Cannabidiol Toxicity Driven by Hydroxyquinone Formation.

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL Chemical Research in Toxicology Pub Date : 2025-02-17 Epub Date: 2025-01-29 DOI:10.1021/acs.chemrestox.4c00448

Metzli I Montero, Pravien S Rajaram, Jose E Zamora Alvarado, Kara E McCloskey, Ryan D Baxter, Roberto C Andresen Eguiluz

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Abstract

Oxidative byproducts of cannabidiol (CBD) are known to be cytotoxic. However, CBD susceptibility to oxidation and resulting toxicity dissolved in two common solvents, ethanol (EtOH) and dimethyl sulfoxide (DMSO), is seldom discussed. Furthermore, CBD products contain a wide range of concentrations, making it challenging to link general health risks associated with CBD cytotoxicity. Here, we report on the effect of CBD and CBD analogues dissolved in EtOH or DMSO at various concentrations. The cells used in these studies were human umbilical vascular endothelial cells (HUVECs). Our findings show significant CBD oxidation to cannabidiol-quinone (CBD-Q) and subsequent cytotoxicity, occurring at 10 μM concentration, regardless of the solution delivery vehicle. Moreover, a new analogue of CBD, cannabidiol-diacetate (CBD-DA), exhibits significantly more stability and reduced toxicity compared with CBD or CBD-Q, respectively. This knowledge is important for determining concentration-dependent health risks of complex cannabinoid mixtures and establishing legal limits.

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羟基醌形成驱动的大麻二酚毒性。

众所周知，大麻二酚（CBD）的氧化副产物具有细胞毒性。然而，CBD对氧化的敏感性及其在两种常见溶剂乙醇（EtOH）和二甲亚砜（DMSO）中溶解的毒性很少被讨论。此外，CBD产品的浓度范围很广，因此很难将与CBD细胞毒性相关的一般健康风险联系起来。在这里，我们报告了CBD和CBD类似物在不同浓度下溶解在EtOH或DMSO中的影响。在这些研究中使用的细胞是人脐血管内皮细胞（HUVECs）。我们的研究结果表明，无论溶液递送载体如何，在10 μM浓度下，CBD氧化为大麻二酚-醌（CBD- q）并随后产生细胞毒性。此外，一种新的CBD类似物，大麻二酚二乙酸酯（CBD- da），与CBD或CBD- q相比，分别表现出更强的稳定性和更低的毒性。这一知识对于确定复杂大麻素混合物的浓度依赖健康风险和建立法律限制是重要的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chemical Research in Toxicology 医学-毒理学

CiteScore

7.90

自引率

7.30%

发文量

215

审稿时长

3.5 months

期刊介绍： Chemical Research in Toxicology publishes Articles, Rapid Reports, Chemical Profiles, Reviews, Perspectives, Letters to the Editor, and ToxWatch on a wide range of topics in Toxicology that inform a chemical and molecular understanding and capacity to predict biological outcomes on the basis of structures and processes. The overarching goal of activities reported in the Journal are to provide knowledge and innovative approaches needed to promote intelligent solutions for human safety and ecosystem preservation. The journal emphasizes insight concerning mechanisms of toxicity over phenomenological observations. It upholds rigorous chemical, physical and mathematical standards for characterization and application of modern techniques.