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Beneficial Consequences of One-Month Oral Treatment with Cannabis Oil on Cardiac Hypertrophy and the Mitochondrial Pool in Spontaneously Hypertensive Rats. 口服一个月大麻油对自发性高血压大鼠心肌肥厚和线粒体池的有益影响
IF 3.1 4区 医学
Cannabis and Cannabinoid Research Pub Date : 2025-02-01 Epub Date: 2024-08-13 DOI: 10.1089/can.2024.0066
Erica Vanesa Pereyra, Joshua Godoy Coto, Jorge Omar Velez Rueda, Fiorella Anabel Cavalli, Luisa Fernanda González Arbelaez, Juliana Catalina Fantinelli, Oswaldo Aranda, Jorge Esteban Colman Lerner, Enrique Leo Portiansky, Susana Maria Mosca, Irene Lucia Ennis
{"title":"Beneficial Consequences of One-Month Oral Treatment with Cannabis Oil on Cardiac Hypertrophy and the Mitochondrial Pool in Spontaneously Hypertensive Rats.","authors":"Erica Vanesa Pereyra, Joshua Godoy Coto, Jorge Omar Velez Rueda, Fiorella Anabel Cavalli, Luisa Fernanda González Arbelaez, Juliana Catalina Fantinelli, Oswaldo Aranda, Jorge Esteban Colman Lerner, Enrique Leo Portiansky, Susana Maria Mosca, Irene Lucia Ennis","doi":"10.1089/can.2024.0066","DOIUrl":"10.1089/can.2024.0066","url":null,"abstract":"<p><p><b>Introduction:</b> It has been demonstrated the dysregulation of the cardiac endocannabinoid system in cardiovascular diseases. Thus, the modulation of this system through the administration of phytocannabinoids present in medicinal cannabis oil (CO) emerges as a promising therapeutic approach. Furthermore, phytocannabinoids exhibit potent antioxidant properties, making them highly desirable in the treatment of cardiac pathologies, such as hypertension-induced cardiac hypertrophy (CH). <b>Objective:</b> To evaluate the effect of CO treatment on hypertrophy and mitochondrial status in spontaneously hypertensive rat (SHR) hearts. <b>Methods:</b> Three-month-old male SHR were randomly assigned to CO or olive oil (vehicle) oral treatment for 1 month. We evaluated cardiac mass and histology, mitochondrial dynamics, membrane potential, area and density, myocardial reactive oxygen species (ROS) production, superoxide dismutase (SOD), and citrate synthase (CS) activity and expression. Data are presented as mean ± SEM (n) and compared by <i>t</i>-test, or two-way ANOVA and Bonferroni <i>post hoc</i> test were used as appropriate. <i>p</i> < 0.05 was considered statistically significant. <b>Results:</b> CH was reduced by CO treatment, as indicated by the left ventricular weight/tibia length ratio, left ventricular mass index, myocyte cross-sectional area, and left ventricle collagen volume fraction. The ejection fraction was preserved in the CO-treated group despite the persistence of elevated systolic blood pressure and the reduction in CH. Mitochondrial membrane potential was improved and mitochondrial biogenesis, dynamics, area, and density were all increased by treatment. Moreover, the activity and expression of the CS were enhanced by treatment, whereas ROS production was decreased and the antioxidant activity of SOD increased by CO administration. <b>Conclusion:</b> Based on the mentioned results, we propose that 1-month oral treatment with CO is effective to reduce hypertrophy, improve the mitochondrial pool and increase the antioxidant capacity in SHR hearts.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e134-e144"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975124","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
The Endocannabinoid System as a Target for Ischemic Stroke Therapy. 内源性大麻素系统作为缺血性卒中治疗的靶点。
IF 3.1 4区 医学
Cannabis and Cannabinoid Research Pub Date : 2025-02-01 DOI: 10.1089/can.2024.0017
Solange de Souza Stork, Khiany Mathias, David Dos Santos, Fabrício Weinheimer Lippert, Richard Simon Machado, Victor Duílio Maragno, Larissa Joaquim, Samara Souza Stork, Rafael Mariano Bitencourt, Franciane Bobinski, Fabricia Petronilho
{"title":"The Endocannabinoid System as a Target for Ischemic Stroke Therapy.","authors":"Solange de Souza Stork, Khiany Mathias, David Dos Santos, Fabrício Weinheimer Lippert, Richard Simon Machado, Victor Duílio Maragno, Larissa Joaquim, Samara Souza Stork, Rafael Mariano Bitencourt, Franciane Bobinski, Fabricia Petronilho","doi":"10.1089/can.2024.0017","DOIUrl":"10.1089/can.2024.0017","url":null,"abstract":"<p><p><b>Introduction:</b> Cannabinoids are increasingly being explored as a potential treatment for neurodegenerative diseases. This article aims to provide a narrative review of available data on the treatment of neurological disorders with cannabis constituents, focusing on ischemic stroke. <b>Methods:</b> Selected articles are summarized to describe design, results, limitations, conclusions, and implications about this theme. <b>Results:</b> The growing understanding of the endocannabinoid system and the cannabinoid receptors distribution in all human body systems and organs and particularly in brain structures importantly involved in myelination processes, suggests potential benefits for stroke symptoms and overall patient improvement. However, the variety of studied compounds, the different administration routes, dosages, and timing complicates data comparison, especially due to limited studies about these compounds, peculiarly in stroke patients. Thereat, this review to showcase disparities in findings and to summarize current advancements in cannabinoid use for potential future treatments. <b>Conclusion:</b> This article offers a review of the current literature in the field and discuss a pragmatic approach to the clinical use of cannabinoids in patients with ischemic stroke.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":"10 1","pages":"38-52"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416688","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
The Cannabis Gray Market: A Case for Cannabis Regulatory Science Research. 大麻灰色市场:大麻监管科学研究案例。
IF 3.1 4区 医学
Cannabis and Cannabinoid Research Pub Date : 2025-02-01 Epub Date: 2024-07-01 DOI: 10.1089/can.2023.0278
Nicolas J Schlienz, Nicholas J Felicione, Dustin C Lee, Richard J O'Connor, Danielle M Smith
{"title":"The Cannabis Gray Market: A Case for Cannabis Regulatory Science Research.","authors":"Nicolas J Schlienz, Nicholas J Felicione, Dustin C Lee, Richard J O'Connor, Danielle M Smith","doi":"10.1089/can.2023.0278","DOIUrl":"10.1089/can.2023.0278","url":null,"abstract":"<p><p>The cannabis gray market poses significant public health concerns and remains a major threat to consumer and/or potential consumer uptake of regulated cannabis markets in jurisdictions with legal state-sponsored cannabis programs. In this perspective, we provide an overview of the cannabis gray market, and describe an integrated epidemiological and regulatory science framework to study the gray market. Using tobacco regulatory science as a guide, we introduce example cannabis regulatory science research activities as a means to improve the field's understanding of the cannabis gray market. Cannabis regulatory science is a developing field that can improve our understanding of the cannabis regulatory ecosystem and provide regulatory officials and policymakers alike with much needed data to inform regulatory decision-making and improve the success and uptake of state-sponsored cannabis programs.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"6-10"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466331","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 : 2025-02-01 Epub 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":"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":"e145-e155"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","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
Does the Quantification of Δ9-Tetrahydrocannabinolic Acid A in Serum/Plasma Provide Any Additional Information About Consumption Pattern from Drivers Under the Influence of Cannabis? 血清/血浆中 Δ9-Tetrahydrocannabolic Acid A 的定量是否提供了有关受大麻影响的驾驶员消费模式的额外信息?
IF 3.1 4区 医学
Cannabis and Cannabinoid Research Pub Date : 2025-02-01 Epub Date: 2024-03-21 DOI: 10.1089/can.2023.0172
Lisa Höfert, Sven Baumann, Jan Dreßler, Susen Becker
{"title":"Does the Quantification of Δ9-Tetrahydrocannabinolic Acid A in Serum/Plasma Provide Any Additional Information About Consumption Pattern from Drivers Under the Influence of Cannabis?","authors":"Lisa Höfert, Sven Baumann, Jan Dreßler, Susen Becker","doi":"10.1089/can.2023.0172","DOIUrl":"10.1089/can.2023.0172","url":null,"abstract":"<p><p><b>Introduction:</b> Δ9-tetrahydrocannabinolic acid A (THCA-A) is one of the main ingredients of cannabis plants and is converted to the psychoactive substance Δ9-tetrahydrocannabinol (THC) by decarboxylation during heating above ∼90°C. During the consumption of cannabis, a varying proportion of THCA-A is absorbed into the body. Therefore, the quantification of THCA-A in serum/plasma might provide additional information on consumption behavior in driving under the influence of cannabis cases. <b>Materials and Methods:</b> In this study, an already established gas-chromatography mass-spectrometry (GC-MS) method for the quantification of THC, 11-OH-THC, and THC-COOH in serum and plasma samples was extended to include THCA-A. This validated method was then applied to 1228 routinely achieved serum/plasma samples from drivers suspected of cannabis consumption in Western Saxony. Two different grouping systems for chronic/occasional consumption, one system for acute/subacute consumption, Huestis formulas, and the cannabis influence factor (CIF) were used for evaluation. <b>Results:</b> Method validation showed appropriate results for forensic toxicological routine analysis. Limit of detection and lower limit of quantification (LLOQ) for THCA-A were 0.3 and 1.0 ng/mL, respectively. Reproducibility was <11% and accuracy ranged between 104% and 107%. THCA-A was stable in native samples at least for 2 weeks at room temperature or 4°C as well as 1 month at -20°C. Freeze-thaw stability for three cycles and processed sample stability over 3 days was proven. A total of 865 cases with a THC concentration above the German analytical cutoff of 1 ng/mL as well as the analytical LLOQs of 0.9 and 2.5 ng/mL for 11-OH-THC and THC-COOH, respectively, were included in further statistical analysis. In 407 (47.1%) of these samples, THCA-A was quantifiable. Different statistical analyses indicated a correlation between THCA-A and THC concentrations in cases of chronic and acute consumption. In addition, an increase of chronic and acute cases with increasing THCA-A concentrations was observed. However, no correlation between THCA-A and CIF was found. <b>Discussion:</b> These data show that THCA-A might be an additional indicative marker to provide information about consumption frequency and acuteness. Additional studies with known consumption frequencies and times are required to verify these findings.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e165-e175"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140183837","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
Investigating the Relationship Between Cannabis Expectancies and Anxiety, Depression, and Pain Responses After Acute Flower and Edible Cannabis Use. 研究急性吸食花大麻和食用大麻后,大麻预期与焦虑、抑郁和疼痛反应之间的关系。
IF 3.1 4区 医学
Cannabis and Cannabinoid Research Pub Date : 2025-02-01 Epub Date: 2024-04-12 DOI: 10.1089/can.2023.0264
Margy Y Chen, Emily B Kramer, Laurel P Gibson, L Cinnamon Bidwell, Kent E Hutchison, Angela D Bryan
{"title":"Investigating the Relationship Between Cannabis Expectancies and Anxiety, Depression, and Pain Responses After Acute Flower and Edible Cannabis Use.","authors":"Margy Y Chen, Emily B Kramer, Laurel P Gibson, L Cinnamon Bidwell, Kent E Hutchison, Angela D Bryan","doi":"10.1089/can.2023.0264","DOIUrl":"10.1089/can.2023.0264","url":null,"abstract":"<p><p><b>Objective:</b> Cannabis has been touted for a host of pharmacological and therapeutic effects and users commonly report reduced symptoms of physical and mental health conditions, including anxiety, depression, and chronic pain. While there is existing empirical evidence supporting these effects of cannabis use, little is known about the extent to which these effects result from pharmacological versus expectancy factors. We evaluated the associations between participants' cannabis expectancies and their acute self-reported reactions after using legal market forms of cannabis with varying levels of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) in three domains: anxiety, depression, and pain. <b>Methods:</b> Fifty-five flower and 101 edible cannabis users were randomly assigned and asked to purchase at a local dispensary one of three products containing varying levels of CBD and THC. Participants completed a baseline assessment where they reported expectancies about general health effects of cannabis use and an experimental mobile laboratory assessment where they administered their assigned products. Edible users also reported their domain-specific expectancies about cannabis use in improving anxiety, depression, and pain. Following administration, participants completed acute indicators of anxiety, depression, and pain operationalized through subjective acute tension, elation, and a single-item measure of pain. <b>Results:</b> Among flower users, more positive expectancies for cannabis to improve general health were correlated with greater reductions in tension at acute post-use. This finding was replicated among edible users. Unlike flower users, more positive expectancies for cannabis to improve general health were also correlated with greater increases in elation and greater reductions in pain among edible users. More positive expectancies for cannabis to improve depression and pain were also correlated with greater increases in elation and greater reductions in pain, respectively, among edible users. <b>Conclusions:</b> Cannabis users' expectancies significantly impacted some of the acute subjective effects of legal market cannabis products. Among both flower and edible users, consistent, significant expectancy effects were found. Results were consistent with prior findings and demonstrate the need to measure and control pre-existing expectancies in future research that involves cannabis administration. Clinical trial registration number: NCT03522103.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"71-80"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847871","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
Activation of CB2 Receptors by (-)-Cannabichromene but Not (+)-Cannabichromene. (-)-Cannabichromene 对 CB2 受体的激活而非 (+)-Cannabichromene 对 CB2 受体的激活。
IF 3.1 4区 医学
Cannabis and Cannabinoid Research Pub Date : 2025-02-01 Epub Date: 2024-08-13 DOI: 10.1089/can.2023.0212
Michael Udoh, Marina Santiago, Syed Haneef, Alison Rodger, Charles K Marlowe, Philip J Barr, Mark Connor
{"title":"Activation of CB2 Receptors by (-)-Cannabichromene but Not (+)-Cannabichromene.","authors":"Michael Udoh, Marina Santiago, Syed Haneef, Alison Rodger, Charles K Marlowe, Philip J Barr, Mark Connor","doi":"10.1089/can.2023.0212","DOIUrl":"10.1089/can.2023.0212","url":null,"abstract":"<p><p><b>Introduction:</b> Cannabichromene (CBC) is a minor constituent of cannabis that is a selective cannabinoid CB2 receptor agonist and activator of TRPA1. To date, it has not been shown whether (-)-CBC, (+)-CBC, or both can mediate these effects. In this study, we investigate the activity of the CBC enantiomers at CB1, CB2, and Transient receptor potential ankyrin 1 (TRPA1) receptors <i>in vitro</i>. <b>Materials and Methods:</b> CBC enantiomers were purified from synthetic CBC by chiral chromatography, and their optical activity was confirmed by spectroscopy. Human CB1 and CB2 receptor activity was measured using a fluorescent assay of membrane potential in stably transfected AtT20 cells. TRPA1 activation was measured using a fluorescent assay of intracellular calcium in stably transfected HEK293 cells. <b>Results:</b> The (-)-CBC activated CB2 with an EC<sub>50</sub> of 1.5 µM, to a maximum of 60% of (-)CP55940. (+)-CBC did not activate CB2 at concentrations up to 30 µM. Only 30 µM (-)-CBC produced detectable activation of CB1, (+)-CBC was inactive. Both (-)-CBC and (+)-CBC activated TRPA1; at 30 µM (-)-CBC produced an activation 50% of that of the reference agonist cinnamaldehyde (300 µM), 30 µM (+)-CBC activated TRPA1 to 38% of the cinnamaldehyde maximum. <b>Discussion:</b> It is unclear whether (-)-CBC is the sole or even the predominant enantiomer of CBC enzymatically synthesized in cannabis. This study shows that (-)-CBC is the active isomer at CB2 receptors, while both isomers activate TRPA1. The results suggest that medicinal preparations of CBC that target cannabinoid receptors would be most effective when (-)-CBC is the dominant isomer.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e94-e101"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975123","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
Tetrahydrocannabivarin is Not Tetrahydrocannabinol. 四氢大麻酚不是四氢大麻酚。
IF 3.1 4区 医学
Cannabis and Cannabinoid Research Pub Date : 2025-02-01 Epub Date: 2024-07-12 DOI: 10.1089/can.2024.0051
Mehdi Haghdoost, Erica N Peters, Matthew Roberts, Marcel O Bonn-Miller
{"title":"Tetrahydrocannabivarin is Not Tetrahydrocannabinol.","authors":"Mehdi Haghdoost, Erica N Peters, Matthew Roberts, Marcel O Bonn-Miller","doi":"10.1089/can.2024.0051","DOIUrl":"10.1089/can.2024.0051","url":null,"abstract":"<p><p>Tetrahydrocannabivarin (THCV) is a phytocannabinoid that is becoming popular across the North American cannabis market. THCV has been reported to reduce blood sugar and act as an appetite suppressant in several independent pre-clinical studies, which has earned it the popular nickname of \"diet weed,\" despite few human studies of these effects. Additionally, THCV is usually and incorrectly categorized as an intoxicating analogue of tetrahydrocannabinol (THC), which causes confusion among both consumers and regulators. In this article, we examine what is known pre-clinically and clinically about THCV, as well as highlight mechanisms of action, in order to clarify the scientific differences between THCV and THC. THCV, although structurally similar to THC, has distinct pharmacological activity and physiological effects at the doses currently reported in the literature. We highlight areas of opportunity for further THCV research in order to determine the full and appropriate potential for unique health, wellness, and therapeutic applications of this compound.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"1-5"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141598534","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
Combined Endocannabinoid and Cyclooxygenase Inhibition Additively Attenuates Post-Surgical Pain. 内源性大麻素联合环加氧酶抑制可减轻术后疼痛。
IF 3.1 4区 医学
Cannabis and Cannabinoid Research Pub Date : 2025-02-01 Epub Date: 2025-02-03 DOI: 10.1089/can.2024.0088
Carl E B Rodriguez, S Olivia Vanegas, A Matthew Reck, Yasmin Schrom, Steven G Kinsey
{"title":"Combined Endocannabinoid and Cyclooxygenase Inhibition Additively Attenuates Post-Surgical Pain.","authors":"Carl E B Rodriguez, S Olivia Vanegas, A Matthew Reck, Yasmin Schrom, Steven G Kinsey","doi":"10.1089/can.2024.0088","DOIUrl":"10.1089/can.2024.0088","url":null,"abstract":"<p><p><b>Introduction:</b> Post-surgical pain arises following a clinical operation, often persisting throughout recovery. While current treatments reduce pain, repeated use increases the probability of adverse events. monoacylglycerol lipase (MAGL) inhibition has previously been shown to produce analgesia, either through CB<sub>1</sub> or CB<sub>2</sub> mechanisms, dependent on the underlying pain phenotype. Thus, this study investigated the analgesic potential of inhibiting MAGL, alone and in combination with the analgesic non-steroidal anti-inflammatory drug (NSAID) diclofenac sodium in a model of post-surgical pain. <b>Methods:</b> Male and female C57BL/6J mice were subjected to hindpaw incision (HPI) surgery. Mechanical allodynia, climbing, grip strength, and thermal preference were measured 24 h following HPI. The dose-dependent anti-allodynic effects of the MAGL inhibitors (irreversible MAGL inhibitor [JZL184] and selective MAGL inhibitor [MJN110]) and the NSAID diclofenac, as well as the additive potential of combined MAGL and cyclooxygenase (COX) inhibition, were assessed. Selective antagonists of CB<sub>1</sub> and CB<sub>2</sub> receptors were used to challenge the cannabinoid-receptor mechanism of JZL184. Similarly, the anti-allodynic effects of the CB<sub>2</sub>-selective agonist (LY2828360) were tested. JZL184 was administered repeatedly to determine tolerance. Finally, hindpaw cytokines were quantified <i>via</i> multiplex ELISA 24 h after HPI surgery. <b>Results:</b> Approximately 24 h post-surgery, the MAGL inhibitors JZL184 (≥4 mg/kg) or MJN110 (≥5 mg/kg), as well as the NSAID diclofenac sodium (≥16.67 mg/kg), attenuated HPI-induced mechanical allodynia, as assessed with von Frey filaments. The anti-allodynic effects of JZL184 (40 mg/kg) were blocked by pre-treatment of the CB<sub>2</sub> antagonist SR144528 (3 mg/kg) but not the CB<sub>1</sub>-selective antagonist rimonabant (SR141716A; 3 mg/kg), suggesting a CB<sub>2</sub>-mediated mechanism of anti-allodynia <i>via</i> MAGL inhibition. Similarly, LY2828360 (3 mg/kg) reduced HPI-induced allodynia. Moreover, when administered repeatedly, the anti-allodynic effects of JZL184 (8 mg/kg) persisted and did not undergo tolerance. A separate cohort was administered a sub-analgesic dose of JZL184 (1 mg/kg), diclofenac sodium (1.85 mg/kg), or both compounds concurrently. This subthreshold JZL184 and diclofenac sodium combination attenuated HPI-induced allodynia, suggesting an additive drug interaction. Finally, HPI <i>per se</i> increased pro-inflammatory cytokine levels, which were unaltered by MAGL inhibition despite the anti-allodynia assessed behaviorally. <b>Conclusion:</b> These data support simultaneously targeting endocannabinoids and COX enzymes as a potential post-operative pain management approach.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e102-e111"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078662","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 : 2025-02-01 Epub 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":"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":"60-70"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947650/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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