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":"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":"236-246"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","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}
{"title":"<i>Letter to the Editor:</i> Regarding Ogunsola et al.","authors":"Seyed Ehsan Mousavi","doi":"10.1089/can.2024.0144","DOIUrl":"10.1089/can.2024.0144","url":null,"abstract":"","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e373-e374"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969737","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}
Pavel Powlowski, Justin Matheson, Bernard Le Foll, Ana C Andreazza, Ruth A Ross
{"title":"Acute Cannabis Administration Transiently Reduces Mitochondrial DNA in Young Adults: Findings from a Secondary Analysis of a Double-Blind, Placebo-Controlled, Randomized Clinical Trial.","authors":"Pavel Powlowski, Justin Matheson, Bernard Le Foll, Ana C Andreazza, Ruth A Ross","doi":"10.1089/can.2023.0282","DOIUrl":"10.1089/can.2023.0282","url":null,"abstract":"<p><p><b>Background:</b> Cannabis is one of the world's most commonly used substances; however, many questions remain unanswered as to how cannabis impacts the body. Recently, there has been a resurgence of research into the effects of plant-derived cannabinoids on mitochondrial health. In particular, a number of studies implicate mitochondrial-Δ9-tetrahydrocannabinol (Δ9-THC) interactions with altered memory, metabolism, and catalepsy in mice. Although the research in this field is expanding rapidly, there is little known about the effects of cannabis on mitochondria health in human subjects either in acute or chronic term use. <b>Methods:</b> Blood samples were obtained from a double-blind, placebo-controlled, parallel-group randomized clinical trial in which adults who regularly use cannabis (1-4 days/week) aged 19-25 years were randomized 2:1 to receive either an active (12.5% Δ9-THC) cigarette or placebo (<0.01% Δ9-THC) cigarette containing 750 mg of cannabis before driving simulator testing. DNA was extracted from whole blood using commercial spin columns, followed by measurement of mt-ND1, mt-ND4, and β2M using quantitative polymerase chain reaction. One-way repeated measures analysis of variance (ANOVA) followed by Dunnett's multiple comparisons test was used to observe changes in mitochondrial DNA (mtDNA) copy number over time. A two-tailed Pearsons R test was used to assess correlations between mtDNA copy number and cannabinoid levels (Δ9-THC and metabolites) in blood. <b>Results:</b> We found that exposure to active cannabis containing Δ9-THC, as opposed to placebo, was associated with an acute reduction in mitochondrial DNA copy number in whole blood at 15 min and 1 h after smoking. The observed decrease in mtDNA copy number negatively correlated with blood concentrations of 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH), the two primary metabolites of Δ9-THC, but not Δ9-THC itself. Further, the negative correlation between 11-OH THC and THC-COOH concentrations and mtDNA copy number was found in only a subgroup of participants who use cannabis infrequently, suggesting a tolerance effect. <b>Conclusions:</b> These results illuminate mitochondrial alterations attributed to Δ9-THC consumption, which may be mediated by metabolites. These results appear to suggest stronger effects in individuals who consume cannabis less frequently, suggesting some form of tolerance to the effects of Δ9-THC and its metabolites on mtDNA content in whole blood. <b>Keywords:</b> Mitochondria; mtDNA; cannabis; THC; THC metabolites; blood; THC-COOH; 11-OH-THC.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e314-e322"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455462","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}
Lawrance D Mullen, E Dale Hart, Svante Vikingsson, Ruth E Winecker, Eugene Hayes, Ron Flegel, Lisa D Davis, Eric R Welsh, Mahmoud ElSohly, Waseem Gul, Tim Murphy, Iram Shahzadi, Kareem ElSohly, Edward J Cone
{"title":"Stability of Nano-Emulsified Cannabidiol in Acidic Foods and Beverages.","authors":"Lawrance D Mullen, E Dale Hart, Svante Vikingsson, Ruth E Winecker, Eugene Hayes, Ron Flegel, Lisa D Davis, Eric R Welsh, Mahmoud ElSohly, Waseem Gul, Tim Murphy, Iram Shahzadi, Kareem ElSohly, Edward J Cone","doi":"10.1089/can.2024.0064","DOIUrl":"10.1089/can.2024.0064","url":null,"abstract":"<p><p><b>Introduction:</b> Food and beverage products containing cannabidiol (CBD) is a growing industry, but some CBD products contain Δ<sup>9</sup>-tetrahydrocannabinol (Δ<sup>9</sup>-THC), despite being labeled as \"THC-free\". As CBD can convert to Δ<sup>9</sup>-THC under acidic conditions, a potential cause is the formation of Δ<sup>9</sup>-THC during storage of acidic CBD products. In this study, we investigated if acidic products (pH ≤ 4) fortified with CBD would facilitate conversion to THC over a 2-15-month time period. <b>Materials and Methods:</b> Six products, three beverages (lemonade, cola, and sports drink) and three condiments (ketchup, mustard, and hot sauce), were purchased from a local grocery store and fortified with a nano-emulsified CBD isolate (verified as THC-free by testing). The concentrations of CBD and Δ<sup>9</sup>-THC were measured by Gas Chromatography Flame Ionization Detector (GC-FID) and Liquid Chromatography with tandem mass spectrometry (LC-MS/MS), respectively, for up to 15 months at room temperature. <b>Results:</b> Coefficients of variation (CVs) of initial CBD concentrations by GC-FID were <10% for all products except ketchup (18%), showing homogeneity in the fortification. Formation of THC was variable, with the largest amount observed after 15 months in fortified lemonade #2 (3.09 mg Δ<sup>9</sup>-THC/serving) and sports drink #2 (1.18 mg Δ<sup>9</sup>-THC/serving). Both beverages contain citric acid, while cola containing phosphoric acid produced 0.10 mg Δ<sup>9</sup>-THC/serving after 4 months. The importance of the acid type was verified using acid solutions in water. No more than 0.01 mg Δ<sup>9</sup>-THC/serving was observed with the condiments after 4 months. <b>Discussion:</b> Conversion of CBD to THC can occur in some acidic food products when those products are stored at room temperature. Therefore, despite purchasing beverages manufactured with a THC-free nano-emulsified form of CBD, consumers might be at some risk of unknowingly ingesting small amounts of THC. The results indicate that up to 3 mg Δ<sup>9</sup>-THC from conversion can be present in a serving of CBD-lemonade. Based on the previous studies, 3 mg Δ<sup>9</sup>-THC might produce a positive urine sample (≥15 ng/mL THC carboxylic acid) in some individuals. <b>Conclusion:</b> Consumers must exert caution when consuming products with an acidic pH (≤4) that suggests that they are \"THC-Free,\" because consumption might lead to positive drug tests or, in the case of multiple doses, intoxication.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"213-219"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417900","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}
Erin Johnson, Michael Kilgore, Paul Nuzzo, Shanna Babalonis
{"title":"Minor Cannabinoid Profile of Unregulated Cannabidiol Products.","authors":"Erin Johnson, Michael Kilgore, Paul Nuzzo, Shanna Babalonis","doi":"10.1089/can.2024.0058","DOIUrl":"10.1089/can.2024.0058","url":null,"abstract":"<p><p><b>Background:</b> Although the majority of cannabinoid research has focused on delta-9-tetrahydrocannabinol (Δ<sup>9</sup>-THC) and cannabidiol (CBD), there is increasing interest in the therapeutic effects of other phytocannabinoid compounds (i.e., minor cannabinoids), as there is little known about their effects or interaction with CBD. The current study objective was to determine the concentrations of 15 minor cannabinoids in unregulated, over-the-counter CBD products. <b>Methods:</b> A cross-section sample of 80 local and national brands of hemp-derived oil products was purchased both online and in local retail outlets in central Kentucky. Epidiolex® was included as a regulated control. Samples from each product were extracted by solvent extraction and quantified by liquid-chromatography tandem mass-spectrometry. The targeted cannabinoids were: cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabidivarinic acid, Δ<sup>9</sup>-tetrahydrocannabivarin, Δ<sup>9</sup>-tetrahydrocannabivarinic acid, Δ<sup>9</sup>-tetrahydrocannabinolic acid-A, Δ<sup>8</sup>-tetrahydrocannabinol (Δ<sup>8</sup>-THC), cannabigerol (CBG), cannabigerolic acid, cannabinol (CBN), cannabinolic acid, cannabicyclol (CBL), cannabicyclolic acid, cannabichromene (CBC) and cannabichromenic acid. <b>Results:</b> Among the unregulated products included in this analysis, the most frequently detected minor cannabinoids were CBDV (100% of samples tested), CBG (77%), CBC (72%), CBN (67%), CBL (67%), and CBDA (51%). Δ<sup>8</sup>-THC was not detected in any of the products tested. Concentrations of these cannabinoids varied widely from trace concentrations to several mg/mL (e.g., CBDA: 0.006-12.258 mg/mL). <b>Conclusions:</b> These data indicate CBD products often contain minor cannabinoids, although the array and concentrations of these cannabinoids vary widely across products. The concentrations of these minor cannabinoids are largely absent from product labels, leaving consumers uninformed about product contents.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"220-227"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543868","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}
Harrison J Elder, C Austin Zamarripa, McKenna Klausner, Joseph Wakshlag, Robert Davis, Beth Dresser, Christian Kjaer, Elise M Weerts, Ryan Vandrey, Tory R Spindle
{"title":"The Pharmacokinetics and Pharmacodynamics of a Hemp-Derived \"Full-Spectrum\" Oral Cannabinoid Product with a 1:1 Ratio of Cannabidiol to Cannabidiolic Acid and Delta-9-Tetrahydrocannabinol to Delta-9-Tetrahydrocannabinolic Acid: A Double-Blind, Placebo-Controlled, Within-Subjects Human Laboratory Study.","authors":"Harrison J Elder, C Austin Zamarripa, McKenna Klausner, Joseph Wakshlag, Robert Davis, Beth Dresser, Christian Kjaer, Elise M Weerts, Ryan Vandrey, Tory R Spindle","doi":"10.1089/can.2024.0187","DOIUrl":"10.1089/can.2024.0187","url":null,"abstract":"<p><p><b>Aim:</b> To examine the acute pharmacokinetics (PK) and pharmacodynamics (PD) of a patented oral cannabinoid product containing a botanical hemp-derived \"full-spectrum\" extract with an approximate 1:1 ratio of cannabidiol (CBD) to cannabidiolic acid (CBDA) and delta-9-tetrahydrocannabinol (THC) to delta-9-tetrahydrocannabinolic acid (THCA). <b>Methods:</b> Healthy adults (<i>n</i> = 15) ingested soft gels containing 0 (placebo), and approximately 1, 2, and 4 mg/kg of total cannabinoids (combination of CBD, CBDA, THC, THCA, and other minor cannabinoids) in an ascending-dose order in four experimental sessions separated by ≥1 week (the placebo condition occurred randomly within the dose sequence). Mean doses (mg) of primary cannabinoids in the active drug conditions were: 1 mg/kg condition (CBD = 41.1, CBDA = 43.7, THC = 2.2, THCA = 1.6), 2 mg/kg condition (CBD = 73.4, CBDA = 77.9, THC = 3.9, THCA = 2.9), and 4 mg/kg condition (CBD = 134.5, CBDA = 142.8, THC = 7.2, THCA = 5.3). PD outcomes (subjective, cognitive, and physiological effects) were measured before and repeatedly for 8 h after dosing. Plasma specimens were collected throughout the 8-h sessions and at 24- and 48-h post-dosing. PK outcomes included peak plasma concentration (<i>C</i><sub>max</sub>) and time to maximum concentration (<i>T</i><sub>max</sub>). <b>Results:</b> For PD outcomes, few differences were observed between 1 mg/kg and placebo. However, relative to placebo, 2 mg/kg and 4 mg/kg produced small to moderate increases in subjective drug effects, including abuse liability items (e.g., \"like\"), and 4 mg/kg also impaired working memory performance. Generally, PD effects peaked 3-5 h post-dosing and returned to baseline by 8 h. Dose-orderly increases in <i>C</i><sub>max</sub> were observed for CBD, CBDA, THC, THCA, and their respective metabolites (e.g., 7-COOH-CBD, THCCOOH), which were often detectable 48 h post-dosing. Across all doses, <i>C</i><sub>max</sub> for CBDA and THCA was 19-25-fold higher and <i>T</i><sub>max</sub> was up to 2-fold earlier compared with CBD and THC, respectively. <b>Conclusions:</b> Acute administration of a \"full-spectrum\" hemp-derived cannabinoid product produced dose-orderly effects; the highest dose elicited several adverse events and produced moderate cognitive impairment and subjective intoxication, despite containing a relatively low dose of THC (mean: 7.2 mg). Carboxylated cannabinoids (e.g., CBDA) exhibited substantially greater bioavailability and faster absorption compared with decarboxylated cannabinoids (e.g., CBD). Additional systematic research is needed to characterize how constituent profile impacts the effects of cannabinoid products, and more studies directly comparing carboxylated and decarboxylated compounds appear warranted.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e299-e313"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555867","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}
Daisy Flores-Cortez, Eduardo Villalobos-Pacheco, Cecilia Ignacio-Punin, Guiselle Gutierrez-Guerra, Javier Tovar-Brandan, Juan Rodriguez-Tafur
{"title":"Hepatoprotective Effect of Cannabidiol on the Progression of Experimental Hepatic Cirrhosis in Rats.","authors":"Daisy Flores-Cortez, Eduardo Villalobos-Pacheco, Cecilia Ignacio-Punin, Guiselle Gutierrez-Guerra, Javier Tovar-Brandan, Juan Rodriguez-Tafur","doi":"10.1089/can.2023.0285","DOIUrl":"10.1089/can.2023.0285","url":null,"abstract":"<p><p><b>Introduction:</b> Liver cirrhosis is a condition characterized by the gradual replacement of normal liver tissue with scar tissue, ultimately leading to liver failure. This slow and progressive disease begins with a chronic inflammatory process induced by a noxious agent. In its advanced stages, the disease lacks effective therapies. Research has demonstrated the significant involvement of the endocannabinoid system in the pathogenesis of this disease. This study evaluated the hepatoprotective effect of cannabidiol (CBD) in the progression of experimental hepatic cirrhosis induced by thioacetamide (TAA) in rats. <b>Methods:</b> A randomized experimental design was employed using Holtzman rats. Hepatic cirrhosis was induced by intraperitoneal administration of TAA at a dose of 150 mg/kg for 6 weeks, with treatment initiated additionally. The groups were as follows: Group 1: TAA + vehicle; Group 2: TAA + CBD 2 mg/kg; Group 3: TAA + CBD 9 mg/kg; Group 4: TAA + CBD 18 mg/kg; Group 5: TAA + silymarin 50 mg/kg; and Group 6: Healthy control. Serum biochemical analysis (total bilirubin, direct bilirubin, ALT, AST, alkaline phosphatase, and albumin) and hepatic histopathological study were performed. The Knodell histological activity index (HAI) was determined, considering periportal necrosis, intralobular degeneration, portal inflammation, fibrosis, and focal necrosis. <b>Results:</b> All groups receiving TAA exhibited an elevation in AST levels; however, only those treated with CBD at doses of 2 mg/kg and 18 mg/kg did not experience significant changes compared to their baseline values (152.8 and 135.7 IU/L, respectively). Moreover, ALT levels in animals treated with CBD showed no significant variation compared to baseline. The HAI of hepatic tissue was notably lower in animals treated with CBD at doses of 9 and 18 mg/kg, scoring 3.0 and 3.25, respectively, in contrast to the TAA + vehicle group, which recorded a score of 7.00. Animals treated with CBD at 18 mg/kg showed a reduced degree of fibrosis and necrosis compared to those receiving TAA alone (<i>p</i> ≤ 0.05). <b>Conclusion:</b> Our findings demonstrate that cannabidiol exerts a hepatoprotective effect in the development of experimental hepatic cirrhosis induced in rats.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"228-235"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417899","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}
{"title":"When Public Will Meets Legislative Resistance: Five Lessons from Ohio's Issue 2 Cannabis Legalization Controversy.","authors":"Bryant M Stone","doi":"10.1089/can.2024.0022","DOIUrl":"10.1089/can.2024.0022","url":null,"abstract":"<p><p>In this paper, I explore the challenges of legalizing cannabis in Ohio, focusing on the passing of the Issue 2 Bill, legislative resistance, and public response. I propose five strategies for effective policy change: persistent advocacy post policy change success, establishing strong coalitions, empowering grassroots movements, promoting rigorous data-driven research, and launching public education campaigns. I offer a detailed analysis of the interaction between public opinion and legislative action in cannabis legalization and its implications for substance-related policy change.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e371-e372"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140286993","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}
{"title":"Cannabidiol Enhances the Anticancer Activity of Etoposide on Prostate Cancer Cells.","authors":"Yalcin Erzurumlu, Deniz Catakli","doi":"10.1089/can.2023.0284","DOIUrl":"10.1089/can.2023.0284","url":null,"abstract":"<p><p><b>Introduction:</b> <i>Cannabis sativa</i> extract has been used as an herbal medicine since ancient times. It is one of the most researched extracts, especially among supportive treatments against cancer. Prostate cancer is one of the most frequently diagnosed cancer types in men worldwide and an estimated 288,300 new cases were diagnosed in 2023. Today, many advanced therapeutic approaches are used for prostate cancer, such as immunotherapy and chemotherapy, but acquired drug resistance, long-term drug usage and differentiation of cancer cells mostly restricted the efficiency of therapies. Therefore, it is thought that the use of natural products to overcome these limitations and improve the effectiveness of existing therapies may offer promising approaches. The present study focused on the investigation of the possible enhancer role of cannabidiol (CBD), which is a potent ingredient compound of Cannabis, on the chemotherapeutic agent etoposide in prostate cancer cells. <b>Methods:</b> Herein, we tested the potentiator role of CBD on etoposide in prostate cancer cells by testing the cytotoxic effect, morphological alterations, apoptotic effects, autophagy, unfolded protein response (UPR) signaling, endoplasmic reticulum-associated degradation mechanism (ERAD), angiogenic and androgenic factors, and epithelial-mesenchymal transition (EMT). In addition, we examined the combined treatment of CBD and etoposide on colonial growth, migrative, invasive capability, 3D tumor formation, and cellular senescence. <b>Results:</b> Our findings demonstrated that cotreatment of etoposide with CBD importantly suppressed autophagic flux and induced ERAD and UPR signaling in LNCaP cells. Also, CBD strongly enhanced the etoposide-mediated suppression of androgenic signaling, angiogenic factor VEGF-A, protooncogene c-Myc, EMT, and also induced apoptosis through activation caspase-3 and PARP-1. Moreover, coadministration markedly decreased tumorigenic properties, such as proliferative capacity, colonial growth, migration, and 3D tumor formation and also induced senescence. Altogether, our data revealed that CBD has a potent enhancer effect on etoposide-associated anticancer activities. <b>Conclusion:</b> The present study suggests that the use of CBD as a supportive therapy in existing chemotherapeutic approaches may be a promising option, but this effectiveness needs to be investigated on a large scale.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"258-276"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003685","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}
Avneet Kaur, Ishandeep Singh, Isha Kohli, Sahiljot Singh Bhupal, Jay Patel, Nikki Nikzad, Aalam Sohal, Juliana Yang
{"title":"Association of Cannabis Use with Complications Among Patients with Gastroesophageal Reflux Disease: Insights from National Inpatient Sample.","authors":"Avneet Kaur, Ishandeep Singh, Isha Kohli, Sahiljot Singh Bhupal, Jay Patel, Nikki Nikzad, Aalam Sohal, Juliana Yang","doi":"10.1089/can.2024.0011","DOIUrl":"10.1089/can.2024.0011","url":null,"abstract":"<p><p><b>Background/Objective:</b> Cannabis, one of the most widely used recreational drug in the United States, has had a significant surge in usage following its legalization in 1996. In recent years, there has been research into the physiological effects of cannabis on the gastrointestinal (GI) system. Our study aims to systematically examine the association between cannabis use and complications of gastroesophageal reflux disease (GERD). <b>Materials and Methods:</b> We queried the 2016-2020 National Inpatient Sample database to identify patient encounters with GERD. Patients with eosinophilic esophagitis or missing demographics were excluded. We compared patient demographics, comorbidities, and complications among cannabis users and nonusers. Multivariate logistic regression analysis was used to investigate the relationship between cannabis use and complications of GERD. <b>Results:</b> A total of 27.2 million patient encounters were included in the analysis, out of which 507,190 were cannabis users. Majority of the cannabis users were aged between 45-64 years (46.6%), males (57.4%), White (63.84%), and belonged to the lowest income quartile (40.6%). Cannabis users demonstrated a higher prevalence of esophagitis compared to nonusers (6.11% vs. 3.23%, <i>p</i><0.001). However, they exhibited a lower rates of esophageal stricture (0.6% vs. 0.8%, <i>p</i><0.001) and esophageal cancer (0.2% vs. 0.24%, <i>p</i><0.001). After adjusting for confounding factors, cannabis users were noted to have higher odds of esophagitis (adjusted odds ratio [aOR]: 1.34, 95% confidence interval [CI]: 1.30-1.39, <i>p</i><0.001). A lower odds of esophageal stricture (aOR: 0.88, 95% CI: 0.81-0.96, <i>p</i>=0.02) and esophageal cancer (aOR: 0.48,95% CI: 0.42-0.57, <i>p</i><0.001) were noted. <b>Conclusion:</b> Our cross-sectional study using the nationally available database indicates an association between cannabis use and higher odds of esophagitis, along with lower odds of esophageal stricture and cancer. While these findings suggest a potential relationship between cannabis use and esophageal complications, it is limited in establishing causality. Therefore, further long-term studies are warranted to understand the mechanism behind this association and to determine if cannabis use has an impact on esophagus.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e333-e340"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856023","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}