C. elegans as a test system to study relevant compounds that contribute to the specific health-related effects of different cannabis varieties.

Monique van Es-Remers, Jesus Arellano Spadaro, Eefje Poppelaars, Hye Kyong Kim, Marieke van Haaster, Marcel de Wit, Eva ILiopoulou, Marjolein Wildwater, Henrie Korthout
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引用次数: 1

Abstract

Background: The medicinal effects of cannabis varieties on the market cannot be explained solely by the presence of the major cannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Evidence for putative entourage effects caused by other compounds present in cannabis is hard to obtain due to the subjective nature of patient experience data. Caenorhabditis elegans (C. elegans) is an objective test system to identify cannabis compounds involved in claimed health and entourage effects.

Methods: From a medicinal cannabis breeding program by MariPharm BV, the Netherlands a set of 12 varieties were selected both THC rich varieties as well as CBD rich varieties. A consecutive extraction process was applied resulting in a non-polar (cannabinoid-rich) and polar (cannabinoid-poor) extract of each variety. The test model C. elegans was exposed to these extracts in a broad set of bioassays for appetite control, body oscillation, motility, and nervous system function.

Results: Exposing C. elegans to extracts with a high concentration of cannabinoids (> 1 μg/mL) reduces the life span of C. elegans dramatically. Exposing the nematodes to the low-cannabinoid (< 0.005 μg/mL) polar extracts, however, resulted in significant effects with respect to appetite control, body oscillation, motility, and nervous system-related functions in a dose-dependent and variety-dependent manner.

Discussion: C. elegans is a small, transparent organism with a complete nervous system, behavior and is due to its genetic robustness and short life cycle highly suitable to unravel entourage effects of Cannabis compounds. Although C. elegans lacks an obvious CB1 and CB2 receptor it has orthologs of Serotonin and Vanilloid receptor which are also involved in (endo)cannabinoid signaling.

Conclusion: By using C. elegans, we were able to objectively distinguish different effects of different varieties despite the cannabinoid content. C. elegans seems a useful test system for studying entourage effects, for targeted medicinal cannabis breeding programs and product development.

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秀丽隐杆线虫作为一个测试系统来研究相关化合物,有助于不同大麻品种的特定健康影响。
背景:市场上大麻品种的药用作用不能仅仅通过主要大麻素Δ9-tetrahydrocannabinol (THC)和大麻二酚(CBD)的存在来解释。由于患者经验数据的主观性质,很难获得大麻中存在的其他化合物引起的假定伴随效应的证据。秀丽隐杆线虫(秀丽隐杆线虫)是一个客观的测试系统,以确定大麻化合物涉及声称的健康和随从效应。方法:从荷兰MariPharm BV的药用大麻育种项目中,选择了12个富含四氢大麻酚和CBD的品种。连续提取过程应用导致非极性(大麻素丰富)和极性(大麻素贫乏)提取物的每个品种。实验模型秀丽隐杆线虫暴露于这些提取物中,用于食欲控制、身体振荡、运动和神经系统功能的广泛生物测定。结果:秀丽隐杆线虫暴露于高浓度大麻素(> 1 μg/mL)提取物中,可显著降低秀丽隐杆线虫的寿命。然而,将线虫暴露于低大麻素(< 0.005 μg/mL)极性提取物中,在食欲控制、身体振荡、运动和神经系统相关功能方面产生了显著的影响,且呈剂量依赖性和品种依赖性。讨论:秀丽隐杆线虫是一种小型透明的生物,具有完整的神经系统和行为,由于其遗传稳健性和生命周期短,非常适合解开大麻化合物的随行效应。虽然秀丽隐杆线虫缺乏明显的CB1和CB2受体,但它具有5 -羟色胺和香草素受体的同源物,它们也参与(内)大麻素信号传导。结论:采用秀丽隐杆线虫,可以客观地区分不同品种大麻素含量的不同效果。秀丽隐杆线虫似乎是一个有用的测试系统,研究随从效应,有针对性的药用大麻育种计划和产品开发。
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