PDF(Pubmed)
Abstract：
Cannabinoids have shown potential in drug-resistant epilepsy treatment; however, we lack knowledge on which cannabinoid(s) to use, dosing, and their pharmacological targets. This study investigated (i) the anticonvulsant effect of Cannabidiol (CBD) alone and (ii) in combination with Delta-9 Tetrahydrocannabinol (Δ9-THC), as well as (iii) the serotonin (5-HT)1A receptor\'s role in CBD\'s mechanism of action. Seizure activity, induced by 4-aminopyridine, was measured by extracellular field recordings in cortex layer 2/3 of mouse brain slices. The anticonvulsant effect of 10, 30, and 100 µM CBD alone and combined with Δ9-THC was evaluated. To examine CBD\'s mechanism of action, slices were pre-treated with a 5-HT1A receptor antagonist before CBD\'s effect was evaluated. An amount of ≥30 µM CBD alone exerted significant anticonvulsant effects while 10 µM CBD did not. However, 10 µM CBD combined with low-dose Δ9-THC (20:3 ratio) displayed significantly greater anticonvulsant effects than either phytocannabinoid alone. Furthermore, blocking 5-HT1A receptors before CBD application significantly abolished CBD\'s effects. Thus, our results demonstrate the efficacy of low-dose CBD and Δ9-THC combined and that CBD exerts its effects, at least in part, through 5-HT1A receptors. These results could address drug-resistance while providing insight into CBD\'s mechanism of action, laying the groundwork for further testing of cannabinoids as anticonvulsants.
摘要：
大麻素在抗药性癫痫治疗中显示出潜力；然而，我们缺乏使用哪种大麻素的知识，给药,以及它们的药理靶点。这项研究调查了（i）单独使用大麻二酚（CBD）和（ii）与Delta-9四氢大麻酚（Δ9-THC）联合使用的抗惊厥作用，以及（iii）5-羟色胺（5-HT）1A受体在CBD作用机制中的作用。缉获活动,由4-氨基吡啶诱导，通过在小鼠脑切片的皮质层2/3中的细胞外场记录来测量。评估了10、30和100μMCBD单独和与Δ9-THC组合的抗惊厥作用。为了检查CBD的作用机制，在评估CBD的效果之前，用5-HT1A受体拮抗剂预处理切片。仅≥30µMCBD的量具有显着的抗惊厥作用，而10µMCBD则没有。然而,10µMCBD与低剂量Δ9-THC（20：3比例）的组合显示出比单独使用植物大麻素明显更大的抗惊厥作用。此外，在CBD应用前阻断5-HT1A受体显著消除了CBD的作用。因此，我们的结果表明低剂量CBD和Δ9-THC联合的疗效，并且CBD发挥其作用，至少在某种程度上,通过5-HT1A受体。这些结果可以解决耐药性问题，同时提供对CBD作用机制的洞察，为进一步测试大麻素作为抗惊厥药奠定基础。
