitization resulting from repeated PTZ administration (kindling). This cannabinoid also prevented PTZ-induced EEG activity and interleukin-6 increase in prefrontal cortex. In conclusion, the robust anticonvulsant effects of CBD may result from multiple pharmacological mechanisms, including facilitation of endocannabinoid signaling and TRPV1 mechanisms. These findings advance our understanding on CBD inhibition of seizures, EEG activity, and cytokine actions, with potential implications for the development of new treatments for certain epileptic syndromes.
大麻二酚（CBD）是大麻中的主要非致幻化合物，可抑制动物模型中的实验性癫痫发作，并缓解患者某些类型的顽固性癫痫。然而，其药理特性仍不明确。在此，我们检验了大麻素（CB1和CB2）及香草酸受体（TRPV1）阻滞剂可阻止CBD抗惊厥机制的假说。我们还在戊四氮（PTZ）模型中研究了其对脑电图（EEG）活动及海马细胞因子的影响。用CBD（60mg/kg）预处理可减轻小鼠腹腔内、皮下及静脉注射PTZ所诱发的癫痫发作。这些作用分别被CB1、CB2及TRPV1选择性拮抗剂（分别为AM251、AM630和SB366791）逆转。此外，CBD可延缓因重复给予PTZ（点燃）所致的癫痫发作致敏。这种大麻素还可阻止PTZ诱导的前额叶皮质EEG活动及白细胞介素-6升高。总之，CBD强大的抗惊厥作用可能源于多种药理机制，包括促进内源性大麻素信号传导及TRPV1机制。这些发现增进了我们对CBD抑制癫痫发作、EEG活动及细胞因子作用的理解，对开发某些癫痫综合征的新疗法具有潜在意义。
