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Role and Function of Endocannabinoid System in Major Depressive Disease. 内源性大麻素系统在重度抑郁症中的作用和功能。
Q1 Medicine Pub Date : 2020-12-11 eCollection Date: 2021-06-01 DOI: 10.1159/000511979
Erhan Yarar

The endocannabinoid system (ECS) is a neuromodulator system with a crucial role in CNS and the reaction to endogenous and exogenous compounds and inflammation. Cannabidiol (CBD) is a basic part of the ECS which is the overwhelming causative and/or protective factor of major depressive disease (MDD). CBD interacts with brain-derived neurotropic factor (BDNF) that responds to inflammation, dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis, and many more imbalances in MDD patients for which the ECS is a vital part to analyze, diagnose, and reflect the treatment. The ECS and MDD appear to have strong connections and interactions, so interest in ECS and CBD use in MDD patients is developing as a rescue resort.

内源性大麻素系统(ECS)是一种神经调节系统,在中枢神经系统以及内源性和外源性化合物和炎症反应中起着至关重要的作用。大麻二酚(CBD)是ECS的基本组成部分,是重度抑郁症(MDD)的主要病因和/或保护因素。CBD与脑源性神经营养因子(BDNF)相互作用,BDNF对炎症、下丘脑-垂体-肾上腺(HPA)轴的失调以及MDD患者的许多失衡做出反应,其中ECS是分析、诊断和反映治疗的重要组成部分。ECS和MDD似乎有很强的联系和相互作用,因此在MDD患者中使用ECS和CBD的兴趣正在发展为一种救援手段。
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引用次数: 7
The Use of Cannabis for Medical Purposes in the Arab World. 阿拉伯世界医用大麻的使用。
Q1 Medicine Pub Date : 2020-12-07 eCollection Date: 2021-06-01 DOI: 10.1159/000510824
Bader H Shirah, Mohammed M Ahmed
The legal landscape of cannabis (marijuana) has dramatically changed over the past few years in several countries worldwide. Many patients now have legal access to products derived from cannabis. In the Middle East, Lebanon became the first Arab country to legalize cannabis for medical and industrial use recently in 2020. Other Middle Eastern and Arab countries continue to completely ban the use of cannabis and products derived from cannabis. This article is a call to conduct medical research in the use of cannabis for medical purposes to determine the suitability and need for this substance in the Arab world. Based on these studies, evidence-based recommendations can be made to the highest authorities in the Arab countries for legalization or continued prohibition. As the international use of cannabis is increasing, the Arab countries may consider legalization of the substance to cover the unmet medical need and offer an additional treatment option for certain conditions.
在过去几年中,世界上几个国家的大麻法律环境发生了巨大变化。许多病人现在可以合法获得大麻制品。在中东,黎巴嫩最近于2020年成为第一个将医疗和工业用途大麻合法化的阿拉伯国家。其他中东和阿拉伯国家继续完全禁止使用大麻和大麻制品。这篇文章呼吁对医用大麻的使用进行医学研究,以确定阿拉伯世界对这种物质的适宜性和必要性。在这些研究的基础上,可以向阿拉伯国家的最高当局提出基于证据的建议,使其合法化或继续禁止。随着大麻在国际上的使用日益增加,阿拉伯国家可考虑使该物质合法化,以满足未得到满足的医疗需求,并为某些情况提供额外的治疗选择。
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引用次数: 6
Abstracts - 5th International Medical Cannabis Conference (CannX 2020), Virtual, October 26-28, 2020 摘要-第五届国际医用大麻会议(CannX 2020),虚拟,2020年10月26日至28日
Q1 Medicine Pub Date : 2020-10-22 DOI: 10.1159/000511664
V. Gyarmathy
Scientific Advisory Committee David (Dedi) Meiri Ph.D, Head of Scientific Advisory Board, Assistant Professor, Heads the ‘Laboratory of Cancer Biology and Cannabinoid Research’ Technion, Institute of Technology, Israel Raquel Peyraube M.D., Director of the Diploma Endocannabinology, Cannabis and Cannabinoids, Rosario National University, Uruguay Orit Stolar M.D., Pediatric Neurologist, Assaf Harofeh Medical Center, Israel Yuval (Tuby) Zolotov Ph.D, Senior Research Associate, Regional Alcohol and Drug Abuse Research Center, Ben Gurion University of the Negev, Israel Med Cannabis Cannabinoids 2020;3:132–142 Published online: October 22, 2020 DOI: 10.1159/000511664 Basel · Freiburg · Hartford · Oxford · Bangkok · Dubai · Kuala Lumpur · Melbourne · Mexico City · Moscow · New Delhi · Paris · Shanghai · Tokyo
科学咨询委员会David(Dedi)Meiri博士,科学咨询委员会负责人,助理教授,以色列理工学院癌症生物学和大麻酚研究实验室技术负责人,Raquel Peyrube医学博士,乌拉圭罗萨里奥国立大学大麻和大麻酚内分泌学博士,Assaf Harofeh医疗中心,以色列Yuval(Tuby)Zolotov博士,内盖夫本古里安大学区域酒精和药物滥用研究中心高级研究员,以色列医学大麻类药物2020;3:132–142在线发布时间:2020年10月22日DOI:10.1159/000511664巴塞尔·弗赖堡·哈特福德·牛津·曼谷·迪拜·吉隆坡·墨尔本·墨西哥城·莫斯科·新德里·巴黎·上海·东京
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引用次数: 0
Cannabidiol (CBD) Oil Does Not Display an Entourage Effect in Reducing Cancer Cell Viability in vitro. 大麻二酚(CBD)油在体外降低癌细胞活力方面没有显示随行效应。
Q1 Medicine Pub Date : 2020-09-17 eCollection Date: 2020-12-01 DOI: 10.1159/000510256
Wesley M Raup-Konsavage, Nurgul Carkaci-Salli, Kelly Greenland, Robert Gearhart, Kent E Vrana

Introduction: Several studies have found that cannabinoids, particularly delta-9-tetrahydrocannabinol and cannabidiol (CBD), have the ability to reduce cancer cell viability. An ongoing debate regarding the use of medical Cannabis revolves around the effectiveness of pure compounds versus intact plant material for treatment. Proponents for the use of intact plant material or botanical extracts argue that there is a synergistic effect between the different cannabinoids, terpenoids, and flavonoids; this is commonly referred to as the "entourage effect." Our study was designed to test the validity of the proposed entourage effect in a narrow application using a cancer cell viability model.

Materials and methods: Six cancer cell lines, from 3 different types of human cancer were treated with 10 μM pure CBD or 10 μM CBD from hemp (Cannabis sativa) oil (obtained from 3 different commercial sources) for 48 h, and cell viability was measured with the MTS assay. Dose-response curves were then performed to compare the potencies of pure CBD to CBD oils. CBD concentrations were independently confirmed in the commercial oils, and cannabinoid and terpene composition were also compared.

Results: CBD (10 μM) was able to reduce cell viability in 3 of the 6 cell lines tested, and this was found to be cell line specific and not specific to select cancers. None of the CBD oils tested were able to reduce viability to a greater extent than that of pure CBD. Additionally, dose-response curves found lower IC50 values for pure CBD compared to the most potent CBD oil tested. Interestingly, some oils actually appeared to protect cancer cells from the effects of CBD.

Conclusions: We found that pure CBD was as potent or more potent at reducing cancer cell viability as the most potent oil tested, suggesting that there is no "entourage" effect under these specific in vitro conditions.

几项研究发现,大麻素,特别是德尔塔-9-四氢大麻酚和大麻二酚(CBD),具有降低癌细胞活力的能力。关于医用大麻使用的持续辩论围绕纯化合物与完整植物材料治疗的有效性展开。支持使用完整植物材料或植物提取物的人认为,不同的大麻素、萜类和类黄酮之间存在协同效应;这通常被称为“随从效应”。我们的研究旨在使用癌细胞活力模型在一个狭窄的应用中测试所提出的随行效应的有效性。材料和方法:用10 μM纯CBD或10 μM大麻油(3种不同的商业来源)处理6株3种不同类型人类癌症的癌细胞48 h,用MTS法测定细胞活力。然后进行剂量-反应曲线来比较纯CBD和CBD油的效力。在商业油中独立确认了CBD浓度,并比较了大麻素和萜烯的组成。结果:CBD (10 μM)能够降低6个细胞系中的3个细胞系的细胞活力,并且发现这是细胞系特异性的,而不是特异性的选择癌症。测试的CBD油中没有一种能够比纯CBD油更大程度地降低活力。此外,剂量-反应曲线发现,与测试的最有效的CBD油相比,纯CBD的IC50值更低。有趣的是,一些油实际上似乎可以保护癌细胞免受CBD的影响。结论:我们发现纯CBD在降低癌细胞活力方面与最有效的油一样有效,甚至更有效,这表明在这些特定的体外条件下没有“随从”效应。
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引用次数: 16
Influence of Light Spectra on the Production of Cannabinoids. 光谱对大麻素生成的影响。
Q1 Medicine Pub Date : 2020-09-16 eCollection Date: 2020-12-01 DOI: 10.1159/000510146
Pascal Amrein, Stefan Rinner, Tindaro Pittorino, Joan Espel, David Schmidmayr

In recent years, more attention has been paid to cannabis from both medical and political points of view. This study investigates the influence of 5 different light spectra on the active substance content in THC-poor hemp of the Alessia chemotype II variety. The focus is on comparing conventional growing under metal halide lamps with growing under high-pressure sodium (HPS) vapor lamps with regard to different spectra of LED lighting modules. Growing was carried out in 10 growing boxes under controlled and mostly identical conditions for all boxes. The photoperiod during the vegetative phase was 18 h light and photosynthetic photon flux density ∼520 μmol⋅m-2 s-1. The flowering phase was 12 h light and ∼540 μmol⋅m-2 s-1. During the experiment, CO2, temperature, and humidity were measured and logged. Additionally, weekly measurements of chlorophyll, electric conductivity of the fertilizer, activity measurement (salt content) of the soil, and pH value of the soil were checked. The content of cannabinoids was measured by high-performance liquid chromatography (HPLC). Plant height and growth were monitored during the whole experiment by cameras taking pictures every 30 min and loading them onto a cloud storage platform. Cannabinoid content was measured using HPLC. Plant wet weight was determined at the end of the experiment and showed that plants under the high pressure lamp treatment had less flower weight than those under the LED treatment. In conclusion, it could be shown that certain LED spectra can considerably increase the amount of cannabinoids with respect to conventional illumination (HPS).

近年来,人们从医学和政治角度对大麻给予了更多关注。本研究调查了 5 种不同光谱对阿莱西亚化学型 II 品种的 THC 贫瘠大麻中活性物质含量的影响。重点是比较传统的金属卤化物灯下种植和高压钠(HPS)蒸汽灯下种植与不同光谱的 LED 照明模块。种植在 10 个种植箱中进行,所有种植箱的条件基本相同,且均受到控制。植物生长期的光周期为 18 小时,光合光通量密度为 520 μmol⋅m-2 s-1。开花期为 12 小时光照和 ∼540 μmol⋅m-2 s-1。实验期间,测量并记录二氧化碳、温度和湿度。此外,还每周测量叶绿素、肥料的电导率、土壤的活性测量值(含盐量)和土壤的 pH 值。大麻素的含量通过高效液相色谱法(HPLC)进行测量。在整个实验过程中,摄像机每隔 30 分钟拍摄一次照片,并将照片加载到云存储平台上,以监测植物的高度和生长情况。大麻素含量采用高效液相色谱法测量。实验结束时测定了植物的湿重,结果显示,高压灯处理下的植物花重低于 LED 处理下的植物。总之,与传统照明(HPS)相比,某些 LED 光谱可以显著增加大麻素的含量。
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引用次数: 0
Cannabinoids and COVID-19. 大麻素和COVID-19。
Q1 Medicine Pub Date : 2020-08-19 eCollection Date: 2020-12-01 DOI: 10.1159/000510799
Myriam El Biali, Barbara Broers, Marie Besson, Jules Demeules

Since the endocannabinoid system is involved in immune function, the effect of cannabinoid intake on infectious conditions is questioned for several years and is of particular interest in the COVID 19 pandemia. Some data suggest that the immunomodulatory effect of cannabinoids may affect the course and severity of SARS-CoV-2 infection. Given the large number of cannabinoids consumers in the community, this commentary presents the current knowledge on the potential impact of cannabinoids and endocannabinoids on bacterial and viral infection courses namely SARS-CoV-2 disease. Practical recommendations, which can be drawn from the literature, are given.

由于内源性大麻素系统与免疫功能有关,大麻素摄入对感染状况的影响多年来一直受到质疑,在新冠肺炎疫情中尤为重要。一些数据表明,大麻素的免疫调节作用可能会影响严重急性呼吸系统综合征冠状病毒2型感染的过程和严重程度。鉴于社区中有大量大麻素消费者,本评论介绍了大麻素和内源性大麻素对细菌和病毒感染过程(即严重急性呼吸系统综合征冠状病毒2型疾病)的潜在影响的最新知识。文中给出了一些实用的建议,这些建议可以从文献中得到。
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引用次数: 13
Analysis of Cannabidiol, Δ9-Tetrahydrocannabinol, and Their Acids in CBD Oil/Hemp Oil Products. CBD油/大麻油产品中大麻二酚,Δ9-Tetrahydrocannabinol及其酸的分析。
Q1 Medicine Pub Date : 2020-08-13 eCollection Date: 2020-08-01 DOI: 10.1159/000509550
Mahmoud A ElSohly, Timothy P Murphy, Ikhlas Khan, Larry W Walker, Waseem Gul

Hemp products are readily available and are aggressively marketed for their health and medicinal benefits. Most consumers of these products are interested because of cannabidiol (CBD), which has taken the natural products industry by storm. The CBD and Δ9-tetrahydrocannabinol (Δ9-THC) concentrations in these products are often absent, and even where labeled, the accuracy of the label amounts is often questionable. In order to gain a better understanding of the CBD content, fifty hemp products were analyzed by gas chromatography coupled with mass spectrometry (GC-MS) for CBD, Δ9-THC, tetrahydrocannabinolic acid (Δ9-THCAA), and cannabidiolic acid (CBDA). Δ9-THCAA and CBDA are the natural precursors of Δ9-THC and CBD in the plant material. Decarboxylation to Δ9-THC and CBD is essential to get the total benefit of the neutral cannabinoids. Therefore, analysis for the neutral and acid cannabinoids is important to get a complete picture of the chemical profile of the products. The GC-MS method used for the analysis of these products was developed and validated. A 10-m × 0.18-mm DB-1 (0.4 μ film) column was used for the analysis. The majority of the hemp products were oils, one of the products was hemp butter, one was a concentrated hemp powder capsule, and another was a hemp extract capsule. Most of the products contained less than 0.1% CBD and less than 0.01% Δ9-THC. Three products contained 0.1-1% CBD, and 2 products contained 0.1-0.9% Δ9-THC. All of the samples appeared to be decarboxylated since the CBDA and Δ9-THCAA results were less than 0.001%. The developed method is simple, sensitive, and reproducible for the detection of Δ9-THC, Δ9-THCAA, CBD, and CBDA in CBD oil/hemp products.

大麻产品很容易获得,并积极推销其健康和药用效益。大多数消费者对这些产品感兴趣是因为大麻二酚(CBD),它已经席卷了天然产品行业。这些产品中的CBD和Δ9-tetrahydrocannabinol (Δ9-THC)浓度通常不存在,即使在标记的地方,标记量的准确性也经常值得怀疑。为了更好地了解大麻二酚(CBD)的含量,采用气相色谱-质谱联用(GC-MS)对50种大麻产品进行了CBD、Δ9-THC、四氢大麻酚酸(Δ9-THCAA)和大麻二酚酸(CBDA)的分析。Δ9-THCAA和CBDA是植物材料中Δ9-THC和CBD的天然前体。脱羧到Δ9-THC和CBD是必不可少的,以获得中性大麻素的总利益。因此,对中性和酸性大麻素的分析对于全面了解产品的化学特征是很重要的。建立并验证了用于分析这些产品的GC-MS方法。采用10 m × 0.18 mm DB-1 (0.4 μ膜)色谱柱进行分析。大麻产品以油脂为主,其中一种产品为大麻黄油,一种产品为浓缩大麻粉末胶囊,另一种产品为大麻提取物胶囊。大部分产品CBD含量小于0.1%,小于0.01% Δ9-THC。3个产品CBD含量0.1-1%,2个产品CBD含量0.1-0.9% Δ9-THC。由于CBDA和Δ9-THCAA结果小于0.001%,所有样品似乎都是脱羧的。该方法简便、灵敏、重现性好,可用于CBD油/大麻制品中Δ9-THC、Δ9-THCAA、CBD和CBDA的检测。
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引用次数: 5
Terpenes/Terpenoids in Cannabis: Are They Important? 大麻中的萜烯/萜类:它们重要吗?
Q1 Medicine Pub Date : 2020-08-10 eCollection Date: 2020-08-01 DOI: 10.1159/000509733
Lumír Ondřej Hanuš, Yotam Hod

Cannabis sativa plant has not only cannabinoids as crucial compounds but also the other compounds that play important role as synergistic and/or entourage compound. Cannabis/hemp plant materials and essential oils were analyzed with the help of gas chromatography/mass spectrometry detector for the content of terpenes and terpenoids. The main terpenes/terpenoids and their abundance in the samples were evaluated. Results of this study will be helpful in the next evaluation of these compound in mixture with cannabinoids and their importance in medical treatment.

大麻植物不仅含有作为关键化合物的大麻素,还含有作为协同和/或环境化合物发挥重要作用的其他化合物。利用气相色谱/质谱检测器对大麻/大麻植物材料和精油中萜烯和萜类化合物的含量进行了分析。对样品中的主要萜烯/萜类化合物及其丰度进行了评价。这项研究的结果将有助于下一步评估这些化合物与大麻素的混合物及其在医疗中的重要性。
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引用次数: 53
Delta-9-Tetrahydrocannabinol and Cannabidiol Drug-Drug Interactions. δ-9-四氢大麻酚和大麻二酚的药物相互作用。
Q1 Medicine Pub Date : 2020-07-07 eCollection Date: 2020-08-01 DOI: 10.1159/000507998
Paul T Kocis, Kent E Vrana

Although prescribing information (PI) is often the initial source of information when identifying potential drug-drug interactions, it may only provide a limited number of exemplars or only reference a class of medications without providing any specific medication examples. In the case of medical cannabis and medicinal cannabinoids, this is further complicated by the fact that the increased therapeutic use of marijuana extracts and cannabidiol oil will not have regulatory agency approved PI. The objective of this study was to provide a detailed and comprehensive drug-drug interaction list that is aligned with cannabinoid manufacturer PI. The cannabinoid drug-drug interaction information is listed in this article and online supplementary material as a PRECIPITANT (cannabinoid) medication that either INHIBITS/INDUCES the metabolism or competes for the same SUBSTRATE target (metabolic enzyme) of an OBJECT (OTHER) medication. In addition to a comprehensive list of drug-drug interactions, we also provide a list of 57 prescription medications displaying a narrow therapeutic index that are potentially impacted by concomitant cannabinoid use (whether through prescription use of cannabinoid medications or therapeutic/recreational use of cannabis and its extracts).

虽然处方信息(PI)通常是识别潜在药物间相互作用的初始信息来源,但它可能只提供数量有限的示例,或者只提及一类药物,而不提供任何具体的药物示例。就医用大麻和药用大麻素而言,由于大麻提取物和大麻二酚油的治疗用途不断增加,而监管机构并未批准其 PI,这使得情况更加复杂。本研究的目的是提供一份与大麻素制造商 PI 一致的详细而全面的药物相互作用列表。本文和在线补充材料中列出的大麻素药物-药物相互作用信息是指一种前体(大麻素)药物会阻碍/促进目标(其他)药物的代谢或竞争目标(代谢酶)。除了药物间相互作用的综合清单外,我们还提供了一份 57 种处方药的清单,这些处方药的治疗指数较窄,可能会受到同时使用大麻素的影响(无论是通过处方使用大麻素药物,还是通过治疗/娱乐使用大麻及其提取物)。
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引用次数: 0
Potential Treatment for Overdose with Synthetic Cannabinoids. 过量使用合成大麻素的潜在治疗方法。
Q1 Medicine Pub Date : 2020-03-23 eCollection Date: 2020-08-01 DOI: 10.1159/000506635
Grant Meredith, Michael DeLollis, Mujeeb U Shad
Emergency departments are increasingly reporting overdoses with synthetic cannabinoids (SCs), such as K2 and Spice, presenting not only as agitation, paranoia, anxiety, and confusion, but also medical complications, such as palpitations, hypertension, nausea, vomiting, and seizures [1]. Multiple deaths have also been reported with SC overdoses [2]. One of the reasons for such high level of toxicity with SCs is their potent agonist activity at cannabinoid type-1 (CB1) receptor without any action on the cannabinoid type-2 (CB2) receptor, which further adds to the adverse effect profile of SCs, as CB2 receptors have been shown to neutralize some of the CB1 receptor activation. However, in contrast to SCs, delta-9-tetrahydrocannabinol (THC; primary psychoactive substance in botanical marijuana) is a partial agonist at CB1 and CB2 receptors. We believe that it is the difference between partial and full agonism at CB1 receptors that makes the SCs so much more toxic than botanical marijuana or THC. In addition, SCs have longer half-lives along with active metabolites, whereas THC is primarily metabolized into the inactive metabolite 11-nor-9-carboxy-9-tetrahydrocannabinol (THC-COOH). Additionally, the effects of THC in botanical marijuana may also be modified by the presence of other cannabinoids and terpenes within the plant [3]. Cannabidiol (CBD) is another important psychoactive agent in marijuana (usually present at much lower concentrations than THC), which is neither an agonist nor a partial agonist but modifies CB1 receptor activity via allosteric modulation [1]. It is shown to be nonaddictive and safe as reflected by LD50, which is more than 100 times greater than the oral dose [3]. More importantly, CBD has also been shown to have preliminary evidence in the management of atonic seizures [4], social anxiety [5], and psychosis in patients with Parkinson’s disease [6]. In addition, CBD is the only marijuana agent that has been approved by the FDA to manage treatment-refractory seizures in children. Although it is theoretically plausible that partial agonism with THC may neutralize some of the neurotoxic effects of SCs, CBD represents a safer and more acceptable approach to neutralize toxic effects of SCs due to its nonaddictive potential and selective allosteric modulation of CB1 receptors. In this context, CBD may provide a specific antidote to the neurotoxicity with SCs [7]. More importantly, approval of CBD formulation (i.e., EpidiolexTM) can ensure qualitative and quantitative monitoring by the FDA. Therefore, we propose to explore CBD treatment to manage overdose and toxicity with SCs, which is increasingly recognized as a life-threatening emergency, especially in the emergency settings across the United States.
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引用次数: 4
期刊
Medical Cannabis and Cannabinoids
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