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Pharmacological Characterization of the Endocannabinoid Sensor GRABeCB2.0. 内源性大麻素传感器 GRABeCB2.0 的药理学特征。
IF 3.1 4区 医学
Cannabis and Cannabinoid Research Pub Date : 2024-10-01 Epub Date: 2023-12-08 DOI: 10.1089/can.2023.0036
Simar Singh, Dennis Sarroza, Anthony English, Maya McGrory, Ao Dong, Larry Zweifel, Benjamin B Land, Yulong Li, Michael R Bruchas, Nephi Stella
{"title":"Pharmacological Characterization of the Endocannabinoid Sensor GRAB<sub>eCB2.0</sub>.","authors":"Simar Singh, Dennis Sarroza, Anthony English, Maya McGrory, Ao Dong, Larry Zweifel, Benjamin B Land, Yulong Li, Michael R Bruchas, Nephi Stella","doi":"10.1089/can.2023.0036","DOIUrl":"10.1089/can.2023.0036","url":null,"abstract":"<p><p><b>Introduction:</b> The endocannabinoids (eCBs), 2-arachidonoylglycerol (2-AG) and arachidonoyl ethanolamine (AEA), are produced by separate enzymatic pathways, activate cannabinoid (CB) receptors with distinct pharmacological profiles, and differentially regulate pathophysiological processes. The genetically encoded sensor, GRAB<sub>eCB2.0</sub>, detects real-time changes in eCB levels in cells in culture and preclinical model systems; however, its activation by eCB analogues produced by cells and by phyto-CBs remains uncharacterized, a current limitation when interpreting changes in its response. This information could provide additional utility for the tool in <i>in vivo</i> pharmacology studies of phyto-CB action. <b>Materials and Methods:</b> GRAB<sub>eCB2.0</sub> was expressed in cultured HEK293 cells. Live cell confocal microscopy and high-throughput fluorescent signal measurements. <b>Results:</b> 2-AG increased GRAB<sub>eCB2.0</sub> fluorescent signal (EC<sub>50</sub>=85 nM), and the cannabinoid 1 receptor (CB<sub>1</sub>R) antagonist, SR141716 (SR1), decreased GRAB<sub>eCB2.0</sub> signal (IC<sub>50</sub>=3.3 nM), responses that mirror their known potencies at the CB<sub>1</sub>R. GRAB<sub>eCB2.0</sub> fluorescent signal also increased in response to AEA (EC<sub>50</sub>=815 nM), the eCB analogues 2-linoleoylglycerol and 2-oleoylglycerol (EC<sub>50</sub>=632 and 868 nM, respectively), Δ<sup>9</sup>-tetrahydrocannabinol (Δ<sup>9</sup>-THC), and Δ<sup>8</sup>-THC (EC<sub>50</sub>=1.6 and 2.0 μM, respectively), and the artificial CB<sub>1</sub>R agonist, CP55,940 (CP; EC<sub>50</sub>=82 nM); however their potencies were less than what has been described at CB<sub>1</sub>R. Cannabidiol (CBD) did not affect basal GRAB<sub>eCB2.0</sub> fluorescent signal and yet reduced the 2-AG stimulated GRAB<sub>eCB2.0</sub> responses (IC<sub>50</sub>=9.7 nM). <b>Conclusions:</b> 2-AG and SR1 modulate the GRAB<sub>eCB2.0</sub> fluorescent signal with EC<sub>50</sub> values that mirror their potencies at CB<sub>1</sub>R, whereas AEA, eCB analogues, THC, and CP increase GRAB<sub>eCB2.0</sub> fluorescent signal with EC<sub>50</sub> values significantly lower than their potencies at CB<sub>1</sub>R. CBD reduces the 2-AG response without affecting basal signal, suggesting that GRAB<sub>eCB2.0</sub> retains the negative allosteric modulator (NAM) property of CBD at CB<sub>1</sub>R. This study describes the pharmacological profile of GRAB<sub>eCB2.0</sub> to improve interpretation of changes in fluorescent signal in response to a series of known eCBs and CB<sub>1</sub>R ligands.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"1250-1266"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138797156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Understanding Cannabis-Related Information Needs: An Analysis of Inquiries to the National Cancer Institute's Cancer Information Service. 了解大麻相关的信息需求:对美国癌症研究所癌症信息服务的调查分析。
IF 3.1 4区 医学
Cannabis and Cannabinoid Research Pub Date : 2024-10-01 Epub Date: 2023-10-19 DOI: 10.1089/can.2023.0119
George Kueppers, Grace Huang, David Dean, Joseph T Ciccolo, Robin C Vanderpool
{"title":"Understanding Cannabis-Related Information Needs: An Analysis of Inquiries to the National Cancer Institute's Cancer Information Service.","authors":"George Kueppers, Grace Huang, David Dean, Joseph T Ciccolo, Robin C Vanderpool","doi":"10.1089/can.2023.0119","DOIUrl":"10.1089/can.2023.0119","url":null,"abstract":"<p><p><b>Purpose:</b> Given increased cannabis use for medical and nonmedical purposes alike, there is growing public interest related to the potential risks and benefits of cannabis use, particularly related to cancer. The purpose of this descriptive study was to analyze cannabis inquiries to the National Cancer Institute's Cancer Information Service (CIS). <b>Materials and Methods:</b> From September 2018 to June 2023, 190,070 noncannabis and 425 cannabis inquiries were documented by the CIS. Cannabis inquiries were delineated into two categories: nonmedical cannabis (NMC, <i>n</i>=240) or medical cannabis (MC, <i>n</i>=185). Chi-square tests were performed to determine differences between noncannabis and cannabis inquiries and descriptive analyses were used to identify patterns within cannabis-specific inquiries. <b>Results:</b> Statistically significant differences between noncannabis and cannabis inquiries were observed. In addition, there were variations in MC and NMC inquiries. For example, 73% of MC inquiries originated from cancer survivors and caregivers, whereas almost half of NMC inquiries (48%) were from individuals identifying as tobacco users. MC and NMC inquiries also differed by CIS access channel (e.g., instant chat, telephone), language used (English vs. Spanish), discussions of cancer continuum phases and cancer sites, and referrals provided to individuals for additional information and resources. <b>Conclusion:</b> Cannabis-related information needs of the public-as documented by the CIS-varied by several factors. Health information sources such as the CIS can help address cannabis-related questions and concerns, while noting differences in who is inquiring, how, and why.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e1452-e1458"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49674613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Electrophysiological Phenotypes of Hippocampal Synaptic and Network Functions in Cannabinoid Receptor 2 Knockout Mice. 大麻素受体 2 基因敲除小鼠海马突触和网络功能的电生理学表型
IF 3.1 4区 医学
Cannabis and Cannabinoid Research Pub Date : 2024-10-01 Epub Date: 2024-01-22 DOI: 10.1089/can.2023.0186
Shuangtao Li, Yongchang He, Dharshaun Turner, Naili Wei, Luyao Ma, Devin H Taylor, Danielle T Taylor, Xiaoyu Ji, Jie Wu
{"title":"Electrophysiological Phenotypes of Hippocampal Synaptic and Network Functions in Cannabinoid Receptor 2 Knockout Mice.","authors":"Shuangtao Li, Yongchang He, Dharshaun Turner, Naili Wei, Luyao Ma, Devin H Taylor, Danielle T Taylor, Xiaoyu Ji, Jie Wu","doi":"10.1089/can.2023.0186","DOIUrl":"10.1089/can.2023.0186","url":null,"abstract":"<p><p><b>Background:</b> The cannabinoid receptor 2 (CB2R), a cannabinoid receptor primarily expressed in immune cells, has been found in the brain, particularly in the hippocampus, where it plays crucial roles in modulating various neural functions, including synaptic plasticity, neuroprotection, neurogenesis, anxiety and stress responses, and neuroinflammation. Despite this growing understanding, the intricate electrophysiological characteristics of hippocampal neurons in CB2R knockout (CB2R KO) mice remain elusive. <b>Aim and Methods:</b> This study aimed to comprehensively assess the electrophysiological traits of hippocampal synaptic and network functions in CB2R KO mice. The focus was on aspects such as synaptic transmission, short- and long-term synaptic plasticity, and neural network synchrony (theta oscillations). <b>Results:</b> Our findings unveiled multiple functional traits in these CB2R KO mice, notably elevated synaptic transmission in hippocampal CA1 neurons, decreased both synaptic short-term plasticity (paired-pulse facilitation) and long-term potentiation (LTP), and impaired neural network synchronization. <b>Conclusion:</b> In essence, this study yields insightful revelations about the influence of CB2Rs on hippocampal neural functions. By illuminating the electrophysiological modifications in CB2R KO mice, our research enriches the comprehension of CB2R involvement in hippocampal function. Such insights could hold implications for advancing our understanding of the neural mechanisms under the influence of CB2Rs within the brain.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"1267-1276"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140173780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Repeated Administration of a Full-Spectrum Cannabidiol Product, Not a Cannabidiol Isolate, Reverses the Lipopolysaccharide-Induced Depressive-Like Behavior and Hypolocomotion in a Rat Model of Low-Grade Subchronic Inflammation. 在低度亚慢性炎症大鼠模型中,重复给药全谱大麻二酚产品(而非大麻二酚异构体)可逆转脂多糖诱发的抑郁样行为和运动过少。
IF 3.1 4区 医学
Cannabis and Cannabinoid Research Pub Date : 2024-09-30 DOI: 10.1089/can.2024.0086
Linério Ribeiro de Novais Júnior, Tiago Vicente da Silva, Larissa Mendes da Silva, Flavia Metzker de Andrade, Alisson Reuel da Silva, Vicente Meneguzzo, Suelen de Souza Ramos, Cyntia Michielin Lopes, Artur Bernardo Saturnino, Antonio Inserra, Rafael Mariano de Bitencourt
{"title":"Repeated Administration of a Full-Spectrum Cannabidiol Product, Not a Cannabidiol Isolate, Reverses the Lipopolysaccharide-Induced Depressive-Like Behavior and Hypolocomotion in a Rat Model of Low-Grade Subchronic Inflammation.","authors":"Linério Ribeiro de Novais Júnior, Tiago Vicente da Silva, Larissa Mendes da Silva, Flavia Metzker de Andrade, Alisson Reuel da Silva, Vicente Meneguzzo, Suelen de Souza Ramos, Cyntia Michielin Lopes, Artur Bernardo Saturnino, Antonio Inserra, Rafael Mariano de Bitencourt","doi":"10.1089/can.2024.0086","DOIUrl":"https://doi.org/10.1089/can.2024.0086","url":null,"abstract":"<p><p><b>Background:</b> Mounting evidence suggests that the phytocannabinoid cannabidiol (CBD) holds promise as an antidepressant agent in conditions underlined by inflammation. Full-spectrum CBD extracts might provide greater behavioral efficacy than CBD-only isolates and might require lower doses to achieve the same outcomes due to the presence of other cannabinoids, terpenes, and flavonoids. However, investigations in this area remain limited. <b>Methods:</b> We evaluated the behavioral response to the administration for 7 days of 15 and 30 mg/kg of a CBD isolate and a full-spectrum CBD product in a rat model of subchronic lipopolysaccharide (LPS, 0.5 mg/kg/day/7 days, intraperitoneal)-induced depressive-like and sickness behavior. The forced swim test was used to assess depressive-like behavior, the open field test (OFT) to assess locomotion, and the elevated plus maze to assess anxiety-like behavior. <b>Results:</b> The full-spectrum CBD extract at both doses, but not the CBD isolate, reversed the LPS-induced depressive-like behavior in the forced swim test. Moreover, the full-spectrum CBD extract at the higher dose but not the CBD isolate restored the subchronic LPS-induced hypolocomotion in the OFT. Repeated administration of both formulations elicited an anxiogenic-like trend in the elevated plus maze. <b>Conclusion:</b> Full-spectrum CBD products might have greater therapeutic efficacy in resolving inflammation-induced depressive and sickness behavior compared to a CBD-only isolate.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of Cannabistilbene I in Attenuating Angiotensin II-Induced Cardiac Hypertrophy: Insights into Cytochrome P450s and Arachidonic Acid Metabolites Modulation. 大麻芪 I 在减轻血管紧张素 II 诱导的心肌肥大中的作用:洞察细胞色素 P450s 和花生四烯酸代谢物的调节作用。
IF 3.1 4区 医学
Cannabis and Cannabinoid Research Pub Date : 2024-09-26 DOI: 10.1089/can.2024.0148
Ahmad H Alammari, Fadumo Ahmed Isse, Conor O'Croinin, Neal M Davies, Ayman O S El-Kadi
{"title":"Effect of Cannabistilbene I in Attenuating Angiotensin II-Induced Cardiac Hypertrophy: Insights into Cytochrome P450s and Arachidonic Acid Metabolites Modulation.","authors":"Ahmad H Alammari, Fadumo Ahmed Isse, Conor O'Croinin, Neal M Davies, Ayman O S El-Kadi","doi":"10.1089/can.2024.0148","DOIUrl":"https://doi.org/10.1089/can.2024.0148","url":null,"abstract":"<p><p><b>Introduction:</b> This research investigated the impact of Cannabistilbene I on Angiotensin II (Ang II)-induced cardiac hypertrophy and its potential role in cytochrome P450 (CYP) enzymes and arachidonic acid (AA) metabolic pathways. Cardiac hypertrophy, a response to increased stress on the heart, can lead to severe cardiovascular diseases if not managed effectively. CYP enzymes and AA metabolites play critical roles in cardiac function and hypertrophy, making them important targets for therapeutic intervention. <b>Methods:</b> Adult human ventricular cardiomyocyte cell line (AC16) was cultured and treated with Cannabistilbene I in the presence and absence of Ang II. The effects on mRNA expression related to cardiac hypertrophic markers and CYP were analyzed using real-time polymerase chain reaction, while CYP protein levels were measured by Western blot analysis. AA metabolites were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). <b>Results:</b> Results showed that Ang II triggered hypertrophy, as evidenced by the increase in hypertrophic marker expression, and enlarged the cell surface area, effects that were alleviated by Cannabistilbene I. Gene expression analysis indicated that Cannabistilbene I upregulated CYP1A1, leading to increased enzymatic activity, as evidenced by 7-ethoxyresorufin-O-deethylase assay. Furthermore, LC-MS/MS analysis of AA metabolites revealed that Ang II elevated midchain (R/S)-hydroxyeicosatetraenoic acid (HETE) concentrations, which were reduced by Cannabistilbene I. Notably, Cannabistilbene I selectively increased 19(S)-HETE concentration and reversed the Ang II-induced decline in 19(S)-HETE, suggesting a unique protective role. <b>Conclusion:</b> This study provides new insights into the potential of Cannabistilbene I in modulating AA metabolites and reducing Ang II-induced cardiac hypertrophy, revealing a new candidate as a therapeutic agent for cardiac hypertrophy.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Statewide Examination of Medical Cannabis Purchasing Patterns in Arkansas Over the Three Years Immediately Following Legalization. 对阿肯色州在大麻合法化后三年内医用大麻购买模式的全州范围调查。
IF 3.1 4区 医学
Cannabis and Cannabinoid Research Pub Date : 2024-09-23 DOI: 10.1089/can.2024.0141
Bradley C Martin, Joseph W Thompson, Anthony Goudie, Cain Farnam, Katerina Noori, Nichole Stanley, Jaclyn R Daniels, Teresa J Hudson
{"title":"A Statewide Examination of Medical Cannabis Purchasing Patterns in Arkansas Over the Three Years Immediately Following Legalization.","authors":"Bradley C Martin, Joseph W Thompson, Anthony Goudie, Cain Farnam, Katerina Noori, Nichole Stanley, Jaclyn R Daniels, Teresa J Hudson","doi":"10.1089/can.2024.0141","DOIUrl":"10.1089/can.2024.0141","url":null,"abstract":"<p><p><b>Introduction:</b> The use of medical cannabis (MC) to treat a host of conditions has expanded considerably in the United States; however, precise quantitative assessments of purchasing characteristics are unknown. This study sought to characterize the trends in MC purchases, US dollars spent, and type and amount purchased by demographic and clinical characteristics. <b>Materials and Methods:</b> This descriptive exploratory association study examined statewide MC registry data in Arkansas linked at the person level with statewide transaction data documenting each MC purchase. MC transaction data (May 11, 2019-August 31, 2022) were assessed to identify persons who could be linked to the registry data and made at least one purchase. Individual demographic characteristics and MC qualifying conditions (QCs) were ascertained. Product types were classified into plant cannabis, cannabis extract for inhalation (vape), edibles, and others. The average daily total delta-9-tetrahydrocannabinol (THC) purchased was calculated based on the concentration and quantity purchased. Purchasing characteristics are described and demographic and clinical factors associated with THC purchased per day and dollars spent per year were estimated by ordinary least square regression and general linear models with a gamma distribution. <b>Results:</b> On average, 89,057 MC purchasers spent $3343 (interquartile range [IQR], $907-$4802), had 33.34 (IQR, 8.32-46.03) transaction days per year, and purchased 162.32 mg (IQR, 30.51-237.69) of THC per day. Most persons predominantly purchased plant cannabis (68.27%), followed by edibles (14.92%) and vape (11.96%). Individuals younger than 18 years of age (β=-78.23; 95% confidence interval [CI], -116.599 to -39.863), persons 70 and older (β = -122.30; 95% CI, -128.18 to -116.422), and women (β=-33.70; 95% CI, -35.95 to -31.446) purchased less THC per day than their counterparts after multivariate adjustment. The most common QCs were pain and post-traumatic stress disorder (PTSD), and compared to those with cancer, persons with pain (β = 26.30; 95% CI, 18.636-33.96) and PTSD (β = 38.34; 95% CI, 30.467-46.222) purchased more THC per day. <b>Conclusion:</b> The average THC purchased per person per day exceeds typically recommended daily doses for therapeutic uses, and further research is warranted to assess the safety and benefits of MC across these conditions.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association of Serum Endocannabinoid Levels with Pancreatitis and Pancreatitis-Related Pain. 血清内源性大麻素水平与胰腺炎及胰腺炎相关疼痛的关系
IF 3.1 4区 医学
Cannabis and Cannabinoid Research Pub Date : 2024-09-18 DOI: 10.1089/can.2024.0079
Marc T Goodman, Christina Lombardi, Alexa Torrens, Catherine Bresee, Jami L Saloman, Liang Li, Yunlong Yang, William E Fisher, Evan L Fogel, Christopher E Forsmark, Darwin L Conwell, Phil A Hart, Walter G Park, Mark Topazian, Santhi S Vege, Stephen K Van Den Eeden, Melena D Bellin, Dana K Andersen, Jose Serrano, Dhiraj Yadav, Stephen J Pandol, Daniele Piomelli
{"title":"Association of Serum Endocannabinoid Levels with Pancreatitis and Pancreatitis-Related Pain.","authors":"Marc T Goodman, Christina Lombardi, Alexa Torrens, Catherine Bresee, Jami L Saloman, Liang Li, Yunlong Yang, William E Fisher, Evan L Fogel, Christopher E Forsmark, Darwin L Conwell, Phil A Hart, Walter G Park, Mark Topazian, Santhi S Vege, Stephen K Van Den Eeden, Melena D Bellin, Dana K Andersen, Jose Serrano, Dhiraj Yadav, Stephen J Pandol, Daniele Piomelli","doi":"10.1089/can.2024.0079","DOIUrl":"https://doi.org/10.1089/can.2024.0079","url":null,"abstract":"<p><p><b>Background and Aims:</b> This investigation examined the association of pancreatitis and pancreatitis-related pain with serum levels of two endocannabinoid molecules such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and two paracannabinoid molecules such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). <b>Methods:</b> A case-control study was conducted within the Prospective Evaluation of Chronic Pancreatitis for Epidemiological and Translational Studies, including participants with no pancreas disease (<i>N</i> = 56), chronic abdominal pain of suspected pancreatic origin or indeterminate chronic pancreatitis (CP) (<i>N</i> = 22), acute pancreatitis (<i>N</i> = 33), recurrent acute pancreatitis (<i>N</i> = 57), and definite CP (<i>N</i> = 63). <b>Results:</b> Circulating AEA concentrations were higher in women than in men (<i>p</i> = 0.0499), and PEA concentrations were higher in obese participants than those who were underweight/normal or overweight (<i>p</i> = 0.003). Asymptomatic controls with no pancreatic disease had significantly (<i>p</i> = 0.03) lower concentrations of AEA compared with all disease groups combined. The highest concentrations of AEA were observed in participants with acute pancreatitis, followed by those with recurrent acute pancreatitis, chronic abdominal pain/indeterminant CP, and definite CP. Participants with pancreatitis reporting abdominal pain in the past year had significantly (<i>p</i> = 0.04) higher concentrations of AEA compared with asymptomatic controls. Levels of 2-AG were significantly lower (<i>p</i> = 0.02) among participants reporting abdominal pain in the past week, and pain intensity was inversely associated with concentrations of 2-AG and OEA. <b>Conclusions:</b> Endocannabinoid levels may be associated with stage of pancreatitis, perhaps through activation of the CB1 receptor. Validation of our findings would support the investigation of novel therapeutics, including cannabinoid receptor-1 antagonists, in this patient population.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Endometrial Cell-Type Specific Regulation of the Endocannabinoids System and the Impact of Menstrual Cycle and Endometriosis. 子宫内膜细胞类型对内源性大麻素系统的特定调节以及月经周期和子宫内膜异位症的影响。
IF 3.1 4区 医学
Cannabis and Cannabinoid Research Pub Date : 2024-09-17 DOI: 10.1089/can.2024.0081
Keisuke Tanaka, Sugarniya Subramaniam, Sharat Atluri, Akwasi A Amoako, Sally Mortlock, Grant W Montgomery, Brett McKinnon
{"title":"Endometrial Cell-Type Specific Regulation of the Endocannabinoids System and the Impact of Menstrual Cycle and Endometriosis.","authors":"Keisuke Tanaka, Sugarniya Subramaniam, Sharat Atluri, Akwasi A Amoako, Sally Mortlock, Grant W Montgomery, Brett McKinnon","doi":"10.1089/can.2024.0081","DOIUrl":"https://doi.org/10.1089/can.2024.0081","url":null,"abstract":"<p><p><b>Introduction:</b> Anandamide (AEA) and 2-arachidonoylglycerol are endogenous agonists of the cannabinoid receptors and regulate and control many cellular functions. Their activities are governed by enzymes and proteins that regulate their synthesis, receptor binding, transport, and degradation, which are known as the endocannabinoid system (ECS). The aim of this study was to investigate the regulation of endocannabinoid activity in the endometrium by studying the RNA and protein expression of the ECS within endometrial cell types and during different menstrual cycle stages and the impact of endometriosis. <b>Materials and Methods:</b> The RNA expression of 70 ECS genes was assessed using RNA sequencing of isolated endometrial epithelial and stromal cells. Subsequent immunofluorescence-stained endometrial samples on ECS components of interest were objectively analyzed <i>via</i> an agnostic and automated image analysis pipeline to extract quantitative information. Differential gene and protein expression was investigated between the two cell types, menstrual cycle phases, and endometriosis cases and controls. <b>Results:</b> Sufficient RNA expression was detected for 45 genes, and 17 (38%) genes were significantly different between epithelial and stromal cells. <i>FAAH</i> RNA was significantly higher in epithelial cells compared with stromal cells. Protein expression analysis of the main synthesizing (NAPE-PLD) and catabolizing (FAAH and NAAA) enzymes of AEA revealed a significantly stronger epithelial expression compared to stromal cells. The RNA and protein expression of CB1 receptors was very low with no significant difference between epithelial and stromal cells. Eleven ECS genes were regulated across the menstrual cycle, and there was no gene with significant difference between endometriosis cases and controls in epithelial cells. <b>Discussion:</b> Differential expression of ECS genes supports a cell type-specific endocannabinoid activity in the endometrium. As endocannabinoids are short-lived signaling molecules, higher RNA and protein expression of FAAH in the epithelial cells suggests an active regulation of endocannabinoid activity in epithelial cells within the endometrium.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Associations of Cannabis Use, Metabolic Dysfunction-Associated Steatotic Liver Disease, and Liver Fibrosis in U.S. Adults. 美国成年人吸食大麻、代谢功能障碍相关性脂肪性肝病和肝纤维化的相关性。
IF 3.1 4区 医学
Cannabis and Cannabinoid Research Pub Date : 2024-09-17 DOI: 10.1089/can.2024.0027
Yu Wu, Fei Fang, Xingliang Fan, Hongming Nie
{"title":"Associations of Cannabis Use, Metabolic Dysfunction-Associated Steatotic Liver Disease, and Liver Fibrosis in U.S. Adults.","authors":"Yu Wu, Fei Fang, Xingliang Fan, Hongming Nie","doi":"10.1089/can.2024.0027","DOIUrl":"https://doi.org/10.1089/can.2024.0027","url":null,"abstract":"<p><p><b>Introduction:</b> Following the introduction of metabolic dysfunction-associated steatotic liver disease (MASLD) as a replacement term for nonalcoholic fatty liver disease, the relationship between MASLD and cannabis use has yet to be established. With the global rise in cannabis consumption, understanding its impact on MASLD is critical for clinical guidance. Our study investigated the association between cannabis use, MASLD, and clinically significant fibrosis (CSF) among U.S. adults. <b>Methods:</b> Data were collected from the National Health and Nutrition Examination Survey for the period 2017 to 2018 to conduct a cross-sectional analysis. The diagnosis of hepatic steatosis and CSF was based on median values of the controlled attenuation parameter and liver stiffness measurement, with thresholds of 285 dB/m and 8.6 kPa, respectively. Information on cannabis use was obtained through self-report questionnaires. Multinomial logistic regression models and subgroup analyses were used to investigate the association between cannabis use and MASLD with CSF. <b>Results:</b> Our study assessed data from 2,756 U.S. adults (51.1% female; 32.2% white; mean age 39.41 ± 11.83 years), who had complete information on liver stiffness measurements through transient elastography alongside reported cannabis use. Results indicated that cannabis use overall was not associated with liver stiffness in patients with MASLD. However, among females, cannabis use was associated with MASLD accompanied by CSF, with an adjusted odds ratio (OR) of 0.47 (95% confidence interval [CI]: 0.24-0.91). Heavy cannabis use (9 to 30 times per month) was associated with MASLD accompanied by CSF among female participants, with an adjusted OR of 0.12 (95% CI: 0.02-0.88). <b>Conclusion:</b> In our study, cannabis use did not show a significant association with liver stiffness in patients diagnosed with MASLD. However, heavy cannabis consumption in women was associated with MASLD accompanied by CSF. These findings suggest that the effects of cannabis on liver health may differ based on gender and frequency of cannabis use, emphasizing the need for further research in this area.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neonatal Cannabidiol Exposure Impairs Spatial Memory and Disrupts Neuronal Dendritic Morphology in Young Adult Rats. 新生儿大麻二酚暴露会损害年轻成年大鼠的空间记忆并破坏其神经元树突形态学
IF 3.1 4区 医学
Cannabis and Cannabinoid Research Pub Date : 2024-09-10 DOI: 10.1089/can.2024.0010
Meetu Wadhwa, Gregory A Chinn, Jennifer M Sasaki Russell, Judith Hellman, Jeffrey W Sall
{"title":"Neonatal Cannabidiol Exposure Impairs Spatial Memory and Disrupts Neuronal Dendritic Morphology in Young Adult Rats.","authors":"Meetu Wadhwa, Gregory A Chinn, Jennifer M Sasaki Russell, Judith Hellman, Jeffrey W Sall","doi":"10.1089/can.2024.0010","DOIUrl":"https://doi.org/10.1089/can.2024.0010","url":null,"abstract":"<p><p><b>Introduction:</b> Early life is a sensitive period for brain development. Perinatal exposure to cannabis is increasingly linked to disruption of neurodevelopment; however, research on the effects of cannabidiol (CBD) on the developing brain is scarce. In this study, we aim to study the developmental effects of neonatal CBD exposure on behavior and dendritic architecture in young adult rats. <b>Materials and Methods:</b> Male and female neonatal Sprague Dawley rats were treated with CBD (50 mg/kg) intraperitoneally on postnatal day (PND) 1, 3, and 5 and evaluated for behavioral and neuronal morphological changes during early adulthood. Rats were subjected to a series of behavioral tasks to evaluate long-term effects of neonatal CBD exposure, including the Barnes maze, open field, and elevated plus maze paradigms to assess spatial memory and anxiety-like behavior. Following behavioral evaluation, animals were sacrificed, and neuronal morphology of the cortex and hippocampus was assessed using Golgi-Cox (GC) staining. <b>Results:</b> Rats treated with CBD displayed a sexually dimorphic response in spatial memory, with CBD-treated females developing a deficit but not males. CBD did not elicit alterations in anxiety-like behavior in either sex. Neonatal CBD caused an overall decrease in dendritic length and spine density (apical and basal) in cortical and hippocampal neurons in both sexes. Sholl analysis also revealed a decrease in dendritic intersections in the cortex and hippocampus, indicating reduced dendritic arborization. <b>Conclusions:</b> This study provides evidence that neonatal CBD exposure perturbs normal brain development and leads to lasting alterations in spatial memory and neuronal dendrite morphology in early adulthood, with sex-dependent sensitivity.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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