植物源和合成大麻素对小鼠认知功能和大麻素戒断症状的单一和联合作用。
Single and combined effects of plant-derived and synthetic cannabinoids on cognition and cannabinoid-associated withdrawal signs in mice.
机构信息
Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
出版信息
Br J Pharmacol. 2019 May;176(10):1552-1567. doi: 10.1111/bph.14147. Epub 2018 Mar 1.
BACKGROUND AND PURPOSE
It has been suggested that the non-euphorogenic phytocannabinoid cannabidiol (CBD) can ameliorate adverse effects of Δ -tetrahydrocannabinol (THC). We determined whether CBD ameliorates cognitive deficits and withdrawal signs induced by cannabinoid CB /CB receptor agonists or produces these pharmacological effects on its own.
EXPERIMENTAL APPROACH
The effects of THC or the CB /CB receptor full agonist WIN55212 alone, CBD alone or their combination were tested across a range of doses. Cognitive effects were assessed in C57BL/6 mice in a conditional discrimination task and in the Barnes maze. Cannabinoid withdrawal signs were assessed following precipitated withdrawal by acute administration of the CB receptor antagonist SR141716, the 5-HT receptor antagonist WAY100635, the TRPV1 receptor antagonist capsazepine or the adenosine A receptor antagonist SCH58261.
KEY RESULTS
THC produced significant motor and cognitive impairment in the Barnes maze task, none of which were attenuated by the addition of CBD. CBD alone did not affect cognitive performance. Precipitation of withdrawal signs by SR141716 occurred in mice chronically treated with THC or WIN55,212. These withdrawal signs were not attenuated by addition of chronic CBD. Chronic treatment with CBD alone did not induce withdrawal signs precipitated by SR141716 or WAY100635. Chronic CBD treatment also produced anxiolysis, which was not altered by attempting to precipitate withdrawal-induced anxiety with a range of antagonists.
CONCLUSIONS AND IMPLICATIONS
CBD as a monotherapy may prove to be a safer pharmacological agent, than CB receptor agonists alone or in combination with CBD, for the treatment of several disorders.
LINKED ARTICLES
This article is part of a themed section on 8 European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc.
背景与目的
有研究表明，非致幻型植物大麻素大麻二酚（CBD）可减轻 Δ -四氢大麻酚（THC）的不良反应。我们确定 CBD 是否能改善大麻素 CB / CB 受体激动剂引起的认知障碍和戒断症状，或者其自身是否会产生这些药理作用。
实验方法
我们检测了 THC 或 CB / CB 受体完全激动剂 WIN55212 单独使用、CBD 单独使用或联合使用的一系列剂量的效果。在条件性辨别任务和巴恩斯迷宫中，我们在 C57BL/6 小鼠中评估了认知效应。在使用 CB 受体拮抗剂 SR141716、5-HT 受体拮抗剂 WAY100635、TRPV1 受体拮抗剂辣椒素或腺苷 A 受体拮抗剂 SCH58261 急性给药引发戒断后，评估了大麻素戒断症状。
主要结果
THC 导致巴恩斯迷宫任务中出现显著的运动和认知障碍，而 CBD 的加入并不能减轻这些影响。CBD 单独使用不会影响认知表现。SR141716 引发慢性接受 THC 或 WIN55212 治疗的小鼠出现戒断症状。这些戒断症状并未因 CBD 的加入而减轻。单独慢性使用 CBD 不会引发 SR141716 或 WAY100635 引发的戒断症状。慢性 CBD 治疗还产生了焦虑缓解作用，而用一系列拮抗剂试图引发戒断引起的焦虑时，这种作用并未改变。
结论和意义
与 CB 受体激动剂单独使用或联合使用相比，CBD 作为单一疗法可能是治疗多种疾病更安全的药物。
相关文章
本文是 8 届欧洲大麻素研究研讨会专题的一部分。要查看该部分中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc.html。
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