Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Lublin, Poland.
Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
Neuropharmacology. 2019 Nov 1;158:107733. doi: 10.1016/j.neuropharm.2019.107733. Epub 2019 Aug 1.
Cannabidiol and cannabidiol-enriched products have recently attracted much attention as an add-on therapy for epilepsy, especially drug-resistant seizures. It should be, however, remembered that concomitant use of cannabidiol and antiepileptic drugs may pose a risk of interactions between them. For this reason, the aim of our study was to assess the effect of cannabidiol on the activity of selected new antiepileptic drugs in the electrically-induced seizure models in mice. We studied the effect of cannabidiol on the anticonvulsant action of topiramate, oxcarbazepine, lamotrigine, and pregabalin in the maximal electroshock-induced seizure test as well as on the activity of levetiracetam, tiagabine, lacosamide, and gabapentin in the 6 Hz seizure test in mice. We showed that cannabidiol increased the activity of topiramate, oxcarbazepine, pregabalin, tiagabine, and gabapentin. It did not affect the anticonvulsant effect of lamotrigine and lacosamide. Interestingly, cannabidiol attenuated the anticonvulsant activity of levetiracetam. Co-administration of antiepileptic drugs with cannabidiol did not cause adverse effects such as impairment of motor coordination, changes in neuromuscular strength or potentiation of the cannabidiol-induced hypolocomotion. Serum and brain levels of antiepileptic drugs and cannabidiol were determined by using HPLC in order to ascertain any pharmacokinetic contribution to the observed behavioral effects. Only interaction with levetiracetam was purely pharmacodynamic in nature because no changes in serum and brain concentration of either levetiracetam or cannabidiol were observed. Increased anticonvulsant activity of topiramate, oxcarbazepine, pregabalin, tiagabine, and gabapentin could be, at least in part, related to pharmacokinetic interactions with cannabidiol because there were changes in serum and/or brain concentrations of antiepileptic drugs and/or cannabidiol. Pharmacokinetic interactions cannot be also excluded between lacosamide and cannabidiol because cannabidiol increased brain concentration of lacosamide and lacosamide increased brain concentration of cannabidiol. Further pharmacokinetic studies are required to evaluate the type of interactions between cannabidiol and novel antiepileptic drugs.
大麻二酚及其富含大麻二酚的产品最近作为癫痫的附加治疗方法引起了广泛关注，尤其是对耐药性癫痫发作。然而，应该记住，大麻二酚与抗癫痫药物同时使用可能会导致它们之间存在相互作用的风险。出于这个原因，我们的研究目的是评估大麻二酚对几种新型抗癫痫药物在电诱导癫痫模型中活性的影响。我们研究了大麻二酚对托吡酯、奥卡西平、拉莫三嗪和普瑞巴林在最大电休克诱导的癫痫发作模型中的抗惊厥作用的影响，以及大麻二酚对左乙拉西坦、噻加宾、拉科酰胺和加巴喷丁在 6Hz 癫痫发作模型中的活性的影响。我们表明，大麻二酚增加了托吡酯、奥卡西平、普瑞巴林、噻加宾和加巴喷丁的活性。它不影响拉莫三嗪和拉科酰胺的抗惊厥作用。有趣的是，大麻二酚减弱了左乙拉西坦的抗惊厥活性。与抗癫痫药物共同给予大麻二酚不会引起运动协调障碍、神经肌肉力量变化或增强大麻二酚诱导的运动功能减退等不良反应。使用 HPLC 测定抗癫痫药物和大麻二酚的血清和脑水平，以确定对观察到的行为效应的任何药代动力学贡献。只有与左乙拉西坦的相互作用具有纯粹的药效学性质，因为没有观察到左乙拉西坦或大麻二酚的血清和脑浓度的变化。托吡酯、奥卡西平、普瑞巴林、噻加宾和加巴喷丁的抗惊厥活性增加至少部分与大麻二酚的药代动力学相互作用有关，因为抗癫痫药物和/或大麻二酚的血清和/或脑浓度发生了变化。不能排除拉科酰胺和大麻二酚之间存在药代动力学相互作用，因为大麻二酚增加了拉科酰胺的脑浓度，而拉科酰胺增加了大麻二酚的脑浓度。需要进一步进行药代动力学研究来评估大麻二酚与新型抗癫痫药物之间的相互作用类型。
