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Bridging past and present: exploring Cannabis traditions in Armenia through ethnobotanical interviews and bibliographic prospecting.
IF 4.1 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-30 DOI: 10.1186/s42238-025-00259-x
Manica Balant, Teresa Garnatje, Daniel Vitales, Marine Oganesian, Joan Vallès, Nina Stepanyan-Gandilyan, Airy Gras

Background: Cannabis sativa L. (Cannabaceae) has been widely used by humans throughout its history for a variety of purposes (medicinal, alimentary and other uses). Armenia, with its rich cultural history and diverse ecosystems, offers a unique context for ethnobotanical research about traditional uses of Cannabis. The present work aims to study and preserve the local traditional knowledge about Cannabis in Armenia by conducting interviews with informants and through a literature review.

Methods: The first part of the dataset was gathered with ethnobotanical surveys, through questionnaires conducted with 27 informants. The second part of the data was obtained from a comprehensive bibliographic search in English, Armenian and Russian language. Since the data acquisition was different, the quantitative analyses (calculation of the number of use reports and percentages) were performed separately.

Results: During the interviews 52 use reports and 3 vernacular names were recorded, while the bibliographic data from 20 references, provided us with 56 use reports and 17 Cannabis vernacular names, from the 5th century to 2020. Our results indicate that medicinal applications, particularly for human ailments, and fibre use have markedly dwindled, contrasting with earlier epochs. However, the Cannabis seeds continue to be consumed in celebrative and symbolic dishes such as aghandz and tolma.

Conclusions: The recent decline in the medicinal use of Cannabis contrasts with earlier periods when access to pharmacological remedies was limited, and societal views of the plant were more positive. This shift can be partly attributed to the impact of legal restrictions. In contrast, the use of Cannabis seeds for alimentary purposed is importantly maintained nowadays. As medicinal use, fibre use has also declined, largely due to the availability of more competitive modern products. The loss of vernacular names over time, as detected in this study, also reflects the erosion of traditional knowledge, which correlates with diminishing use. Despite the small sample size and limited geographic scope, the combination of two approaches-information from contemporary informants and a systematic bibliographic review-has provided valuable insights into the changes in the traditional use of Cannabis in Armenia, that has not been explored in this way before.

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引用次数: 0
Feasibility pilot of a novel coaching intervention to optimize cannabis use for chronic pain management among Veterans.
IF 4.1 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-25 DOI: 10.1186/s42238-025-00265-z
Kevin F Boehnke, Gabrielle Bowyer, Jenna McAfee, Tristin Smith, Catherine Klida, Vivian Kurtz, Evangelos Litinas, Poonam Purohit, Anne Arewasikporn, Dana Horowitz, Laura Thomas, Jennifer Eckersley, Mia Railing, David A Williams, Daniel J Clauw, Kelley M Kidwell, Amy S B Bohnert, Rachel S Bergmans

Introduction: Chronic pain is common among Veterans, some of whom use cannabis for pain. We conducted a feasibility pilot study of a novel coaching intervention to help Veterans optimize use of medical cannabis products for pain management (NCT06320470).

Methods: The intervention drew from scientific literature, consultation with cannabis experts, Veteran input via a Community Advisory Board, and tenets of motivational interviewing. Participants were Veterans with chronic pain who endorsed current use or interest in using cannabis for pain management. Participants received up to 4 individual coaching sessions via videoconference, spaced approximately 2 weeks apart. We assessed feasibility (adherence, satisfaction, acceptability) and preliminary effects on pain symptoms 14 weeks after baseline. The primary outcome was the Patient Global Impression of Change (PGIC), and exploratory outcomes included domains from the Patient-Reported Outcomes Measurement Information System (PROMIS)-29.

Results: Of 22 enrolled participants, 17 attended 4 coaching sessions, 2 attended 3 sessions, and 2 attended 2 sessions. Among those who completed end of intervention surveys (16/21), 87.5% were very or completely satisfied with the intervention and 81.3% rated coaching as very or extremely helpful. All participants reported improvement on the PGIC, with 63% reporting much or very much improvement. Participants reported statistically significant decreased pain intensity (7.1/10 vs. 5.7/10) and pain interference (T-score 66.3 vs. 61.8), and increased social satisfaction (T-score 41.4 vs. 44.3). Participants noted helpful intervention factors, including co-developing a personalized plan, discussing questions/concerns, and trying different approaches to cannabis-based treatment.

Conclusions: In this feasibility pilot study of coaching on cannabis use for chronic pain among Veterans, participants were satisfied with the intervention and reported clinically significant improvements in pain symptoms. Our results support evaluating this intervention in a larger, efficacy trial.

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引用次数: 0
CBD for pets: navigating quality assurance, safety standards, and marketing strategies.
IF 4.1 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-23 DOI: 10.1186/s42238-024-00257-5
Hannah Rideout, Alasdair J C Cook, Anthony D Whetton

As the human cannabinoid (CBD) market grows, there is an inevitable transfer of the same or similar products into the veterinary sector. Advances in veterinary medicine and care of companion animals has led to extended life expectancy and consequently, there is an increased incidence of age-related chronic conditions that compromise quality of life. CBD products may alleviate these conditions. Research into CBD for companion animal species is on the rise, however, we found that there are no licensed veterinary CBD products available in the market due to a lack of appropriate testing and/or data. Here we outline the data that is available and show that the regulatory, and safety considerations around these products needs further consideration and this encompasses many products currently available on the market. Changes in regulations and further research for quality assurance are paramount to distribution of safe and applicable products for companion animals.

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引用次数: 0
Oral cannabidiol did not impair learning and memory in healthy adults.
IF 4.1 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-23 DOI: 10.1186/s42238-025-00262-2
Hanna H Gebregzi, Joanna S Zeiger, Jeffrey P Smith, Libby Stuyt, Luann Cullen, Jim Carsella, Daniel C Rogers, Jordan Lafebre, Jennah Knalfec, Alfredo Vargas, Moussa M Diawara

Background: The effect of oral Cannabidiol (CBD) on interference during learning and memory (L&M) in healthy human volunteers has not been studied.

Method: A two-arm crossover, randomized, double-blind, placebo-controlled trial was conducted at Colorado State University Pueblo (CSU Pueblo) to evaluate the effects of 246 mg oral CBD on L&M in healthy adults. Among 57 healthy volunteers enrolled, 35 were included in the analyses. For assessment of L&M, Montreal Cognitive Assessment (MOCA) was used to evaluate verbal baseline cognitive function; RAVLT-R tests (List A and List B recalls, Proactive and Retroactive Interference ratios, and Forgetting Speed ratio) were used to evaluate verbal declarative memory; and total prose recall was used to evaluate verbal logical memory. Linear Mixed Models with Bonferroni Corrections were used to compare L&M results between primary outcomes (CBD vs. placebo) and secondary demographic outcomes, with a two-tailed statistical significance of P < 0.05.

Results: CBD administration did not affect any of the dependent variables measured compared to the placebo group. There were no effects of THC, history of CBD use, or sex on CBD's modulation of L&M. However, a highly significant interaction effect between treatment groups (CBD vs. placebo) and age of subjects was observed for the PI ratio (P = 0.008; n = 35).

Conclusions: The results of this study suggest that administration of oral CBD alone does not significantly impair L&M in healthy adults. However, age might influence CBD related modulation of proactive interference during human L&M. Future research involving a larger group of older adults is needed to confirm this potential effect.

Trial registration: The study was approved by the CSU Pueblo IRB, conducted in accordance with the Declaration of Helsinki, and registered with ClinicalTrials.gov (NCT06074172).

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引用次数: 0
Peer-review Blinded Assay Test (P-BAT): a framework for trustless laboratory quality assurance for state-regulated cannabis markets. 同行评议盲法分析测试(P-BAT):国家管制的大麻市场的无信任实验室质量保证框架。
IF 4.1 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-21 DOI: 10.1186/s42238-025-00261-3
Stuart Procter, Grayson L Baird, Jason Iannuccilli

The purpose of laboratory testing in the cannabis industry is to ensure public safety by preventing products that exceed hazardous limits of contaminants from reaching consumers, and to provide consumers with transparent and accurate label information so that they can make informed decisions when purchasing and using products. However, cannabis testing does not exist in a vacuum of incentives-some incentives exist that are in direct conflict with what is best for consumers. For example, cultivators and distributors will prefer to use the services of laboratories that find the highest THC concentrations or lowest contaminant concentrations, regardless of the accuracy of their testing results. Laboratories will, therefore, be incentivized to serve the cultivators and distributors over the end consumer. The present essay proposes a framework for quality assurance that combats these perverse incentives. The following proposed framework called the Peer-review Blinded Assay Test (P-BAT), is a validation process where each laboratory tests products from competing labs and their own lab, but in a blinded fashion to ensure that the label values of said products and the labs that produced said labels, are unknown. This system of blinded self-review and peer-review is designed to be cost-efficient, transparent, nearly self-funded, can be implemented in any state with two or more laboratories, and most importantly, it is trustless-there is no need to trust the behavior of any one actor or laboratory to serve as a "gold standard". While the primary objective of this process is to focus on laboratory performance, it will also highlight other common problems in the industry such as product adulteration by distributors and poor storge practices. Data from P-BAT should be publicly available so consumers can make informed decisions about their purchases based on the quality data derived from P-BAT. Doing so would further incentivize laboratories to serve and be accountable to the end consumer instead of cultivators and distributors.

在大麻工业中进行实验室检测的目的是通过防止超过污染物危险限度的产品接触到消费者,确保公共安全,并向消费者提供透明和准确的标签信息,以便他们在购买和使用产品时作出知情决定。然而,大麻测试并非存在于激励机制的真空中——某些激励机制的存在与消费者的最佳利益直接冲突。例如,种植者和经销商将更愿意使用发现最高四氢大麻酚浓度或最低污染物浓度的实验室的服务,而不管其测试结果的准确性。因此,实验室将被激励为种植者和分销商服务,而不是最终消费者。本文提出了一个质量保证框架,以对抗这些不正当的激励。以下提议的框架称为同行评审盲法分析测试(P-BAT),是一个验证过程,其中每个实验室测试来自竞争实验室和自己实验室的产品,但以盲法的方式确保所述产品和生产所述标签的实验室的标签值是未知的。这种盲目的自我审查和同行审查的系统被设计成具有成本效益,透明,几乎是自费的,可以在任何有两个或更多实验室的州实施,最重要的是,它是不可信的——没有必要相信任何一个参与者或实验室的行为作为“黄金标准”。虽然该流程的主要目标是关注实验室性能,但它也将突出行业中的其他常见问题,如分销商的产品掺假和不良的存储操作。P-BAT的数据应该是公开的,这样消费者就可以根据P-BAT得出的质量数据做出明智的购买决定。这样做将进一步激励实验室服务并对最终消费者负责,而不是对种植者和分销商负责。
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引用次数: 0
Lebanese Cannabis sativa L. extract protects from cisplatin-induced nephrotoxicity in mice by inhibiting podocytes apoptosis. 黎巴嫩大麻提取物通过抑制足细胞凋亡来保护顺铂诱导的小鼠肾毒性。
IF 4.1 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-16 DOI: 10.1186/s42238-025-00260-4
Alia Khalil, Sahar Al Toufaily, Wassim Shebaby, Marissa El Hage, Dima Mroue, Wissam Faour, Mohamad Mroueh

Background: Cisplatin is an anti-cancer drug used to treat a plethora of solid tumors. However, it is associated with dose dependent nephrotoxicity limiting its use as anticancer agent.

Objective: The current study aimed to investigate the nephroprotective effect of native Lebanese Cannabis sativa in both in vitro and in vivo mice model of cisplatin-induced nephrotoxicity.

Methods: Podocytes cell viability was assessed using MTS assay with cisplatin (30µM) in presence or absence of Cannabis oil extract (COE) at 0.5, 1 and 2µg/ml for 24h. Acute renal injury was established in adult female C57BL/6 mice with 20mg/kg, i.p. single dose cisplatin. Mice were divided into control group (vehicle), COE group, cisplatin group and cisplatin plus COE (2.5, 5 and 20mg/kg, i.p.). Animal body weight, serum creatinine, blood urea nitrogen (BUN), and proteinuria were measured.

Results: Cell viability assay and western blot analysis revealed that COE prevented apoptosis induced by cisplatin in cultured immortalized rat podocytes. In addition, in vitro scratch assay demonstrated the ability of COE to promote and restore the migratory capacity of podocytes in cisplatin-treated cells. Interestingly, COE treatment improved urinary and serum parameters characterized by a significant decrease in serum creatinine, urea, and proteinuria at various COE doses. Western blot analysis showed that COE inhibited COX-2 protein induction as well as apoptosis marker production (Bax/Bcl2 ratio) in cisplatin-treated mice when compared to mice treated with cisplatin alone.

Conclusion: Collectively, the aforementioned findings indicate that COE could be a promising approach to protect against cisplatin-induced nephrotoxicity.

背景:顺铂是一种用于治疗大量实体瘤的抗癌药物。然而,它与剂量依赖性肾毒性有关,限制了其作为抗癌剂的使用。目的:研究天然黎巴嫩大麻对体内体外顺铂肾毒性小鼠的肾保护作用。方法:采用MTS法,用顺铂(30µM)在大麻油提取物(COE)浓度为0.5、1和2µg/ml或不含大麻油提取物(COE)的情况下测定足细胞活力24h。顺铂单剂量20mg/kg对成年雌性C57BL/6小鼠造成急性肾损伤。小鼠分为对照组(载体)、COE组、顺铂组和顺铂加COE(2.5、5、20mg/kg, i.p)。测定动物体重、血清肌酐、血尿素氮(BUN)和蛋白尿。结果:细胞活力测定和western blot分析显示,COE可抑制顺铂诱导的永生化大鼠足细胞凋亡。此外,体外划痕实验表明,COE能够促进和恢复顺铂处理细胞足细胞的迁移能力。有趣的是,COE治疗改善了尿和血清参数,其特征是不同剂量的COE显著降低了血清肌酐、尿素和蛋白尿。Western blot分析显示,与单用顺铂处理的小鼠相比,COE抑制顺铂处理小鼠COX-2蛋白的诱导以及凋亡标志物(Bax/Bcl2比值)的产生。结论:综上所述,上述研究结果表明,COE可能是一种有希望的预防顺铂引起的肾毒性的方法。
{"title":"Lebanese Cannabis sativa L. extract protects from cisplatin-induced nephrotoxicity in mice by inhibiting podocytes apoptosis.","authors":"Alia Khalil, Sahar Al Toufaily, Wassim Shebaby, Marissa El Hage, Dima Mroue, Wissam Faour, Mohamad Mroueh","doi":"10.1186/s42238-025-00260-4","DOIUrl":"10.1186/s42238-025-00260-4","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin is an anti-cancer drug used to treat a plethora of solid tumors. However, it is associated with dose dependent nephrotoxicity limiting its use as anticancer agent.</p><p><strong>Objective: </strong>The current study aimed to investigate the nephroprotective effect of native Lebanese Cannabis sativa in both in vitro and in vivo mice model of cisplatin-induced nephrotoxicity.</p><p><strong>Methods: </strong>Podocytes cell viability was assessed using MTS assay with cisplatin (30µM) in presence or absence of Cannabis oil extract (COE) at 0.5, 1 and 2µg/ml for 24h. Acute renal injury was established in adult female C57BL/6 mice with 20mg/kg, i.p. single dose cisplatin. Mice were divided into control group (vehicle), COE group, cisplatin group and cisplatin plus COE (2.5, 5 and 20mg/kg, i.p.). Animal body weight, serum creatinine, blood urea nitrogen (BUN), and proteinuria were measured.</p><p><strong>Results: </strong>Cell viability assay and western blot analysis revealed that COE prevented apoptosis induced by cisplatin in cultured immortalized rat podocytes. In addition, in vitro scratch assay demonstrated the ability of COE to promote and restore the migratory capacity of podocytes in cisplatin-treated cells. Interestingly, COE treatment improved urinary and serum parameters characterized by a significant decrease in serum creatinine, urea, and proteinuria at various COE doses. Western blot analysis showed that COE inhibited COX-2 protein induction as well as apoptosis marker production (Bax/Bcl2 ratio) in cisplatin-treated mice when compared to mice treated with cisplatin alone.</p><p><strong>Conclusion: </strong>Collectively, the aforementioned findings indicate that COE could be a promising approach to protect against cisplatin-induced nephrotoxicity.</p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":"7 1","pages":"3"},"PeriodicalIF":4.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction: Competing Interests. 更正:利益冲突。
IF 4.1 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-06 DOI: 10.1186/s42238-024-00254-8
{"title":"Correction: Competing Interests.","authors":"","doi":"10.1186/s42238-024-00254-8","DOIUrl":"https://doi.org/10.1186/s42238-024-00254-8","url":null,"abstract":"","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":"7 1","pages":"2"},"PeriodicalIF":4.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hypothesized pharmacogenomic and medication influences on tetrahydrocannabinol and cannabidiol metabolism in a cohort of unselected oral cannabis users. 假设药物基因组学和药物对未选择的口服大麻使用者四氢大麻酚和大麻二酚代谢的影响。
IF 4.1 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-04 DOI: 10.1186/s42238-024-00256-6
Jessica A Wright, Linda Huang, Basant E Katamesh, Siddhant Yadav, Abhinav Singla, Ann Vincent

Background: Differences in cannabinoid metabolism and patient responses can arise even with equivalent doses and formulations. Genetic polymorphisms in genes responsible for cannabinoid metabolism and medications that alter CYP450 pathways responsible for metabolism of cannabinoids may account for some of this variability.

Materials and methods: A retrospective chart review was conducted on a cohort of unselected patients who had previously completed pharmacogenomic testing and reported oral cannabis use, as defined as "oral" or "by mouth" route of administration. The objective was to identify atypical variants and medications in this cohort and formulate a hypothesis on how these variables influence the metabolism of Tetrahydrocannabinol (THC) and Cannabidiol (CBD).

Results: Oral cannabis use was confirmed in 71 patients, with an average age of 68.5 years, and primarily white women. Of the 71 patients, 10 had no atypical variants; 31 had atypical variants in CYP2C9; 37 had atypical variants in CYP2C19; 6 had atypical variants in CYP3A4; and 15 had atypical variants in CYP3A5. Of the 71 patients, 5 were taking medications that could interact with THC, and 8 were taking medications that could interact with CBD.

Conclusion: The results this study reveal the spectrum of hypothesized alterations in THC and CBD metabolism due to atypical genetic variants and medications. The absence of published clinical outcomes in this field renders it challenging to estimate clinical significance of these findings. Until such data become available, clinicians should remain aware of the possibility that atypical variants and medications may impact patients' responses to THC and CBD.

背景:即使相同的剂量和配方,大麻素代谢和患者反应也可能出现差异。负责大麻素代谢的基因的遗传多态性和改变负责大麻素代谢的CYP450通路的药物可能是这种变异的部分原因。材料和方法:对一组未选择的患者进行回顾性图表回顾,这些患者先前已完成药物基因组学测试并报告口服大麻使用,定义为“口服”或“口服”给药途径。目的是确定该队列中的非典型变异和药物,并就这些变量如何影响四氢大麻酚(THC)和大麻二酚(CBD)的代谢制定假设。结果:71例患者被证实使用过口服大麻,平均年龄68.5岁,主要是白人女性。71例患者中,10例无非典型变异;31例CYP2C9有非典型变异;CYP2C19不典型变异37例;6例CYP3A4有非典型变异;15例CYP3A5有非典型变异。在71名患者中,5名患者服用的药物可能与四氢大麻酚相互作用,8名患者服用的药物可能与CBD相互作用。结论:本研究结果揭示了非典型遗传变异和药物导致的四氢大麻酚和CBD代谢的假设改变谱。该领域缺乏已发表的临床结果,因此很难估计这些发现的临床意义。在获得这些数据之前,临床医生应该意识到非典型变异和药物可能会影响患者对THC和CBD的反应。
{"title":"Hypothesized pharmacogenomic and medication influences on tetrahydrocannabinol and cannabidiol metabolism in a cohort of unselected oral cannabis users.","authors":"Jessica A Wright, Linda Huang, Basant E Katamesh, Siddhant Yadav, Abhinav Singla, Ann Vincent","doi":"10.1186/s42238-024-00256-6","DOIUrl":"10.1186/s42238-024-00256-6","url":null,"abstract":"<p><strong>Background: </strong>Differences in cannabinoid metabolism and patient responses can arise even with equivalent doses and formulations. Genetic polymorphisms in genes responsible for cannabinoid metabolism and medications that alter CYP450 pathways responsible for metabolism of cannabinoids may account for some of this variability.</p><p><strong>Materials and methods: </strong>A retrospective chart review was conducted on a cohort of unselected patients who had previously completed pharmacogenomic testing and reported oral cannabis use, as defined as \"oral\" or \"by mouth\" route of administration. The objective was to identify atypical variants and medications in this cohort and formulate a hypothesis on how these variables influence the metabolism of Tetrahydrocannabinol (THC) and Cannabidiol (CBD).</p><p><strong>Results: </strong>Oral cannabis use was confirmed in 71 patients, with an average age of 68.5 years, and primarily white women. Of the 71 patients, 10 had no atypical variants; 31 had atypical variants in CYP2C9; 37 had atypical variants in CYP2C19; 6 had atypical variants in CYP3A4; and 15 had atypical variants in CYP3A5. Of the 71 patients, 5 were taking medications that could interact with THC, and 8 were taking medications that could interact with CBD.</p><p><strong>Conclusion: </strong>The results this study reveal the spectrum of hypothesized alterations in THC and CBD metabolism due to atypical genetic variants and medications. The absence of published clinical outcomes in this field renders it challenging to estimate clinical significance of these findings. Until such data become available, clinicians should remain aware of the possibility that atypical variants and medications may impact patients' responses to THC and CBD.</p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":"7 1","pages":"1"},"PeriodicalIF":4.1,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluation of the metabolic activity, angiogenic impacts, and GSK-3β signaling of the synthetic cannabinoid MMB-2201 on human cerebral microvascular endothelial cells. 合成大麻素MMB-2201对人脑微血管内皮细胞的代谢活性、血管生成影响和GSK-3β信号传导的评价
IF 4.1 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-20 DOI: 10.1186/s42238-024-00255-7
Laith Naser Al-Eitan, Saif Zuhair Alahmad, Sufyan Ali Ajeen, Ahmad Younis Altawil, Iliya Yacoub Khair, Hana Salah Abu Kharmah, Mansour Abdullah Alghamdi

Angiogenesis is an intrinsic physiological process involving the formation of new capillaries from existing ones. Synthetic cannabinoids refer to a class of human-made chemicals that are primarily designed to mimic the effects of delta-9-tetrahydrocannabinol, the primary psychoactive compound in cannabis. Studies investigating the association between synthetic cannabinoids and cellular reactions are limited, and the available scientific evidence is insufficient. Consequently, the primary goal was to examine the effects of the synthetic cannabinoid MDMB-2201 on brain angiogenesis in vitro to provide a comprehensive analysis of MMB-2201's potential therapeutic or adverse effects on vascular development and related health conditions. Human Cerebral Microvascular Endothelial Cells (HBEC-5i) were incubated with MMB-2201, and their metabolic activity, migration rate, and tubular structure formation were examined. Expression levels of several angiogenesis-related proteins such as vascular endothelial growth factor (VEGF), Angiopoietin-1 (ANG-1), and Angiopoietin-2 (ANG-2) were assessed using western blot, ELISA, and real-time PCR. Furthermore, the phosphorylation of glycogen synthase kinase 3 beta (GSK-3β) at Ser9 induced by MMB-2201 was evaluated. HBEC-5i cells showed a significant increase in metabolic rate, enhanced migration, and sprouting of brain endothelial cells. Moreover, there was a noticeable increase in the mRNA and protein levels of VEGF, ANG-1, and ANG-2, as well as in the phosphorylation rate of GSK-3β at Ser9. This study paves the way for a novel pharmacological approach to addressing various angiogenesis-related diseases by targeting cannabinoid receptor type-1. Further exploration using different antagonists or agonists of cannabinoid receptors, depending on the specific characteristics of the disorders, may be necessary.

血管生成是一个内在的生理过程,涉及到从现有的毛细血管形成新的毛细血管。合成大麻素指的是一类人造化学物质,主要用于模仿大麻中主要的精神活性化合物-9-四氢大麻酚的作用。研究合成大麻素和细胞反应之间的关系是有限的,现有的科学证据是不足的。因此,本研究的主要目的是研究合成大麻素MDMB-2201对体外脑血管生成的影响,以全面分析MMB-2201对血管发育和相关健康状况的潜在治疗或不良影响。人脑微血管内皮细胞(HBEC-5i)与MMB-2201孵育,检测其代谢活性、迁移率和管状结构形成。采用western blot、ELISA和real-time PCR检测几种血管生成相关蛋白如血管内皮生长因子(VEGF)、血管生成素-1 (ang1)和血管生成素-2 (ang2)的表达水平。此外,我们还评估了MMB-2201诱导糖原合成酶激酶3β (GSK-3β) Ser9位点的磷酸化。HBEC-5i细胞代谢率显著提高,迁移能力增强,脑内皮细胞萌发。VEGF、ANG-1、ANG-2 mRNA和蛋白水平显著升高,GSK-3β Ser9位点磷酸化率显著升高。本研究为通过靶向大麻素受体1型来解决各种血管生成相关疾病的新药理学方法铺平了道路。根据疾病的具体特征,进一步探索使用大麻素受体的不同拮抗剂或激动剂可能是必要的。
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引用次数: 0
Is nitrogen-modified atmosphere packaging a tool for retention of volatile terpenes and cannabinoids in stored Cannabis sativa inflorescence? 氮修饰大气包装是一种工具,用于保留挥发性萜烯和大麻素在储存的大麻花序?
IF 4.1 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-20 DOI: 10.1186/s42238-024-00253-9
Luke L MacLaughlin, Mason T MacDonald

Modified atmosphere packaging (MAP) alters the gaseous composition of air surrounding packaged goods to prevent deleterious oxidation associated reactions. MAP has been adopted for the storage of cannabis, though a recent study revealed little difference in terpene content under MAP conditions. Questions regarding its efficacy for preservation of high value compounds like terpenes and cannabinoids lost during postharvest storage remain. The goal of this research is to determine weather N2 MAP preserves high value compounds of cannabis during its postharvest storage. This experiment followed a completed randomized block design. There were two factors of interest. The first was storage atmosphere (atmospheric or N2 MAP). The second was storage duration (18, 46, or 74 days). The experiment was then blocked by cannabis chemovar using 5 different chemovars. The concentration of 17 cannabinoids was evaluated through UPLC-UV and 61 volatile terpene compounds through GC-MS. Concentrations were compared over time and between storage treatments. There were no significant differences in total cannabinoids and volatile terpene compounds over time or between storage treatments. Individual cannabinoids Δ9-THC, CBG, CBNA, CBC, THCV, and THCVA all increased during storage time while THCA decreased. CBG and THCV only increased under MAP storage. Individual aromatics limonene, β-pinene, α-pinene, camphene, and terpinolene all only decreased during storage under N2 MAP. Only caryophyllene oxide and α-humulene increased under N2 MAP storage. β-Myrcene decreased under atmospheric storage, but not under N2 MAP. While N2 MAP had no effect on the preservation of total cannabinoids and aromatics during storage, it did influence several individual compounds. CBG, THCV, and α-humulene all increased under N2 MAP. N2 MAP also maintained the concentration β-myrcene over time, though the preservation of β-myrcene was offset by a decrease limonene. Overall, N2 MAP was not needed for preservation of most high value compounds but did have an effect of some compounds with reputed therapeutic benefits.

气调包装(MAP)改变被包装货物周围空气的气体组成,以防止有害的氧化相关反应。MAP已被用于大麻的储存,尽管最近的一项研究表明,在MAP条件下萜烯含量几乎没有差异。关于其在保存高价值化合物如萜烯和大麻素在采收后储存过程中丢失的功效的问题仍然存在。本研究的目的是确定N2 MAP在其采后储存期间是否保留大麻的高价值化合物。本实验采用完全随机区组设计。有两个令人感兴趣的因素。第一种是储存气氛(atmospheric或N2 MAP)。第二个是储存时间(18、46或74天)。然后用5种不同的大麻化学药物阻断实验。UPLC-UV法测定17种大麻素的浓度,GC-MS法测定61种挥发性萜化合物的浓度。浓度随时间和不同储存处理之间的比较。总大麻素和挥发性萜烯化合物在不同时间或不同储存处理之间没有显著差异。各大麻素Δ9-THC、CBG、CBNA、CBC、THCV和THCVA均随贮藏时间增加而THCA降低。CBG和THCV仅在MAP储存下增加。在N2 MAP条件下,柠檬烯、β-蒎烯、α-蒎烯、莰烯和萜烯等单体芳香族化合物在贮藏过程中均呈下降趋势。只有石竹烯氧化物和α-葎草烯在N2 MAP下增加。常压下β-月桂烯含量下降,N2 MAP下无明显变化。虽然N2 MAP对储存过程中总大麻素和芳烃的保存没有影响,但它确实影响了几个单独的化合物。N2 MAP下CBG、THCV、α-葎草烯均升高。随着时间的推移,N2 MAP也保持β-月桂烯的浓度,尽管β-月桂烯的保存被柠檬烯的减少所抵消。总的来说,N2 MAP不需要用于保存大多数高价值化合物,但确实对某些具有公认治疗益处的化合物有影响。
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引用次数: 0
期刊
Journal of cannabis research
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