首页 > 最新文献

Medical Cannabis and Cannabinoids最新文献

英文 中文
Cannabis and Anxiety: A Critical Review 大麻与焦虑:批判性评论
Q1 Medicine Pub Date : 2024-02-23 DOI: 10.1159/000534855
Alexander Beletsky, Cherry Liu, Bryson Lochte, Nebiyou K. Samuel, Igor Grant
Abstract Introduction Cannabis has been reported to have both anxiogenic and anxiolytic effects. Habitual cannabis use has been associated with anxiety disorders (AD). The causal pathways and mechanisms underlying the association between cannabis use (CU)/cannabis use disorder (CUD) and anxiety remain unclear. We examined the literature via a systematic review to investigate the link between cannabis and anxiety. The hypotheses studied include causality, the common factor theory, and the self-medication hypothesis. Methods Critical systematic review of published literature examining the relationship of CU/CUD to AD or state-anxiety, including case reports, literature reviews, observational studies, and preclinical and clinical studies. A systematic MEDline search was conducted of terms including: [anxiety], [anxiogenic], [anxiolytic], [PTSD], [OCD], [GAD], [cannabis], [marijuana], [tetrahydrocannabinol], [THC]. Results While several case-control and cohort studies have reported no correlation between CU/CUD and AD or state anxiety (N = 5), other cross-sectional, and longitudinal studies report significant relationships (N = 20). Meta-analysis supports anxiety correlating with CU (N = 15 studies, OR = 1.24, 95% CI: 1.06–1.45, p = 0.006) or CUD (N = 13 studies, OR = 1.68, 95% CI: 1.23–2.31, p = 0.001). PATH analysis identifies the self-medication hypothesis (N = 8) as the model that best explains the association between CU/CUD and AD or state-anxiety. Despite the support of multiple large cohort studies, causal interpretations (N = 17) are less plausible, while the common factor theory (N = 5), stress-misattribution hypothesis, and reciprocal feedback theory lack substantial evidential support. Conclusion The association between cannabis and anxiety is best explained by anxiety predisposing individuals toward CU as a method of self-medication. A causal relationship in which CU causes AD incidence is less likely despite multiple longitudinal studies suggesting so.
摘要 导言 据报道,大麻具有致焦虑和抗焦虑作用。习惯性使用大麻与焦虑症(AD)有关。大麻使用(CU)/大麻使用障碍(CUD)与焦虑之间的因果途径和机制仍不清楚。我们通过系统性综述研究了大麻与焦虑之间的联系。研究的假设包括因果关系、共同因素理论和自我治疗假设。方法 对已发表的研究 CU/CUD 与注意力缺失或状态焦虑之间关系的文献进行批判性系统综述,包括病例报告、文献综述、观察性研究以及临床前和临床研究。我们在 MEDline 上进行了系统性检索,检索词包括[焦虑]、[致焦虑]、[抗焦虑]、[创伤后应激障碍]、[强迫症]、[GAD]、[大麻]、[大麻]、[四氢大麻酚]、[THC]。结果 虽然一些病例对照和队列研究报告称,CU/CUD 与注意力缺失症或状态焦虑之间没有相关性(N = 5),但其他横断面和纵向研究报告称两者之间存在显著关系(N = 20)。元分析支持焦虑与 CU(N = 15 项研究,OR = 1.24,95% CI:1.06-1.45,p = 0.006)或 CUD(N = 13 项研究,OR = 1.68,95% CI:1.23-2.31,p = 0.001)相关。PATH 分析表明,自我药疗假说(N = 8)是最能解释 CU/CUD 与注意力缺失或状态焦虑之间关系的模型。尽管有多项大型队列研究的支持,但因果解释(N = 17)的可信度较低,而共同因素理论(N = 5)、压力归因错误假说和相互反馈理论则缺乏实质性证据支持。结论 大麻与焦虑之间的联系最好解释为焦虑使人倾向于将 CU 作为一种自我治疗方法。尽管多项纵向研究表明,CU 导致注意力缺失症发病率的因果关系不太可能存在。
{"title":"Cannabis and Anxiety: A Critical Review","authors":"Alexander Beletsky, Cherry Liu, Bryson Lochte, Nebiyou K. Samuel, Igor Grant","doi":"10.1159/000534855","DOIUrl":"https://doi.org/10.1159/000534855","url":null,"abstract":"Abstract Introduction Cannabis has been reported to have both anxiogenic and anxiolytic effects. Habitual cannabis use has been associated with anxiety disorders (AD). The causal pathways and mechanisms underlying the association between cannabis use (CU)/cannabis use disorder (CUD) and anxiety remain unclear. We examined the literature via a systematic review to investigate the link between cannabis and anxiety. The hypotheses studied include causality, the common factor theory, and the self-medication hypothesis. Methods Critical systematic review of published literature examining the relationship of CU/CUD to AD or state-anxiety, including case reports, literature reviews, observational studies, and preclinical and clinical studies. A systematic MEDline search was conducted of terms including: [anxiety], [anxiogenic], [anxiolytic], [PTSD], [OCD], [GAD], [cannabis], [marijuana], [tetrahydrocannabinol], [THC]. Results While several case-control and cohort studies have reported no correlation between CU/CUD and AD or state anxiety (N = 5), other cross-sectional, and longitudinal studies report significant relationships (N = 20). Meta-analysis supports anxiety correlating with CU (N = 15 studies, OR = 1.24, 95% CI: 1.06–1.45, p = 0.006) or CUD (N = 13 studies, OR = 1.68, 95% CI: 1.23–2.31, p = 0.001). PATH analysis identifies the self-medication hypothesis (N = 8) as the model that best explains the association between CU/CUD and AD or state-anxiety. Despite the support of multiple large cohort studies, causal interpretations (N = 17) are less plausible, while the common factor theory (N = 5), stress-misattribution hypothesis, and reciprocal feedback theory lack substantial evidential support. Conclusion The association between cannabis and anxiety is best explained by anxiety predisposing individuals toward CU as a method of self-medication. A causal relationship in which CU causes AD incidence is less likely despite multiple longitudinal studies suggesting so.","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"35 1","pages":"19 - 30"},"PeriodicalIF":0.0,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139957437","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
Erratum. 勘误。
Q1 Medicine Pub Date : 2024-02-22 eCollection Date: 2024-01-01 DOI: 10.1159/000537825

[This corrects the article DOI: 10.1159/000534044.].

[此处更正了文章 DOI:10.1159/000534044]。
{"title":"Erratum.","authors":"","doi":"10.1159/000537825","DOIUrl":"https://doi.org/10.1159/000537825","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1159/000534044.].</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"7 1","pages":"31-33"},"PeriodicalIF":0.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11021816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867504","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
Observational Analysis of the Influence of Medical Marijuana Use on Quality of Life in Patients. 使用医用大麻对患者生活质量影响的观察分析。
Q1 Medicine Pub Date : 2024-02-20 eCollection Date: 2024-01-01 DOI: 10.1159/000536591
Mark D Kelley, Marwah Obaid, Edward M Miller, Marla Bowie, Zachary S Heeter

Introduction: A significant gap exists in the understanding and utilization of medical marijuana and its effects on a patient's quality of life. This is largely attributed to Cannabis' sp. Schedule 1 classification, which has impeded the scientific investigation of its effects on the endocannabinoid system (ECS) and quality of life. Additionally, conflicting results from previous studies highlight the need for more research to provide guidance to both patients and clinicians regarding the therapeutic potential of medical marijuana.

Methods: Patients over 18 years of age who were members of the Pennsylvania Medical Marijuana Program (PAMMP) were recruited from regulated Pennsylvania medical marijuana dispensaries. Eligible patients were enrolled through informed consent, following a study design that received approval from the LECOM Institutional Review Board (IRB). Over 90 days, participants were remotely administered an electronic survey every 30 days to collect medical marijuana use patterns and assess changes in quality of life.

Results: Of the 103 participants who completed the study, significant improvements were observed in physical and social functioning, emotional well-being, and energy levels within the first 30 days. Participants reported significant decreases in emotional limitations, fatigue, and pain levels. Notably, participants who used inhaled or vaped products (defined as vape cartridges and concentrates) were younger and exhibited a significantly higher increase in emotional well-being scores compared to those who used flower products (defined as dry leaf only). Participants who consumed medical marijuana for opioid use demonstrated significantly higher THC consumption compared to those seeking treatment for anxiety, chronic pain, or inflammatory bowel disease (IBD). Improvements in the first 30 days also remained constant for the remainder of the study.

Discussion: This study contributed valuable insights into the effects of medical marijuana on quality of life and highlighted potential benefits associated with its use. Moreover, ongoing research aims to assess the observed sustained improvements beyond 90 days, investigating potential long-term trends. While further research is needed to explore the underlying mechanisms of action and long-term effects of medical marijuana, clinicians and patients can gain a better understanding of medical marijuana's therapeutic potential, enabling more informed decisions regarding its use in clinical settings.

导言:在了解和利用医用大麻及其对患者生活质量的影响方面存在着巨大差距。这主要归因于大麻的附表 1 分类,该分类阻碍了对其对内源性大麻素系统 (ECS) 和生活质量影响的科学研究。此外,以往的研究结果相互矛盾,因此需要开展更多研究,为患者和临床医生提供有关医用大麻治疗潜力的指导:从宾夕法尼亚州受监管的医用大麻药房招募年满 18 周岁且属于宾夕法尼亚州医用大麻计划 (PAMMP) 成员的患者。符合条件的患者在知情同意的情况下注册,研究设计获得了 LECOM 机构审查委员会 (IRB) 的批准。在 90 天内,参与者每 30 天接受一次远程电子调查,以收集医用大麻使用模式并评估生活质量的变化:在完成研究的 103 名参与者中,头 30 天内身体和社会功能、情绪健康和精力水平都有显著改善。参与者报告称,情绪限制、疲劳和疼痛程度明显减轻。值得注意的是,与使用鲜花产品(仅指干叶)的参与者相比,使用吸入或熏吸产品(指熏吸筒和浓缩液)的参与者更年轻,其情绪健康评分的增幅也明显更高。与那些因焦虑、慢性疼痛或炎症性肠病(IBD)而寻求治疗的人相比,因使用阿片类药物而吸食医用大麻的参与者的四氢大麻酚消费量明显更高。在研究的剩余时间里,前 30 天的改善情况也保持不变:这项研究为了解医用大麻对生活质量的影响提供了宝贵的见解,并强调了使用大麻的潜在益处。此外,正在进行的研究旨在评估观察到的 90 天后的持续改善情况,调查潜在的长期趋势。虽然还需要进一步的研究来探索医用大麻的潜在作用机制和长期效果,但临床医生和患者可以更好地了解医用大麻的治疗潜力,从而就其在临床环境中的使用做出更明智的决定。
{"title":"Observational Analysis of the Influence of Medical Marijuana Use on Quality of Life in Patients.","authors":"Mark D Kelley, Marwah Obaid, Edward M Miller, Marla Bowie, Zachary S Heeter","doi":"10.1159/000536591","DOIUrl":"10.1159/000536591","url":null,"abstract":"<p><strong>Introduction: </strong>A significant gap exists in the understanding and utilization of medical marijuana and its effects on a patient's quality of life. This is largely attributed to <i>Cannabis'</i> sp. Schedule 1 classification, which has impeded the scientific investigation of its effects on the endocannabinoid system (ECS) and quality of life. Additionally, conflicting results from previous studies highlight the need for more research to provide guidance to both patients and clinicians regarding the therapeutic potential of medical marijuana.</p><p><strong>Methods: </strong>Patients over 18 years of age who were members of the Pennsylvania Medical Marijuana Program (PAMMP) were recruited from regulated Pennsylvania medical marijuana dispensaries. Eligible patients were enrolled through informed consent, following a study design that received approval from the LECOM Institutional Review Board (IRB). Over 90 days, participants were remotely administered an electronic survey every 30 days to collect medical marijuana use patterns and assess changes in quality of life.</p><p><strong>Results: </strong>Of the 103 participants who completed the study, significant improvements were observed in physical and social functioning, emotional well-being, and energy levels within the first 30 days. Participants reported significant decreases in emotional limitations, fatigue, and pain levels. Notably, participants who used inhaled or vaped products (defined as vape cartridges and concentrates) were younger and exhibited a significantly higher increase in emotional well-being scores compared to those who used flower products (defined as dry leaf only). Participants who consumed medical marijuana for opioid use demonstrated significantly higher THC consumption compared to those seeking treatment for anxiety, chronic pain, or inflammatory bowel disease (IBD). Improvements in the first 30 days also remained constant for the remainder of the study.</p><p><strong>Discussion: </strong>This study contributed valuable insights into the effects of medical marijuana on quality of life and highlighted potential benefits associated with its use. Moreover, ongoing research aims to assess the observed sustained improvements beyond 90 days, investigating potential long-term trends. While further research is needed to explore the underlying mechanisms of action and long-term effects of medical marijuana, clinicians and patients can gain a better understanding of medical marijuana's therapeutic potential, enabling more informed decisions regarding its use in clinical settings.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"7 1","pages":"44-50"},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10948168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140158469","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
Dispensaries and Medical Marijuana Certifications and Indications: Unveiling the Geographic Connections in Pennsylvania, USA. 药房和医用大麻认证及说明:揭开美国宾夕法尼亚州的地理联系。
Q1 Medicine Pub Date : 2024-02-20 eCollection Date: 2024-01-01 DOI: 10.1159/000537841
Annemarie G Hirsch, Eric A Wright, Cara M Nordberg, Joseph DeWalle, Elena L Stains, Amy L Kennalley, Joy Zhang, Lorraine D Tusing, Brian J Piper

Introduction: Pennsylvania opened its first medical marijuana (MMJ) dispensary in 2018. Qualifying conditions include six conditions determined to have no or insufficient evidence to support or refute MMJ effectiveness. We conducted a study to describe MMJ dispensary access in Pennsylvania and to determine whether dispensary proximity was associated with MMJ certifications and community demographics.

Methods: Using data from the Pennsylvania Department of Health, we geocoded MMJ dispensary locations and linked them to US Census Bureau data. We created dispensary access measures from the population-weighted centroid of Zip Code Tabulation Areas (ZCTAs): distance to nearest dispensary and density of dispensaries within a 15-min drive. We evaluated associations between dispensary access and the proportion of adults who received MMJ certification and the proportion of certifications for low evidence conditions (amyotrophic lateral sclerosis, epilepsy, glaucoma, Huntington's disease, opioid use disorder, and Parkinson's disease) using negative binomial modeling, adjusting for community features. To evaluate associations racial and ethnic composition of communities and distance to nearest dispensary, we used logistic regression to estimate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for median income.

Results: Distance and density of MMJ dispensaries were associated with the proportion of the ZCTA population certified and the proportion of certifications for insufficient evidence conditions. Compared to ZCTAs with no dispensary within 15 min, the proportion of adults certified increased by up to 31% and the proportion of certifications for insufficient evidence decreased by up to 22% for ZCTAs with two dispensaries. From 2018 to 2021, the odds of being within five miles of a dispensary was up to 20 times higher in ZCTAs with the highest proportions of individuals who were not White (2019: OR: 20.14, CI: 10.7-37.8) and more than double in ZCTAs with the highest proportion of Hispanic individuals (2018: OR: 2.81, CI: 1.51-5.24), compared to ZCTAs with the lowest proportions.

Conclusions: Greater dispensary access was associated with the proportions of certified residents and certifications for low evidence conditions. Whether these patterns are due to differences in accessibility or demand is unknown. Associations between community demographics and dispensary proximity may indicate MMJ access differences.

导言:宾夕法尼亚州于 2018 年开设了第一家医用大麻(MMJ)药房。符合条件的病症包括六种被确定为没有证据或证据不足以支持或反驳 MMJ 有效性的病症。我们开展了一项研究,以描述宾夕法尼亚州的 MMJ 药房使用情况,并确定药房距离是否与 MMJ 认证和社区人口统计学相关:利用宾夕法尼亚州卫生部的数据,我们对 MMJ 药房位置进行了地理编码,并将其与美国人口普查局的数据相链接。我们根据邮政编码制表区(ZCTA)的人口加权中心点创建了药房访问度量:到最近药房的距离和 15 分钟车程内药房的密度。我们使用负二项模型评估了药房准入与获得 MMJ 证书的成人比例以及低证据病症(肌萎缩侧索硬化症、癫痫、青光眼、亨廷顿氏病、阿片类药物使用障碍和帕金森氏病)认证比例之间的关联,并对社区特征进行了调整。为了评估社区的种族和民族构成与最近药房距离之间的关联,我们使用逻辑回归法估算了几率比(OR)和 95% 置信区间(CI),并对收入中位数进行了调整:结果:MMJ 药房的距离和密度与获得认证的 ZCTA 人口比例和证据不足情况的认证比例相关。与 15 分钟内没有药房的 ZCTA 相比,在有两家药房的 ZCTA 中,获得认证的成人比例最多增加了 31%,证据不足的认证比例最多减少了 22%。从 2018 年到 2021 年,在非白人比例最高的 ZCTA,与比例最低的 ZCTA 相比,距离药房 5 英里以内的几率要高出多达 20 倍(2019 年:OR:20.14,CI:10.7-37.8),在西班牙裔比例最高的 ZCTA,这一几率要高出一倍多(2018 年:OR:2.81,CI:1.51-5.24):更多药房的使用与获得认证的居民比例和低证据病症的认证有关。这些模式是由可及性差异还是需求差异造成的,目前尚不清楚。社区人口统计与药房邻近程度之间的关联可能表明 MMJ 获取方面的差异。
{"title":"Dispensaries and Medical Marijuana Certifications and Indications: Unveiling the Geographic Connections in Pennsylvania, USA.","authors":"Annemarie G Hirsch, Eric A Wright, Cara M Nordberg, Joseph DeWalle, Elena L Stains, Amy L Kennalley, Joy Zhang, Lorraine D Tusing, Brian J Piper","doi":"10.1159/000537841","DOIUrl":"10.1159/000537841","url":null,"abstract":"<p><strong>Introduction: </strong>Pennsylvania opened its first medical marijuana (MMJ) dispensary in 2018. Qualifying conditions include six conditions determined to have no or insufficient evidence to support or refute MMJ effectiveness. We conducted a study to describe MMJ dispensary access in Pennsylvania and to determine whether dispensary proximity was associated with MMJ certifications and community demographics.</p><p><strong>Methods: </strong>Using data from the Pennsylvania Department of Health, we geocoded MMJ dispensary locations and linked them to US Census Bureau data. We created dispensary access measures from the population-weighted centroid of Zip Code Tabulation Areas (ZCTAs): distance to nearest dispensary and density of dispensaries within a 15-min drive. We evaluated associations between dispensary access and the proportion of adults who received MMJ certification and the proportion of certifications for low evidence conditions (amyotrophic lateral sclerosis, epilepsy, glaucoma, Huntington's disease, opioid use disorder, and Parkinson's disease) using negative binomial modeling, adjusting for community features. To evaluate associations racial and ethnic composition of communities and distance to nearest dispensary, we used logistic regression to estimate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for median income.</p><p><strong>Results: </strong>Distance and density of MMJ dispensaries were associated with the proportion of the ZCTA population certified and the proportion of certifications for insufficient evidence conditions. Compared to ZCTAs with no dispensary within 15 min, the proportion of adults certified increased by up to 31% and the proportion of certifications for insufficient evidence decreased by up to 22% for ZCTAs with two dispensaries. From 2018 to 2021, the odds of being within five miles of a dispensary was up to 20 times higher in ZCTAs with the highest proportions of individuals who were not White (2019: OR: 20.14, CI: 10.7-37.8) and more than double in ZCTAs with the highest proportion of Hispanic individuals (2018: OR: 2.81, CI: 1.51-5.24), compared to ZCTAs with the lowest proportions.</p><p><strong>Conclusions: </strong>Greater dispensary access was associated with the proportions of certified residents and certifications for low evidence conditions. Whether these patterns are due to differences in accessibility or demand is unknown. Associations between community demographics and dispensary proximity may indicate MMJ access differences.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"7 1","pages":"34-43"},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10939510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131866","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
Fabrication of Orally Fast Disintegrating Wafer Tablets Containing Cannabis Extract Using Freeze Drying Method 用冷冻干燥法制造含大麻提取物的口服快速崩解片剂
Q1 Medicine Pub Date : 2024-02-20 DOI: 10.1159/000537926
Chaowalit Monton, Poj Kulvanich, Natawat Chankana, Jirapornchai Suksaeree, T. Songsak
Introduction: The development of a novel dosage form for cannabis extract is necessary to improve drug delivery and to also enhance patient convenience.Methods: Orally fast disintegrating wafer tablets containing cannabis extract, which were prepared using the freeze drying technique, were developed in this work. The formulation consisted of several key components: cannabis extract as the active compound, Tween® 80 as a surfactant and solubilizer, gelatin and mannitol as structural components, sucralose as a sweetening agent, and sodium methylparaben and sodium propylparaben as preservatives. Results: The optimized formulation consists of the following ingredients: 5% cannabis extract, 1.25% Tween® 80, 5% gelatin, 88.34% mannitol, 0.2% sucralose, 0.19% sodium methylparaben, and 0.02% sodium propylparaben. The resulting wafer tablets exhibited the following characteristics: a porous structure, an average weight of approximately 200 mg, minimal weight variation (less than 1.4%), slightly acidic pH (pH 5.12), disintegration within 10 s, low moisture content (less than 3%), a Δ9-tetrahydrocannabinol content of approximately 2.8 mg, and a cannabidiol content of approximately 0.9 mg. Additionally, the wafer tablets rapidly dissolved in simulated saliva fluid containing sodium lauryl sulfate. Conclusion: This work succeeded in the fabrication of orally disintegrating wafer tablets containing cannabis extract with desired properties.
导言:开发新型大麻提取物剂型是必要的:有必要开发一种新型的大麻提取物剂型,以改善给药效果,同时为患者提供更多便利:本研究采用冷冻干燥技术开发了含有大麻提取物的口服快速崩解威化片。配方由几种关键成分组成:大麻提取物作为活性化合物,吐温® 80 作为表面活性剂和增溶剂,明胶和甘露醇作为结构成分,三氯蔗糖作为甜味剂,苯甲酸甲酯钠和苯甲酸丙酯钠作为防腐剂。结果:优化配方由以下成分组成:5% 大麻提取物、1.25% 吐温® 80、5% 明胶、88.34% 甘露醇、0.2% 三氯蔗糖、0.19% 苯甲酸钠和 0.02% 苯丙醇钠。制成的威化片具有以下特征:多孔结构,平均重量约为 200 毫克,重量变化极小(小于 1.4%),pH 值呈弱酸性(pH 值为 5.12),10 秒内崩解,水分含量低(小于 3%),Δ9-四氢大麻酚含量约为 2.8 毫克,大麻二酚含量约为 0.9 毫克。此外,威化片还能在含有十二烷基硫酸钠的模拟唾液中迅速溶解。结论这项工作成功地制造出了含有大麻提取物的口腔崩解威化片,并具有所需的特性。
{"title":"Fabrication of Orally Fast Disintegrating Wafer Tablets Containing Cannabis Extract Using Freeze Drying Method","authors":"Chaowalit Monton, Poj Kulvanich, Natawat Chankana, Jirapornchai Suksaeree, T. Songsak","doi":"10.1159/000537926","DOIUrl":"https://doi.org/10.1159/000537926","url":null,"abstract":"Introduction: The development of a novel dosage form for cannabis extract is necessary to improve drug delivery and to also enhance patient convenience.\u0000Methods: Orally fast disintegrating wafer tablets containing cannabis extract, which were prepared using the freeze drying technique, were developed in this work. The formulation consisted of several key components: cannabis extract as the active compound, Tween® 80 as a surfactant and solubilizer, gelatin and mannitol as structural components, sucralose as a sweetening agent, and sodium methylparaben and sodium propylparaben as preservatives. \u0000Results: The optimized formulation consists of the following ingredients: 5% cannabis extract, 1.25% Tween® 80, 5% gelatin, 88.34% mannitol, 0.2% sucralose, 0.19% sodium methylparaben, and 0.02% sodium propylparaben. The resulting wafer tablets exhibited the following characteristics: a porous structure, an average weight of approximately 200 mg, minimal weight variation (less than 1.4%), slightly acidic pH (pH 5.12), disintegration within 10 s, low moisture content (less than 3%), a Δ9-tetrahydrocannabinol content of approximately 2.8 mg, and a cannabidiol content of approximately 0.9 mg. Additionally, the wafer tablets rapidly dissolved in simulated saliva fluid containing sodium lauryl sulfate. \u0000Conclusion: This work succeeded in the fabrication of orally disintegrating wafer tablets containing cannabis extract with desired properties.","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139958226","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
Cannabidiol-Derived Cannabinoids: The Unregulated Designer Drug Market Following the 2018 Farm Bill. 大麻二酚衍生大麻素:2018 年农业法案》出台后不受管制的特制药物市场。
Q1 Medicine Pub Date : 2024-02-13 eCollection Date: 2024-01-01 DOI: 10.1159/000536339
Charles N Zawatsky, Sara Mills-Huffnagle, Corinne M Augusto, Kent E Vrana, Jennifer E Nyland

Background: In this review, we summarize current scientific knowledge on psychoactive cannabinoids synthesized from cannabidiol (CBD) and sold in the semi-legal market established in response to the passage of the US Agriculture Improvement Act of 2018, commonly known as the 2018 Farm Bill. The discussion focuses on recent developments that suggest this unregulated market may be fertile ground for a potential health crisis.

Summary: Current research into CBD-derived cannabinoids is mainly limited to Δ8-tetrahydrocannabinol (Δ8-THC) products, with some recent publications beginning to explore O-acetyl-THC, a term describing the acetate ester of Δ8-THC or Δ9-THC, and its potential pulmonary toxicity. We advance the discussion on the CBD-derived cannabinoid market, shedding light on the introduction and associated dangers of novel cannabinoids, likely produced via fully synthetic routes using sidechain variants of CBD, with purportedly greater agonist activity at the human cannabinoid receptor 1 (as a source of euphorigenic activity) than Δ9-THC. We discuss the expanded incorporation of the acetate ester motif into other THC analogues. We also discuss the lack of regulatory oversight for the production of CBD-derived cannabinoids and the unlabeled presence of under-researched cannabinoids formed as reaction side products in the CBD-derived cannabinoid products being sold. Accordingly, we suggest approaches to monitoring the CBD-derived cannabinoid market and investigating the pharmacology of the cannabinoids being consumed. Finally, important epidemiological findings are discussed and future directions for research are suggested to call investigators to this critically understudied field.

Key messages: The CBD-derived cannabinoid market is growing internationally, and the market has diversified to include potent synthetic cannabinoids. The products sold on this unregulated market are under-researched despite growing availability and consumer interest. Ernest investigation of the pharmacology of these novel cannabinoids and the contents of CBD-derived cannabinoid products is critical for monitoring this potential source of another vaping-related epidemic.

背景:在这篇综述中,我们总结了目前关于由大麻二酚(CBD)合成并在半合法市场上销售的精神活性大麻素的科学知识,这些半合法市场是根据美国 2018 年农业改进法案(通常称为 2018 年农业法案)的通过而建立的。讨论的重点是最近的一些进展,这些进展表明这个不受监管的市场可能是潜在健康危机的沃土。摘要:目前对 CBD 衍生大麻素的研究主要局限于Δ8-四氢大麻酚(Δ8-THC)产品,最近的一些出版物开始探讨 O-乙酰基-THC(描述Δ8-THC 或Δ9-THC 的乙酸酯的术语)及其潜在的肺毒性。我们推进了对 CBD 衍生大麻素市场的讨论,揭示了新型大麻素的引入和相关危险,这些大麻素很可能是通过使用 CBD 侧链变体的全合成路线生产的,据称对人类大麻素受体 1 的激动活性(作为兴奋活性的来源)比 Δ9-THC更高。我们讨论了乙酸酯基团在其他四氢大麻酚类似物中的广泛应用。我们还讨论了 CBD 衍生大麻素生产缺乏监管的问题,以及在销售的 CBD 衍生大麻素产品中存在未经充分研究的大麻素反应副产品。因此,我们建议采取一些方法来监测 CBD 衍生大麻素市场,并调查所消费的大麻素的药理学。最后,我们讨论了重要的流行病学发现,并提出了未来的研究方向,呼吁调查人员关注这一研究严重不足的领域:源自 CBD 的大麻素市场在国际上不断增长,而且市场已经多样化,包括强效合成大麻素。尽管市场上销售的产品越来越多,消费者的兴趣也越来越大,但对这个不受监管的市场上销售的产品的研究却不足。Ernest 对这些新型大麻素的药理学以及 CBD 衍生大麻素产品的成分进行调查,对于监测另一种与吸食大麻有关的流行病的潜在来源至关重要。
{"title":"Cannabidiol-Derived Cannabinoids: The Unregulated Designer Drug Market Following the 2018 Farm Bill.","authors":"Charles N Zawatsky, Sara Mills-Huffnagle, Corinne M Augusto, Kent E Vrana, Jennifer E Nyland","doi":"10.1159/000536339","DOIUrl":"10.1159/000536339","url":null,"abstract":"<p><strong>Background: </strong>In this review, we summarize current scientific knowledge on psychoactive cannabinoids synthesized from cannabidiol (CBD) and sold in the semi-legal market established in response to the passage of the US Agriculture Improvement Act of 2018, commonly known as the 2018 Farm Bill. The discussion focuses on recent developments that suggest this unregulated market may be fertile ground for a potential health crisis.</p><p><strong>Summary: </strong>Current research into CBD-derived cannabinoids is mainly limited to Δ<sup>8</sup>-tetrahydrocannabinol (Δ<sup>8</sup>-THC) products, with some recent publications beginning to explore O-acetyl-THC, a term describing the acetate ester of Δ<sup>8</sup>-THC or Δ<sup>9</sup>-THC, and its potential pulmonary toxicity. We advance the discussion on the CBD-derived cannabinoid market, shedding light on the introduction and associated dangers of novel cannabinoids, likely produced via fully synthetic routes using sidechain variants of CBD, with purportedly greater agonist activity at the human cannabinoid receptor 1 (as a source of euphorigenic activity) than Δ<sup>9</sup>-THC. We discuss the expanded incorporation of the acetate ester motif into other THC analogues. We also discuss the lack of regulatory oversight for the production of CBD-derived cannabinoids and the unlabeled presence of under-researched cannabinoids formed as reaction side products in the CBD-derived cannabinoid products being sold. Accordingly, we suggest approaches to monitoring the CBD-derived cannabinoid market and investigating the pharmacology of the cannabinoids being consumed. Finally, important epidemiological findings are discussed and future directions for research are suggested to call investigators to this critically understudied field.</p><p><strong>Key messages: </strong>The CBD-derived cannabinoid market is growing internationally, and the market has diversified to include potent synthetic cannabinoids. The products sold on this unregulated market are under-researched despite growing availability and consumer interest. Ernest investigation of the pharmacology of these novel cannabinoids and the contents of CBD-derived cannabinoid products is critical for monitoring this potential source of another vaping-related epidemic.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"7 1","pages":"10-18"},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10864014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139729984","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
Pharmacokinetic Variability of Oral Cannabidiol and Its Major Metabolites after Short-Term High-Dose Exposure in Healthy Subjects. 健康受试者短期大剂量暴露后口服大麻二酚及其主要代谢物的药代动力学变异性。
Q1 Medicine Pub Date : 2024-01-29 eCollection Date: 2024-01-01 DOI: 10.1159/000535726
Qingchen Zhang, Philip W Melchert, John S Markowitz

Introduction: Cannabidiol (CBD) is a widely utilized nonpsychoactive cannabinoid available as a prescriptive drug treatment and over-the-counter supplement. In humans, CBD is metabolized and forms the major active metabolite 7-hydroxy-cannabidiol (7-OH-CBD), which is further metabolized to 7-carboxy-cannabidiol (7-COOH-CBD). In the current study, plasma concentrations of CBD, 7-OH-CBD, and 7-COOH-CBD were measured, and the potential influences of sex, race, and body mass index (BMI) on the pharmacokinetic variability were assessed.

Methods: Blood samples from a previously conducted CBD drug interaction study in healthy volunteers (n = 12) were utilized. The subjects received orally administered CBD (Epiodiolex®), 750 mg twice daily for 3 days and a single dose on the 4th day. Nine plasma samples were collected, and plasma concentrations of CBD, 7-OH-CBD, and 7-COOH-CBD were analyzed by LC-MS/MS. Peak plasma concentration (Cmax), time to Cmax (Tmax), area under the curve (AUC), and metabolite-to-parent drug exposure ratios (MPR) were calculated. Statistical analysis was performed to determine the correlations of Cmax, AUC, and MPR of CBD, 7-OH-CBD, and 7-COOH-CBD in different sex, race, BMI, and body weight.

Results: For CBD, the mean Cmax was 389.17 ± 153.23 ng/mL, and the mean AUC was 1,542.19 ± 488.04 ng/mL*h. For 7-OH-CBD, the mean Cmax was 81.35 ± 36.64 ng/mL, the mean AUC was 364.70 ± 105.59 ng/mL*h, and the mean MPR was 0.25 ± 0.07. For 7-COOH-CBD, the mean Cmax was 1,717.33 ± 769.22 ng/mL, the mean AUC was 9,888.42 ± 3,961.47 ng/mL*h, and the mean MPR was 7.11 ± 3.48. For 7-COOH-CBD, a 2.25-fold higher Cmax was observed in female subjects (p = 0.0155) and a 1.97-fold higher AUC for female subjects (p = 0.0285) with the normalization of body weight. A significant linearity (p = 0.0135) of 7-OH-CBD AUC with body weight in females was observed. No significant differences were identified in Cmax, AUC, and PMR with race and BMI.

Conclusion: Observed differences in sex were in agreement with previously reported findings. A larger population pharmacokinetics study is warranted to validate the observed higher Cmax and AUC in females and significant linearity with body weight in females from the current study.

简介:大麻二酚(CBD)是一种广泛使用的非精神活性大麻素,可作为处方药物治疗和非处方补充剂。在人体中,大麻二酚会被代谢并形成主要活性代谢物 7-羟基-大麻二酚(7-OH-CBD),然后进一步代谢为 7-羧基-大麻二酚(7-COOH-CBD)。本研究测定了 CBD、7-OH-CBD 和 7-COOH-CBD 的血浆浓度,并评估了性别、种族和体重指数(BMI)对药代动力学变异性的潜在影响:方法: 采用先前在健康志愿者(12 人)中进行的 CBD 药物相互作用研究的血液样本。受试者口服 CBD(Epiodiolex®),每次 750 毫克,每天两次,连续服用 3 天,第 4 天服用一次。收集了 9 份血浆样本,并通过 LC-MS/MS 分析了 CBD、7-OH-CBD 和 7-COOH-CBD 的血浆浓度。计算了血浆峰值浓度(Cmax)、达到 Cmax 的时间(Tmax)、曲线下面积(AUC)和代谢物与母体药物暴露比(MPR)。对不同性别、种族、体重指数和体重的 CBD、7-OH-CBD 和 7-COOH-CBD 的 Cmax、AUC 和 MPR 的相关性进行了统计分析:CBD的平均Cmax为389.17 ± 153.23 ng/mL,平均AUC为1,542.19 ± 488.04 ng/mL*h。7-OH-CBD 的平均 Cmax 为 81.35 ± 36.64 ng/mL,平均 AUC 为 364.70 ± 105.59 ng/mL*h,平均 MPR 为 0.25 ± 0.07。7-COOH-CBD 的平均 Cmax 为 1,717.33 ± 769.22 ng/mL,平均 AUC 为 9,888.42 ± 3,961.47 ng/mL*h,平均 MPR 为 7.11 ± 3.48。就 7-COOH-CBD 而言,在体重正常化的情况下,女性受试者的 Cmax 高出 2.25 倍(p = 0.0155),AUC 高出 1.97 倍(p = 0.0285)。女性受试者的 7-OH-CBD AUC 与体重呈明显的线性关系(p = 0.0135)。Cmax、AUC 和 PMR 与种族和体重指数无明显差异:结论:观察到的性别差异与之前报道的结果一致。本研究观察到女性的 Cmax 和 AUC 较高,且女性的 Cmax 和 AUC 与体重呈显著线性关系,因此有必要进行更大规模的人群药代动力学研究,以验证这一点。
{"title":"Pharmacokinetic Variability of Oral Cannabidiol and Its Major Metabolites after Short-Term High-Dose Exposure in Healthy Subjects.","authors":"Qingchen Zhang, Philip W Melchert, John S Markowitz","doi":"10.1159/000535726","DOIUrl":"10.1159/000535726","url":null,"abstract":"<p><strong>Introduction: </strong>Cannabidiol (CBD) is a widely utilized nonpsychoactive cannabinoid available as a prescriptive drug treatment and over-the-counter supplement. In humans, CBD is metabolized and forms the major active metabolite 7-hydroxy-cannabidiol (7-OH-CBD), which is further metabolized to 7-carboxy-cannabidiol (7-COOH-CBD). In the current study, plasma concentrations of CBD, 7-OH-CBD, and 7-COOH-CBD were measured, and the potential influences of sex, race, and body mass index (BMI) on the pharmacokinetic variability were assessed.</p><p><strong>Methods: </strong>Blood samples from a previously conducted CBD drug interaction study in healthy volunteers (<i>n</i> = 12) were utilized. The subjects received orally administered CBD (Epiodiolex<sup>®</sup>), 750 mg twice daily for 3 days and a single dose on the 4th day. Nine plasma samples were collected, and plasma concentrations of CBD, 7-OH-CBD, and 7-COOH-CBD were analyzed by LC-MS/MS. Peak plasma concentration (C<sub>max</sub>), time to C<sub>max</sub> (T<sub>max</sub>), area under the curve (AUC), and metabolite-to-parent drug exposure ratios (MPR) were calculated. Statistical analysis was performed to determine the correlations of C<sub>max</sub>, AUC, and MPR of CBD, 7-OH-CBD, and 7-COOH-CBD in different sex, race, BMI, and body weight.</p><p><strong>Results: </strong>For CBD, the mean C<sub>max</sub> was 389.17 ± 153.23 ng/mL, and the mean AUC was 1,542.19 ± 488.04 ng/mL*h. For 7-OH-CBD, the mean C<sub>max</sub> was 81.35 ± 36.64 ng/mL, the mean AUC was 364.70 ± 105.59 ng/mL*h, and the mean MPR was 0.25 ± 0.07. For 7-COOH-CBD, the mean C<sub>max</sub> was 1,717.33 ± 769.22 ng/mL, the mean AUC was 9,888.42 ± 3,961.47 ng/mL*h, and the mean MPR was 7.11 ± 3.48. For 7-COOH-CBD, a 2.25-fold higher C<sub>max</sub> was observed in female subjects (<i>p</i> = 0.0155) and a 1.97-fold higher AUC for female subjects (<i>p</i> = 0.0285) with the normalization of body weight. A significant linearity (<i>p</i> = 0.0135) of 7-OH-CBD AUC with body weight in females was observed. No significant differences were identified in C<sub>max</sub>, AUC, and PMR with race and BMI.</p><p><strong>Conclusion: </strong>Observed differences in sex were in agreement with previously reported findings. A larger population pharmacokinetics study is warranted to validate the observed higher C<sub>max</sub> and AUC in females and significant linearity with body weight in females from the current study.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"7 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10824522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642524","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
Effects of Full-Spectrum Cannabis Oil with a Cannabidiol:Tetrahydrocannabinol 2:1 Ratio on the Mechanisms Involved in Hepatic Steatosis and Oxidative Stress in Rats Fed a Sucrose-Rich Diet. 大麻二酚:四氢大麻酚2:1比例的全谱大麻油对高蔗糖饮食大鼠肝脂肪变性和氧化应激机制的影响
Q1 Medicine Pub Date : 2023-11-15 eCollection Date: 2023-01-01 DOI: 10.1159/000534610
Valentina Degrave, Michelle Berenice Vega Joubert, Paola Ingaramo, Daniela Sedan, Darío Andrinolo, María Eugenia D'Alessandro, María Eugenia Oliva

Introduction: This study aimed to analyze the effects of cannabis oil (cannabidiol:tetrahydrocannabinol [CBD:THC], 2:1 ratio) on the mechanisms involved in hepatic steatosis and oxidative stress in an experimental model of metabolic syndrome (MS) induced by a sucrose-rich diet (SRD). We hypothesized that noninvasive oral cannabis oil administration improves hepatic steatosis through a lower activity of lipogenic enzymes and an increase in carnitine palmitoyltransferase-1 (CPT-1) enzyme activity involved in the mitochondrial oxidation of fatty acids. Furthermore, cannabis oil ameliorates liver oxidative stress through the regulation of the main regulatory factors involved, nuclear factor erythroid 2 (NrF2) and nuclear factor-kB (NF-κB) p65. For testing this hypothesize, a relevant experimental model of MS was induced by feeding rats with a SRD for 3 weeks.

Methods: Male Wistar rats were fed the following diets for 3 weeks: reference diet: standard commercial laboratory diet, SRD, and SRD + cannabis oil: noninvasive oral administration of 1 mg/kg body weight cannabis oil daily. The full-spectrum cannabis oil presents a total cannabinoid CBD:THC 2:1 ratio. Serum glucose, triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol, uric acid, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (AP), N-arachidonoylethanolamine or anandamide and 2-arachidonoylglycerol endocannabinoids levels, thiobarbituric acid reactive substance (TBARS) levels, and non-enzymatic antioxidant capacity (ferric ion-reducing antioxidant power [FRAP]) were evaluated. In the liver tissue: histology, nonalcoholic fatty liver disease activity score (NAS), triglycerides and cholesterol content, lipogenic enzyme activities (fatty acid synthase, acetyl-CoA carboxylase, malic enzyme, and glucose-6-phosphate dehydrogenase), enzyme related to mitochondrial fatty acid oxidation (CPT-1), reactive oxygen species, TBARS, FRAP, glutathione, catalase, glutathione peroxidase, and glutathione reductase enzyme activities. 4-hydroxynonenal, NrF2, and NF-κB p65 levels were analyzed by immunohistochemistry.

Results: The results showed that SRD-fed rats developed dyslipidemia, liver damage, hepatic steatosis (increase of key enzymes related to the novo fatty acid synthesis and decrease of key enzyme related to mitochondrial fatty acid oxidation), lipid peroxidation, and oxidative stress. Hepatic NrF2 expression was significantly decreased and NF-κB p65 expression was increased. Cannabis oil administration improved dyslipidemia, liver damage, hepatic steatosis, lipid peroxidation (improving enzymes involved in lipid metabolism), and oxidative stress. In the liver tissue, NrF2 expression increased, and NF-κB p65 expression was reduced.

Conclusion: The present study revealed new aspects of liver damage and steatosis, lipid peroxidation, and oxidative stress in dyslipidemic insulin-

摘要:本研究旨在分析大麻油(cannabidiol:tetrahydrocannabinol [CBD:THC], 2:1的比例)对富蔗糖饮食(SRD)诱导代谢综合征(MS)实验模型中肝脏脂肪变性和氧化应激机制的影响。我们假设,无创伤性口服大麻油通过降低脂肪生成酶活性和增加参与脂肪酸线粒体氧化的肉毒碱棕榈酰基转移酶-1 (CPT-1)酶活性来改善肝脂肪变性。此外,大麻油通过调节主要调控因子核因子红细胞2 (NrF2)和核因子kb (NF-κB) p65改善肝脏氧化应激。为了验证这一假设,我们用SRD喂养大鼠3周,建立了MS的相关实验模型。方法:雄性Wistar大鼠饲喂以下饮食3周:参考饮食:标准商业实验室饮食,SRD, SRD +大麻油:每天无创口服大麻油1 mg/kg体重。全谱大麻油呈现总大麻素CBD:THC 2:1的比例。评估血清葡萄糖、甘油三酯、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、尿酸、丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶(AP)、n-花生四烯酰基乙醇胺或花生酰胺和2-花生四烯酰基甘油内源性大麻素水平、硫代巴比托酸活性物质(TBARS)水平和非酶促抗氧化能力(铁离子还原抗氧化能力[FRAP])。肝组织:组织学、非酒精性脂肪肝疾病活动性评分(NAS)、甘油三酯和胆固醇含量、脂肪生成酶活性(脂肪酸合成酶、乙酰辅酶a羧化酶、苹果酸酶和葡萄糖-6-磷酸脱氢酶)、与线粒体脂肪酸氧化相关的酶(CPT-1)、活性氧、TBARS、FRAP、谷胱甘肽、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽还原酶活性。免疫组化分析4-羟基壬烯醛、NrF2、NF-κB p65水平。结果:srd喂养大鼠出现血脂异常、肝损伤、肝脂肪变性(新脂肪酸合成关键酶升高、线粒体脂肪酸氧化关键酶降低)、脂质过氧化和氧化应激。肝脏NrF2表达明显降低,NF-κB p65表达明显升高。大麻油可改善血脂异常、肝损伤、肝脂肪变性、脂质过氧化(改善参与脂质代谢的酶)和氧化应激。肝组织中NrF2表达升高,NF-κB p65表达降低。结论:本研究揭示了脂质异常胰岛素抵抗大鼠肝损伤和脂肪变性、脂质过氧化和氧化应激的新方面。在MS实验模型中,我们展示了大麻油(CBD:THC, 2:1比例)对脂肪毒性和肝脏氧化应激的新特性和分子机制。
{"title":"Effects of Full-Spectrum Cannabis Oil with a Cannabidiol:Tetrahydrocannabinol 2:1 Ratio on the Mechanisms Involved in Hepatic Steatosis and Oxidative Stress in Rats Fed a Sucrose-Rich Diet.","authors":"Valentina Degrave, Michelle Berenice Vega Joubert, Paola Ingaramo, Daniela Sedan, Darío Andrinolo, María Eugenia D'Alessandro, María Eugenia Oliva","doi":"10.1159/000534610","DOIUrl":"10.1159/000534610","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to analyze the effects of cannabis oil (cannabidiol:tetrahydrocannabinol [CBD:THC], 2:1 ratio) on the mechanisms involved in hepatic steatosis and oxidative stress in an experimental model of metabolic syndrome (MS) induced by a sucrose-rich diet (SRD). We hypothesized that noninvasive oral cannabis oil administration improves hepatic steatosis through a lower activity of lipogenic enzymes and an increase in carnitine palmitoyltransferase-1 (CPT-1) enzyme activity involved in the mitochondrial oxidation of fatty acids. Furthermore, cannabis oil ameliorates liver oxidative stress through the regulation of the main regulatory factors involved, nuclear factor erythroid 2 (NrF2) and nuclear factor-kB (NF-κB) p65. For testing this hypothesize, a relevant experimental model of MS was induced by feeding rats with a SRD for 3 weeks.</p><p><strong>Methods: </strong>Male Wistar rats were fed the following diets for 3 weeks: reference diet: standard commercial laboratory diet, SRD, and SRD + cannabis oil: noninvasive oral administration of 1 mg/kg body weight cannabis oil daily. The full-spectrum cannabis oil presents a total cannabinoid CBD:THC 2:1 ratio. Serum glucose, triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol, uric acid, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (AP), N-arachidonoylethanolamine or anandamide and 2-arachidonoylglycerol endocannabinoids levels, thiobarbituric acid reactive substance (TBARS) levels, and non-enzymatic antioxidant capacity (ferric ion-reducing antioxidant power [FRAP]) were evaluated. In the liver tissue: histology, nonalcoholic fatty liver disease activity score (NAS), triglycerides and cholesterol content, lipogenic enzyme activities (fatty acid synthase, acetyl-CoA carboxylase, malic enzyme, and glucose-6-phosphate dehydrogenase), enzyme related to mitochondrial fatty acid oxidation (CPT-1), reactive oxygen species, TBARS, FRAP, glutathione, catalase, glutathione peroxidase, and glutathione reductase enzyme activities. 4-hydroxynonenal, NrF2, and NF-κB p65 levels were analyzed by immunohistochemistry.</p><p><strong>Results: </strong>The results showed that SRD-fed rats developed dyslipidemia, liver damage, hepatic steatosis (increase of key enzymes related to the novo fatty acid synthesis and decrease of key enzyme related to mitochondrial fatty acid oxidation), lipid peroxidation, and oxidative stress. Hepatic NrF2 expression was significantly decreased and NF-κB p65 expression was increased. Cannabis oil administration improved dyslipidemia, liver damage, hepatic steatosis, lipid peroxidation (improving enzymes involved in lipid metabolism), and oxidative stress. In the liver tissue, NrF2 expression increased, and NF-κB p65 expression was reduced.</p><p><strong>Conclusion: </strong>The present study revealed new aspects of liver damage and steatosis, lipid peroxidation, and oxidative stress in dyslipidemic insulin-","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"6 1","pages":"170-183"},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138460813","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
Improved Post-Traumatic Stress Disorder Symptoms and Related Sleep Disturbances after Initiation of Medical Marijuana Use: Evidence from a Prospective Single Arm Pilot Study. 医用大麻使用后创伤后应激障碍症状和相关睡眠障碍的改善:来自前瞻性单臂先导研究的证据
Q1 Medicine Pub Date : 2023-11-13 eCollection Date: 2023-01-01 DOI: 10.1159/000534710
Krishna Vaddiparti, Yiyang Liu, Sarah Bottari, Carly Crump Boullosa, Zhi Zhou, Yan Wang, John Williamson, Robert L Cook

Introduction: Post-traumatic stress disorder (PTSD) is a debilitating disorder experienced by a subgroup of individuals following a life-threatening trauma. Several US states have passed laws permitting the medical use of marijuana (MMJ) by individuals with PTSD, despite very little scientific indication on the appropriateness of marijuana as a therapy for PTSD. This prospective pilot study of adults with confirmed PTSD in Florida (FL) investigated whether PTSD symptoms, sleep quality, affect, and general physical and mental health/well-being improved post-initiation of MMJ treatment.

Methods: Participants, N = 15, were recruited from two MMJ clinics in Gainesville and Jacksonville, FL. To be eligible, participants had to be 18 years of age or older, not currently on MMJ, and willing to abstain from recreational marijuana, if using any, until the State Medical Cannabis Card was obtained, screen positive for PTSD. Participants were assessed at baseline (pre-MMJ initiation) and 30 and 70 days post-MMJ initiation using the Pittsburgh Sleep Quality Index (PSQI), PTSD Checklist for DSM-5 (PCL-5), Positive and Negative Affect Schedule (PANAS), PROMIS Global Health V1.2, and semi-structured marijuana and other substance use assessment.

Results: PTSD symptom severity as measured by total PCL-5 score improved significantly at 30- and 70-day follow-ups. Similarly, statistically significant reductions in nightmares were reported at 30- and 70-day follow-ups. Corresponding improvements in sleep were noticed with participants reporting increased duration of sleep hours, sleep quality, sleep efficiency, and total PSQI score. Likewise, negative affect and global mental health improved significantly at follow-up. According to the post hoc analyses, the most statistically significant changes occurred between baseline and 30-day follow-up. The exception to this pattern was nightmares, which did not show significant improvement until day 70.

Conclusion: The findings of this study highlight the potential of MMJ in improving patient outcomes for those with PTSD, particularly concerning sleep disturbances, which often do not respond to currently available treatments.

简介:创伤后应激障碍(PTSD)是一种使人衰弱的障碍,是一群人在经历威胁生命的创伤后所经历的。美国几个州已经通过法律,允许PTSD患者在医疗上使用大麻(MMJ),尽管很少有科学证据表明大麻作为治疗PTSD的适当性。这项前瞻性先导研究在佛罗里达州(FL)调查PTSD症状、睡眠质量、影响和一般身心健康/幸福感是否在MMJ治疗开始后得到改善。方法:参与者,N = 15,从佛罗里达州Gainesville和Jacksonville的两家MMJ诊所招募。为了符合条件,参与者必须年满18岁,目前不使用MMJ,并且愿意放弃娱乐性大麻,如果使用任何大麻,直到获得国家医疗大麻卡,PTSD筛查阳性。参与者在基线(mmj开始前)和mmj开始后30和70天使用匹兹堡睡眠质量指数(PSQI), DSM-5 PTSD检查表(PCL-5),积极和消极影响量表(PANAS), PROMIS全球健康V1.2和半结构化大麻和其他物质使用评估进行评估。结果:在30天和70天的随访中,以总PCL-5评分衡量的PTSD症状严重程度显著改善。同样,在30天和70天的随访中,噩梦的数量也有统计学上的显著减少。随着参与者报告睡眠时间、睡眠质量、睡眠效率和PSQI总分的增加,睡眠得到了相应的改善。同样,在随访中,消极情绪和整体心理健康也有显著改善。根据事后分析,最具统计学意义的变化发生在基线和30天随访期间。这种模式的例外是噩梦,直到第70天才显示出显著的改善。结论:这项研究的发现强调了MMJ在改善PTSD患者预后方面的潜力,特别是在睡眠障碍方面,目前可用的治疗方法通常对睡眠障碍没有反应。
{"title":"Improved Post-Traumatic Stress Disorder Symptoms and Related Sleep Disturbances after Initiation of Medical Marijuana Use: Evidence from a Prospective Single Arm Pilot Study.","authors":"Krishna Vaddiparti, Yiyang Liu, Sarah Bottari, Carly Crump Boullosa, Zhi Zhou, Yan Wang, John Williamson, Robert L Cook","doi":"10.1159/000534710","DOIUrl":"10.1159/000534710","url":null,"abstract":"<p><strong>Introduction: </strong>Post-traumatic stress disorder (PTSD) is a debilitating disorder experienced by a subgroup of individuals following a life-threatening trauma. Several US states have passed laws permitting the medical use of marijuana (MMJ) by individuals with PTSD, despite very little scientific indication on the appropriateness of marijuana as a therapy for PTSD. This prospective pilot study of adults with confirmed PTSD in Florida (FL) investigated whether PTSD symptoms, sleep quality, affect, and general physical and mental health/well-being improved post-initiation of MMJ treatment.</p><p><strong>Methods: </strong>Participants, <i>N</i> = 15, were recruited from two MMJ clinics in Gainesville and Jacksonville, FL. To be eligible, participants had to be 18 years of age or older, not currently on MMJ, and willing to abstain from recreational marijuana, if using any, until the State Medical Cannabis Card was obtained, screen positive for PTSD. Participants were assessed at baseline (pre-MMJ initiation) and 30 and 70 days post-MMJ initiation using the Pittsburgh Sleep Quality Index (PSQI), PTSD Checklist for DSM-5 (PCL-5), Positive and Negative Affect Schedule (PANAS), PROMIS Global Health V1.2, and semi-structured marijuana and other substance use assessment.</p><p><strong>Results: </strong>PTSD symptom severity as measured by total PCL-5 score improved significantly at 30- and 70-day follow-ups. Similarly, statistically significant reductions in nightmares were reported at 30- and 70-day follow-ups. Corresponding improvements in sleep were noticed with participants reporting increased duration of sleep hours, sleep quality, sleep efficiency, and total PSQI score. Likewise, negative affect and global mental health improved significantly at follow-up. According to the post hoc analyses, the most statistically significant changes occurred between baseline and 30-day follow-up. The exception to this pattern was nightmares, which did not show significant improvement until day 70.</p><p><strong>Conclusion: </strong>The findings of this study highlight the potential of MMJ in improving patient outcomes for those with PTSD, particularly concerning sleep disturbances, which often do not respond to currently available treatments.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"6 1","pages":"160-169"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10642978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107591653","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
Absorption and Bioavailability of Novel UltraShear Nanoemulsion of Cannabidiol in Rats. 新型大麻二酚超剪切纳米乳液在大鼠体内的吸收和生物利用度。
Q1 Medicine Pub Date : 2023-11-07 eCollection Date: 2023-01-01 DOI: 10.1159/000534473
Mahmoud A ElSohly, Iram Shahzadi, Waseem Gul

Introduction: Cannabidiol (CBD) has several potential benefits and therapeutic uses, especially in pain, inflammation, and anxiety. CBD has high hydrophobicity and very low solubility in water. CBD has also shown exceptionally low oral-gastrointestinal (oral-GI) bioavailability. In this study, we aimed to examine the oral gastrointestinal absorption and subsequent bioavailability of CBD in a nanoemulsion formulation prepared by Pressure BioSciences' UltraShearTM technology.

Methods: CBD nanoemulsion (2%) was provided by Pressure BioSciences, Inc. (South Easton, MA), and CBD pharmacokinetic parameters were evaluated in male Sprague-Dawley rats using LC-MS/MS technology.

Results: Bioavailability of orally delivered CBD UltraShear nanoemulsion was calculated to be 18.6% at 6 h and 25.4% at 24 h. While oral-GI bioavailability is unsurprisingly limited by first-pass metabolism, it is nonetheless notable that CBD bioavailability for oral-GI UltraShear nanoemulsion CBD is roughly 3-4x higher than the typical bioavailability for oral-GI CBD delivered in oil solution or conventional edible formats.

Conclusion: This study has provided a compelling demonstration of unprecedented speed and efficiency of oral-GI CBD absorption of CBD UltraShear nanoemulsions, achieving 10% of levels achieved for direct IV injection within 30 min and 80% of IV levels in 24 h. Notably, within just the first hour post-administration, the bioavailability of oral CBD from UltraShear nanoemulsion formulation exceeded the typical 6% total CBD oral bioavailability benchmarks reported for CBD edibles and ultimately achieved 3-4X these levels within 6-24 h.

简介:大麻二酚(CBD)具有多种潜在的益处和治疗用途,尤其是在疼痛、炎症和焦虑方面。CBD具有高疏水性和在水中的极低溶解度。CBD还显示出异常低的口服胃肠道(口服GI)生物利用度。在本研究中,我们旨在检测通过Pressure BioSciences的UltraShearTM技术制备的纳米乳液制剂中CBD的口服胃肠道吸收和随后的生物利用度。方法:由Pressure BioSciences,股份有限公司(South Easton,MA)提供CBD纳米乳液(2%),并使用LC-MS/MS技术评估雄性Sprague-Dawley大鼠的CBD药代动力学参数。结果:经计算,口服递送的CBD UltraShear纳米乳液的生物利用度在6小时时为18.6%,在24小时时为25.4%。虽然口服胃肠道生物利用度受到首过代谢的限制并不奇怪,然而值得注意的是,口服GI UltraShear纳米乳液CBD的CBD生物利用度比以油溶液或传统可食用形式递送的口服GI CBD的典型生物利用度高大约3-4倍。结论:这项研究有力地证明了CBD UltraShear纳米乳液口服胃肠道CBD吸收的速度和效率是前所未有的,在30分钟内达到了直接静脉注射的10%,在24小时内达到了静脉注射的80%。值得注意的是,在给药后的第一个小时内,UltraShear纳米乳液制剂的口服CBD的生物利用度超过了CBD食品报道的典型的6%的总CBD口服生物利用度基准,并最终在6-24小时内达到了这些水平的3-4X。
{"title":"Absorption and Bioavailability of Novel UltraShear Nanoemulsion of Cannabidiol in Rats.","authors":"Mahmoud A ElSohly, Iram Shahzadi, Waseem Gul","doi":"10.1159/000534473","DOIUrl":"10.1159/000534473","url":null,"abstract":"<p><strong>Introduction: </strong>Cannabidiol (CBD) has several potential benefits and therapeutic uses, especially in pain, inflammation, and anxiety. CBD has high hydrophobicity and very low solubility in water. CBD has also shown exceptionally low oral-gastrointestinal (oral-GI) bioavailability. In this study, we aimed to examine the oral gastrointestinal absorption and subsequent bioavailability of CBD in a nanoemulsion formulation prepared by Pressure BioSciences' UltraShear<sup>TM</sup> technology.</p><p><strong>Methods: </strong>CBD nanoemulsion (2%) was provided by Pressure BioSciences, Inc. (South Easton, MA), and CBD pharmacokinetic parameters were evaluated in male Sprague-Dawley rats using LC-MS/MS technology.</p><p><strong>Results: </strong>Bioavailability of orally delivered CBD UltraShear nanoemulsion was calculated to be 18.6% at 6 h and 25.4% at 24 h. While oral-GI bioavailability is unsurprisingly limited by first-pass metabolism, it is nonetheless notable that CBD bioavailability for oral-GI UltraShear nanoemulsion CBD is roughly 3-4x higher than the typical bioavailability for oral-GI CBD delivered in oil solution or conventional edible formats.</p><p><strong>Conclusion: </strong>This study has provided a compelling demonstration of unprecedented speed and efficiency of oral-GI CBD absorption of CBD UltraShear nanoemulsions, achieving 10% of levels achieved for direct IV injection within 30 min and 80% of IV levels in 24 h. Notably, within just the first hour post-administration, the bioavailability of oral CBD from UltraShear nanoemulsion formulation exceeded the typical 6% total CBD oral bioavailability benchmarks reported for CBD edibles and ultimately achieved 3-4X these levels within 6-24 h.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"6 1","pages":"148-159"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71522049","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
期刊
Medical Cannabis and Cannabinoids
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1