Cannabis and Cannabinoid Research最新文献

{"title":"Sex-Related Differences in Medical Cannabis Use: A Nationwide Database Study.","authors":"Noa Yakirevich Amir, Nir Treves, Eliad Davidson, Inbal Reuveni, Sharon Florentin, Ilan Matok, Omer Bonne","doi":"10.1177/25785125261497797","DOIUrl":"https://doi.org/10.1177/25785125261497797","url":null,"abstract":"<p><strong>Introduction: </strong>With the increasing use of medical cannabis (MC) worldwide, understanding potential sex-related differences in treatment patterns and outcomes has become increasingly important. The objective of this study was to characterize medical cannabis use in Israel, focusing on sex-related differences in usage patterns and adverse effects.</p><p><strong>Methods: </strong>We conducted a population-based, retrospective cohort study using data from the Israeli Medical Cannabis Agency registry (April 2018-March 2022). The dataset includes license holders' demographics, indication for use, monthly dose, THC/CBD concentrations, and reported adverse effects. Sex-related differences were assessed using time-series analyses, Cox models, and relative risk estimates.</p><p><strong>Results: </strong>A total of 135,698 individuals (62% men) were issued a license to use MC in Israel during the study period. Men using MC were significantly younger than women (49 ± 18.3 vs. 55.3 ± 18.1). The leading indications among both sexes were chronic pain, symptoms related to oncological disease and chemotherapy treatment, and post-traumatic stress disorder. At initiation, men received higher monthly quantities than women (29.3 g vs. 26.1 g; <i>p</i> < 0.001), higher THC concentrations (14.3% vs. 11.9%; <i>p</i> < 0.001), and lower CBD concentrations (5.1% vs. 6.5%; <i>p</i> < 0.001). These differences remained significant over 2 years. Men had a lower discontinuation rate (HR 0.95, 95% CI: 0.93-0.97). Women were more likely than men to report at least one adverse effect (RR 1.51, 95% CI: 1.43-1.58).</p><p><strong>Conclusion: </strong>Sex-related differences in MC use likely reflect biological, behavioral, and systemic factors, influencing both outcomes and risk of misuse. These disparities highlight the need for sex-informed clinical approaches and further research to support equitable, evidence-based treatment.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"25785125261497797"},"PeriodicalIF":2.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206578","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":"Prenatal Cannabinoid Exposure Induces Sex-Specific Alterations in Fetal Growth and Placental Lipid Metabolism Gene Expression.","authors":"Rachel West, Adrian Courville, Cristine Camp, Paige Drotos, Carly Parker, Miranda Reed","doi":"10.1177/25785125261497796","DOIUrl":"https://doi.org/10.1177/25785125261497796","url":null,"abstract":"<p><strong>Background: </strong>Prenatal cannabis use is becoming increasingly more commonplace. However, cannabis exposure is linked to adverse pregnancy outcomes, including gestational hypertension, preeclampsia, and preterm birth. The aim of this study was to determine the morphological and molecular effects of prenatal cannabinoid exposure on the placenta.</p><p><strong>Methods: </strong>Pregnant Sprague-Dawley rats were exposed daily to vaporized THC (100 mg/mL) starting at gestational day (GD)5 until GD19, when dams were sacrificed and fetuses and placentas collected. Fetuses were genotyped for genetic sex, and transcriptomic analysis was performed on male and female THC-exposed and control placentas.</p><p><strong>Results: </strong>On GD19, only the female fetuses from the THC group were significantly larger than those of the control, with no significant differences in placental weights or fetal:placental weight ratios. RNA sequencing revealed enriched biological processes related to nutrient transport and lipid catabolism, protein-lipid complex formation, and lipoprotein particle remodeling and organization. Further transcriptomic analysis determined that the differentially expressed genes and enriched biological processes related to lipid metabolism were preferentially enriched in the female THC placentas compared to the male, suggesting a sex-specific effect.</p><p><strong>Discussion: </strong>Collectively, these data present sex-specific effects of prenatal cannabinoid exposure on placental growth and global gene expression. These data also suggest that sex influences gene expression of genes related to lipid metabolism in the THC-exposed placentas.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"25785125261497796"},"PeriodicalIF":2.5,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164686","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":"Impact of Cannabis (Marijuana) on Nicotine Metabolism in U.S. Adults Who Smoke Cigarettes: Findings from NHANES 2013-2018.","authors":"Wanyu Hua, Philip Lazarus, Tolulope V Adebile, Joshua E Muscat","doi":"10.1177/25785125261493188","DOIUrl":"https://doi.org/10.1177/25785125261493188","url":null,"abstract":"<p><strong>Background: </strong>A pharmacologic approach for smoking cessation is enzyme inhibition. Cytochrome P450 2A6 (CYP2A6)-mediated nicotine metabolism is a key target, yet no safe or effective inhibitors are currently available. We examined associations between marijuana use and the nicotine metabolite ratio (NMR) in adults who smoke.</p><p><strong>Methods: </strong>We conducted a cross-sectional analysis of adults who currently smoke in the National Health and Nutrition Examination Survey (NHANES) 2013-2018. Marijuana use was assessed by two self-reported measures: marijuana use every month for 1 or more years and frequency of marijuana use. NMR was calculated as the ratio of serum <i>trans</i>-3'-hydroxycotinine (3-HCOT) to cotinine and categorized into quartiles based on weighted population cutoffs. Survey-weighted multinomial models adjusted for sociodemographic covariates were used.</p><p><strong>Results: </strong>Among 2984 adults who currently smoke, marijuana use every month for 1 or more years was associated with lower NMR. Compared with those who didn't use marijuana, participants who used marijuana every month for 1 or more years had reduced odds of being in NMR quartile 4 (adjusted odds ratio [aOR] = 0.59, 95% confidence interval [CI] = 0.41-0.85); no significant association was observed for quartile 2 or 3. When the frequency of marijuana use (DUQ230) was modeled categorically, weekly users had reduced odds of quartile 4 classification relative to never users (aOR = 0.53, 95% CI = 0.31-0.91). Monthly and daily use frequency showed a similar direction of association with reduced odds of quartile 4 classification (aOR = 0.73, 95% CI = 0.37-1.44; and aOR = 0.54, 95% CI = 0.28-1.04, respectively), though these did not reach statistical significance.</p><p><strong>Conclusions: </strong>People who smoke cigarettes and co-use marijuana had a lower NMR. Pharmacokinetic studies are needed to further determine whether cannabinoids affect nicotine metabolism.</p><p><strong>Impact: </strong>The nonpsychoactive forms of cannabinoids may be useful for the treatment of tobacco use disorder.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"25785125261493188"},"PeriodicalIF":2.5,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163988","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":"Awareness and Use of Delta-8-THC Cannabis Products in the United States: Findings from National Surveys in 2021 and 2022.","authors":"Gillian Schauer, Maryam Iraniparast, David Hammond","doi":"10.1177/25785125261492385","DOIUrl":"https://doi.org/10.1177/25785125261492385","url":null,"abstract":"<p><strong>Introduction: </strong>While recreational marijuana remains illegal under federal law in the United States, \"hemp-derived\" products that contain less than ≤ 0.3% Delta-9-tetrahydrocannabinol (THC) were legalized in 2018. New classes of intoxicating products have proliferated, such as Delta-8 products, with few regulatory restrictions. The current study sought to assess awareness and prevalence of use of Delta-8-THC products in the United States.</p><p><strong>Materials and methods: </strong>Data are from 69,564 U.S. 16-65-year-old respondents to the 2021-2022 International Cannabis Policy Study (ICPS). Participants were asked about awareness, ever use, and past-month use of specific THC isomers. Logistic regression models examined correlates in the awareness and use of Delta-8-THC, including state cannabis laws.</p><p><strong>Results: </strong>In 2021, 14.5% of respondents reported 'hearing' about Delta-8 products, which increased to 21.8% in 2022 (AOR = 1.76, 95% CI = 1.59-1.95, <i>p</i> < 0.001). Ever use of Delta-8 was higher in states where 'conventional' Delta-9 cannabis was illegal (11.2%), compared with states where medical cannabis (8.5% vs. 11.2%, AOR = 0.68, 95% CI = 0.58-0.79, <i>p</i> < 0.001) and adult-use recreational cannabis is legal (6.5% vs. 11.2%, AOR = 0.44, 95% CI = 0.36-0.55, <i>p</i> < 0.001).</p><p><strong>Discussion: </strong>The cannabinoid market is rapidly diversifying with increased use of hemp-derived cannabinoid products, particularly in states where Delta-9-THC cannabis remains illegal.</p><p><strong>Conclusions: </strong>There is an urgent need for enhanced monitoring of the diversifying cannabinoid market. Education is warranted to inform consumers about the type and potential health risks of novel hemp-derived products.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"25785125261492385"},"PeriodicalIF":2.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126591","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":"Advancing a Pre-Clinical Model of Full-Term Prenatal Exposure to Vaporized Δ9-Tetrahydrocannabinol.","authors":"Bryan W Jenkins, Catherine F Moore, Praachi Tiwari, Aron H Lichtman, Justin L Poklis, Lauren L Jantzie, Elise M Weerts","doi":"10.1177/25785125261493191","DOIUrl":"https://doi.org/10.1177/25785125261493191","url":null,"abstract":"<p><strong>Introduction: </strong>Use of cannabinoid vape products during pregnancy is a major public health concern. <math><mo>Δ</mo></math>9-tetrahydrocannabinol (THC), the main psychoactive constituent in cannabis, is rapidly absorbed after inhalation and transferred to the fetal brain. We developed a novel model of prenatal cannabinoid exposure (PCE) comprising THC vapor exposure across the human-equivalent full-term prenatal period in rats. This study examined gestational/parturitional outcomes and the distribution and metabolism of THC in maternal and filial blood and brains using this model.</p><p><strong>Materials and methods: </strong>Pregnant female Sprague-Dawley rats were exposed to THC (200 mg/mL, <i>n</i> = 13) or vehicle (100% propylene glycol, <i>n</i> = 8) vapor daily during gestation until postnatal day (PD) 10 (i.e., human-equivalent full-term). Pups were exposed directly in the postnatal period. Gestational/parturitional assessments included dam food intake, dam and pup body weights, total gestation days, litter size, and sex ratio. Subsets of THC-exposed dams and pups were sampled immediately postvapor on gestational day (GD) 20 (<i>n</i> = 4 dams, 24 pups) or PD 10 (<i>n</i> = 2 dams, 33 pups) to quantify THC and its metabolites (11-hydroxy-Δ9-tetrahydrocannabinol [11-OH-THC], and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol [THCCOOH]) concentrations in the brain (dams and pups) and plasma (dams).</p><p><strong>Results: </strong>THC decreased dam food intake and total gestation days compared to controls. THC concentrations in dam plasma and brain were 14.8 ± 47.8 ng/mL and 80.5 ± 38.6 ng/g on GD 20 and 68.9 ± 25.0 ng/mL and 125.0 ± 4.2 ng/g on PD 10. Birth weights were not different between THC-exposed offspring and controls, but postnatal weights were decreased. On GD 20, fetal brain THC, 11-OH-THC, and THCCOOH concentrations were 12 ± 5%, 118 ± 7%, and 75 ± 34% of maternal plasma. On PD 10, pup brain THC and 11-OH-THC concentrations were 29.6 ± 8.5 and 9.8 ± 2.1 ng/g. THCCOOH was not detected in PD 10 pup brain.</p><p><strong>Discussion: </strong>THC readily transferred from dams to pup brains during gestation in our full-term vapor exposure model. High THC and 11-OH-THC concentrations were detected in pup brains at both timepoints. This novel model is a valuable tool to investigate long-term effects of full-term PCE on offspring brain development and behavior.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"25785125261493191"},"PeriodicalIF":2.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126608","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":"Pharmacokinetic Differences Between Fast-Acting, Standard, and Placebo Cannabis Edibles.","authors":"Bradley T Conner, Emma E Smith, Samuel M DiCecco, Kira L Sturgess, Hollis C Karoly, Gregory Dooley, Natalie Akagi, Charles Villanueva, Michael Hennesy","doi":"10.1177/25785125261441366","DOIUrl":"10.1177/25785125261441366","url":null,"abstract":"<p><strong>Introduction: </strong>Edibles have become the second-most used cannabis product in legal U.S. states, wherein 64% of cannabis consumers reported using edibles within the past year. Among expansions to the legal cannabis industry are the newly marketed \"fast-acting\" edible compounds, which may address many of the issues associated with edible use related to overdose and dose management. The study hypotheses were that fast-acting edibles would reach peak concentration significantly faster than standard edibles and placebo edibles.</p><p><strong>Materials and methods: </strong>Twenty participants completed three arms within-subjects designed study to test hypotheses. The three arms were ingestion of a (1) fast-acting edible, (2) a standard edible, and (3) a Δ9-tetrahydrocannabinol (THC) terpene-derived placebo edible that was indistinguishable from the two THC-containing edibles. Blood plasma was analyzed for the presence of THC and THC analytes. The pharmacokinetic parameters tested were time to max concentration (Tmax), maximum concentration (Cmax), terminal half-life (t_1/2), and area under the curve (AUC).</p><p><strong>Results: </strong>Results supported study hypotheses in that Tmax was significantly faster for the fast-acting edible, observed 30 min post-ingestion and, on average, 30 min earlier than the Tmax for the standard edible. There were no significant differences between the fast-acting and standard edibles on Cmax, t_1/2, and AUC; however, both the fast-acting and standard edibles were significantly different compared with the placebo across all pharmacokinetic parameters.</p><p><strong>Discussion: </strong>The results indicate that the microencapsulation technology used to create the fast-acting edible enabled analyte concentrations to peak significantly faster compared to the standard and placebo edibles.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"385-395"},"PeriodicalIF":2.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644243","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":"Emerging Hemp-Derived Semi-Synthetic Cannabinoids, Absent Regulations: Patterns of Use and Adverse Effects Among a Sample of U.S. Cannabis Consumers.","authors":"Elisa Pabon, Stephanie Lake, Conor H Murray, Ziva D Cooper","doi":"10.1177/25785125251391987","DOIUrl":"10.1177/25785125251391987","url":null,"abstract":"<p><strong>Introduction: </strong>Hemp-derived semi-synthetic cannabinoids are marketed as legal alternatives to cannabis containing ≥0.3% Δ⁹-tetrahydrocannabinol (THC) but remain unregulated at the federal and state levels. Their growing availability underscores the urgent need to investigate patterns of use and associated health risks.</p><p><strong>Methods: </strong>Data were collected <i>via</i> an online survey on self-reported patterns and associations of semi-synthetic cannabinoid use, as well as related factors and effects, from a sample of U.S. adults (≥18 years old) who reported past-year cannabis use.</p><p><strong>Results: </strong>In the sample (<i>N</i> = 229; 55.5% male, 63.8% White, 80.3% not Hispanic/Latino), nearly half (44.5%) reported using at least one semi-synthetic cannabinoid in the past year. Patterns of use varied by cannabinoid: Δ⁷-THC (10.0%), Δ⁸-THC (21.8%), Δ¹⁰-THC (14.0%), THC-O-acetate (5.2%), THC homologue tetrahydrocannabiphorol (24.4%), and hydrogenated derivative hexahydrocannabinol (3.5%). Older individuals had lower odds of reporting past-year semi-synthetic cannabinoid use (adjusted odds ratio [aOR] = 0.96, 95% confidence interval [CI] = 0.94, 0.99, <i>p</i> = 0.004); factors associated with higher odds of reporting semi-synthetic cannabinoid use included reporting 101-1,000 lifetime cannabis uses (vs. <100 times; aOR = 2.55, 95% CI = 1.02, 6.38, <i>p</i> = 0.046), reporting 1,001-10,000 lifetime cannabis uses (vs. <100 times; aOR = 4.40, 95% CI = 1.57, 12.33, <i>p</i> = 0.005), and reporting non-inhaled forms of cannabis as the most frequent route of administration in the past year (vs. smoking; aOR = 2.98, 95% CI = 1.18, 7.53, <i>p</i> = 0.021). Adverse effects were reported across all semi-synthetic cannabinoids.</p><p><strong>Discussion: </strong>Semi-synthetic cannabinoid use was prevalent among this sample, especially among younger individuals. Despite their popularity, adverse effects underscore the need for regulation and research to address these products' safety and public health implications.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"396-404"},"PeriodicalIF":2.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667275","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":"Using Chemical Ecology as a Guide for Development and Differentiation of Clinically Relevant Phytochemical Profiles in Cannabis Trichome.","authors":"Michael Tims, John Courie, Joseph M Betz","doi":"10.1177/25785125251391985","DOIUrl":"10.1177/25785125251391985","url":null,"abstract":"<p><p>This article examines the effects of biotic and abiotic influences on trichome development in cannabis and how these influences may shape the ultimate cannabinoid and terpene profiles in cannabis cultivars. As cannabis agriculture focuses primarily on either high tetrahydrocannabinol or cannabidiol production, the result has been an attenuation of genetic and chemical diversity observed in contemporary cannabis cultivars. Techniques for modulating trichome development remain an active area of commercial importance. The clinically therapeutic role of varied cannabis metabolite profiles, which include the wider range of cannabinoids and terpenes, also ultimately tied to trichome development. This review will analyze how different stressors can modify phytochemical ratios and alter trichome development.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"357-376"},"PeriodicalIF":2.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809515","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":"Evaluating the Association of Cannabis Use and Longitudinal Kidney Outcomes.","authors":"Flor Alvarado, Dingfen Han, Alan B Zonderman, Michele K Evans, Deidra C Crews","doi":"10.1177/25785125251363813","DOIUrl":"10.1177/25785125251363813","url":null,"abstract":"<p><strong>Background: </strong>Cannabis is the most used federally controlled substance in the United States. Given the increasingly widespread use of cannabis, further examination of its health implications is needed. We evaluated the association of cannabis use and longitudinal kidney outcomes among a cohort of adults living in Baltimore, MD.</p><p><strong>Methods: </strong>We used data from healthy aging in neighborhoods of diversity across the life span study. Baseline cannabis use (obtained between 2004 and 2009) was categorized as never tried, tried, never used regularly (irregular use), regular use >6 months prior (former regular use), and regular use within the past 6 months (current regular use). The primary outcome was incident chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² at follow-up (2013-2017). Risk of rapid kidney function decline (decline in eGFR of >3 mL/min per 1.73 m² per year) and incident albuminuria (albumin-to-creatinine ratio [ACR] ≥ 30 mg/g) were also assessed. Multivariable logistic regression was used to evaluate the association of cannabis use with kidney outcomes.</p><p><strong>Results: </strong>Among 1,521 participants, the mean age was 48 years, 58% were female, and 58% were of Black race. Participants with current regular cannabis use were more likely to be younger, male, Black, and to concurrently use cigarettes, opiates, and/or cocaine. Compared with those with no history of cannabis use, participants with current regular cannabis use were not at higher risk of incident CKD (OR: 0.79 [95% CI: 0.37-1.68]), rapid kidney function decline (OR: 0.80 [95% CI: 0.43-1.49), or incident albuminuria (OR: 0.84 [95% CI: 0.38-1.87]) after adjustment for sociodemographics, health factors, and concurrent use of cigarette, opiate, or cocaine.</p><p><strong>Conclusion: </strong>In this Baltimore-based cohort of adults without CKD, there was no independent association between cannabis use and adverse kidney outcomes over time.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"377-384"},"PeriodicalIF":2.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741276","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":"Monoacylglycerol Lipase Inhibition by JZL184 Improves Neurological Outcomes and Survival after Cardiac Arrest via 2-AG-Mediated Restoration of Cerebral Microcirculation.","authors":"Nan Gu, Xu Ma, Wanrong Wang, Tongjie Pan, Xue Cao, Li Shen, Chenhui Ma, Wenxun Liu, Yong Yang, Shaozhang Hou, Kerong Hai","doi":"10.1177/25785125261490165","DOIUrl":"https://doi.org/10.1177/25785125261490165","url":null,"abstract":"<p><strong>Background: </strong>Improving long-term survival rates after cardiac arrest (CA) is an important clinical challenge. The endocannabinoid 2-arachidonoylglycerol (2-AG) exerts endogenous neuroprotective and anti-inflammatory effects; its hydrolysis by monoacylglycerol lipase (MAGL) not only terminates 2-AG signaling but also releases arachidonic acid (AA), a precursor to multiple proinflammatory mediators. We hypothesized that inhibiting MAGL with JZL184 would improve neurological outcomes after CA by increasing the levels of 2-AG and suppressing AA-induced inflammation.</p><p><strong>Methods: </strong>In a clinical cohort, we assess the correlations between plasma endocannabinoid levels and the neurological outcomes of CA patients at 7 days postresuscitation. In rat models of asphyxia-induced CA, the animals were randomly allocated to the Sham, cardiopulmonary resuscitation (CPR), or CPR + JZL184 (16 mg/kg, intraperitoneal) groups. Within 7 days after the return of spontaneous circulation (ROSC), we assessed survival, neurological deficit scores (NDSs), spatial memory, cerebral edema, cerebral blood volume (CBV) (<i>via</i> functional ultrasound), and the levels of key lipid mediators (2-AG, AEA, AA, TXB2, and PGs) in the brain.</p><p><strong>Results: </strong>A favorable outcome was associated with higher 2-AG levels at 6 h and lower AA levels at 1 and 5 days after ROSC among the patients (<i>p</i> < 0.05). In rats, JZL184 treatment significantly increased the 7-day survival rate, improved NDSs and memory function, attenuated cerebral edema, and promoted cerebral microcirculatory recovery (CBV, <i>p</i> < 0.01). Mechanistically, JZL184 robustly increased cerebral 2-AG levels while reducing the levels of AA and its proinflammatory metabolites (TXB2 and PGs, <i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>The MAGL inhibitor JZL184 confers substantial neuroprotection after CA and CPR by modulating the lipid mediator network in the brain. It alleviates cerebral injury and improves survival and neurological recovery primarily by increasing the levels of 2-AG and concurrently suppressing the AA-induced inflammatory cascade.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"25785125261490165"},"PeriodicalIF":2.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058540","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}