Cannabidiol-Δ9-tetrahydrocannabinol interactions on acute pain and locomotor activity

Cannabidiol-Δ9-tetrahydrocannabinol interactions on acute pain and locomotor activity
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DOI:
10.1016/j.drugalcdep.2017.01.046
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发表时间:
2017-06-01
影响因子:
4.2
通讯作者:
Craft, Rebecca M.
Craft, Rebecca M.
中科院分区:
医学2区
文献类型:
--
作者:
Britch, Stevie C.;Wiley, Jenny L.;Craft, Rebecca M.

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背景:以前的研究表明,大麻二酚(CBD)可能会加强或拮抗δ(9)-四氢大麻酚(THC)的作用。目前的研究探讨了性别差异CBD调制THC诱导的抗伤害性,hypolocomotion,和metabolis.Methods:在实验1中,CBD(0,10或30毫克/公斤)THC(0,1.8,3.2,5.6或10毫克/公斤)前15分钟,和大鼠进行了测试THC注射后15-360分钟的抗伤害性和运动。在实验2和3中,CBD在THC前13小时或15分钟给予(30 mg/kg)(1.8mg/kg);在THC注射后30-480分钟测试大鼠的抗伤害感受和运动(实验2),或在THC注射后30-360分钟采集血清样品以检查CBD对THC代谢的调节结果:在实验1中,单独的CBD不产生抗伤害性感受作用,而在THC注射后4-6 h增强THC诱导的爪压力,但不产生尾部撤回抗伤害性感受。CBD单独在注射后6小时增加运动活性,但在较低的THC剂量下,在THC注射后4-6小时增强THC诱导的低运动。CBD-THC相互作用没有性别差异。实验2和实验3中,在THC注射前13 h或15 min给予CBD,CBD对THC的镇痛作用无明显增强作用,但CBD对THC代谢的抑制作用女性大于男性。然而,这些影响很小,并且在不同的实验中不一致。CBD抑制THC代谢以及其他机制可能有助于CBD-THC对行为的相互作用。
Background: Previous studies suggest that cannabidiol (CBD) may potentiate or antagonize Delta(9)-tetrahydrocannabinol's (THC) effects. The current study examined sex differences in CBD modulation of THC-induced antinociception, hypolocomotion, and metabolism.Methods: In Experiment 1, CBD (0, 10 or 30 mg/kg) was administered 15 min before THC (0, 1.8, 3.2, 5.6 or 10 mg/kg), and rats were tested for antinociception and locomotion 15-360 min post-THC injection. In Experiments 2 and 3, CBD (30 mg/kg) was administered 13 h or 15 min before THC (1.8 mg/kg); rats were tested for antinociception and locomotion 30-480 min post-THC injection (Experiment 2), or serum samples were taken 30-360 min post-THC injection to examine CBD modulation of THC metabolism (Experiment 3).Results: In Experiment 1, CBD alone produced no antinociceptive effects, while enhancing THC-induced paw pressure but not tail withdrawal antinociception 4-6 h post-THC injection. CBD alone increased locomotor activity at 6 h post-injection, but enhanced THC-induced hypolocomotion 4-6 h post-THC injection, at lower THC doses. There were no sex differences in CBD-THC interactions. In Experiments 2 and 3, CBD did not significantly enhance THC's effects when CBD was administered 13 h or 15 min before THC; however, CBD inhibited THC metabolism, and this effect was greater in females than males.Conclusions: These results suggest that CBD may enhance THC's antinociceptive and hypolocomotive effects, primarily prolonging THC's duration of action; however, these effects were small and inconsistent across experiments. CBD inhibition of THC metabolism as well other mechanisms likely contribute to CBD-THC interactions on behavior.