Pain Management Research Institute, Kolling Institute of Medical Research, Northern Clinical School, University of Sydney at Royal North Shore Hospital, NSW, Australia.
Pain Management Research Institute, Kolling Institute of Medical Research, Northern Clinical School, University of Sydney at Royal North Shore Hospital, NSW, Australia.
Neuropharmacology. 2021 May 15;189:108529. doi: 10.1016/j.neuropharm.2021.108529. Epub 2021 Mar 16.
The psychoactive and non-psychoactive constituents of cannabis, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have synergistic analgesic efficacy in animal models of neuropathic pain when injected systemically. However, the relevance of this preclinical synergy to clinical neuropathic pain studies is unclear because many of the latter use oral administration. We therefore examined the oral effectiveness of these phytocannabinoids and their interactions in a mouse chronic constriction injury (CCI) model of neuropathic pain. THC produced a dose-dependent reduction in mechanical and cold allodynia, but also induced side-effects with similar potency. CBD also reduced allodynia, albeit with lower potency than THC, but did not produce cannabinoid-like side-effects at any dose tested. Combination THC:CBD produced a dose-dependent reduction in allodynia, however, it displayed little to no synergy. Combination THC:CBD produced substantial, synergistic side-effects which increased with the proportion of CBD. These findings demonstrate that oral THC and CBD, alone and in combination, have analgesic efficacy in an animal neuropathic pain model. Unlike prior systemic injection studies, combination THC:CBD lacks analgesic synergy when delivered orally. Furthermore, both THC and combination THC:CBD display a relatively poor therapeutic window when delivered orally. This suggests that CBD provides a safer, albeit lower efficacy, oral treatment for nerve injury induced neuropathic pain than THC-containing preparations. This article is part of the special issue on 'Cannabinoids'.
大麻的精神活性和非精神活性成分，Δ9-四氢大麻酚（THC）和大麻二酚（CBD），当全身注射时，在神经病理性疼痛的动物模型中具有协同的镇痛功效。然而，这种临床前协同作用与临床神经病理性疼痛研究的相关性尚不清楚，因为后者的许多研究都采用口服给药。因此，我们在神经病理性疼痛的慢性缩窄性损伤（CCI）小鼠模型中检查了这些植物大麻素及其相互作用的口服效果。THC 产生了剂量依赖性的机械和冷感觉过敏减轻，但也具有相似效力的副作用。CBD 也减轻了感觉过敏，尽管效力低于 THC，但在测试的任何剂量下都没有产生类大麻素的副作用。组合 THC：CBD 产生了剂量依赖性的感觉过敏减轻，但显示出很少或没有协同作用。组合 THC：CBD 产生了大量的协同副作用，这些副作用随着 CBD 的比例增加而增加。这些发现表明，口服 THC 和 CBD 单独使用和联合使用在动物神经病理性疼痛模型中具有镇痛功效。与先前的全身注射研究不同，口服给予组合 THC：CBD 缺乏镇痛协同作用。此外，口服给予 THC 和组合 THC：CBD 时，均显示出相对较差的治疗窗口。这表明 CBD 提供了一种更安全、但效力较低的治疗神经损伤引起的神经病理性疼痛的口服治疗方法，优于含 THC 的制剂。本文是“大麻素”特刊的一部分。
