Journal of cannabis research最新文献

{"title":"Who is at risk? Core mental health symptoms and problematic cannabis use in Germany.","authors":"Eva-Maria Krowartz, Larissa Schwarzkopf, Sally Olderbak, Stefanie J Klug, Gabriele Koller, Esther Neumeier, Elena Gomes de Matos, Eva Hoch","doi":"10.1186/s42238-026-00430-y","DOIUrl":"10.1186/s42238-026-00430-y","url":null,"abstract":"<p><strong>Background and aims: </strong>Cannabis is one of the most used psychoactive substances worldwide. This study presents nationally representative data on core mental health symptoms and other characteristics among individuals in Germany who used cannabis in the past 12 months, stratified into those with and without problematic cannabis use.</p><p><strong>Methods: </strong>Data were drawn from the 10th wave (2021) of the Epidemiological Survey of Substance Abuse, a cross-sectional survey of adults aged 18-64 years living in private households in Germany. The analytic sample included 1,004 past-year cannabis users. Problematic cannabis use was assessed using the Severity of Dependence Scale with sex-specific cut-offs (≥ 2 for women, ≥ 4 for men). Core mental health symptoms were measured with the DIA-X-Core Screening Questionnaire and categorized into 0, 1-3, or ≥ 4 symptoms. Analyses were weighted to match the German population. Descriptive comparisons between individuals with and without problematic use employed χ²-tests. Multivariable logistic regression models examined associations between problematic use and cumulative symptom scores, adjusting for covariates. P-values were corrected using the Simes-Benjamini-Hochberg procedure.</p><p><strong>Findings: </strong>Among individuals with past-year cannabis use, 25.0% met criteria for problematic use. Compared with those without problematic use, these individuals were more likely to have a low educational level (27.2% vs. 10.8%), use cannabis weekly or almost daily (66.8% vs. 14.8%), begin use before age 15 (40.8% vs. 19.1%), currently use tobacco (73.1% vs. 49.7%), and report problematic amphetamine- (10.5% vs. 2.2%) and tobacco use (23.8% vs.14.0%). They were less likely to report no core mental health symptoms (12.7% vs. 25.3%) and more likely to report ≥ 4 symptoms (40.8% vs. 27.2%). Adjusted models showed that reporting ≥ 4 symptoms was positively associated with problematic use (aOR = 1.68; 95% CI [1.12-2.53]; p=.027), whereas having no symptoms was associated negatively (aOR = 0.41; 95% CI [0.23-0.73]; p=.006).</p><p><strong>Conclusion: </strong>Amid changing cannabis laws in Germany, this study identifies risk factors for problematic use and highlights that core mental health symptoms are associated with problematic cannabis use. The findings underscore the importance of early screening and targeted prevention strategies.</p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":"8 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13237940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148166352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of THC-containing cannabis for inflammatory bowel disease: a systematic review.","authors":"Sebastian Jugl, Silvia Perez-Vilar, Steven Galati, Sukhminder K Sandhu, Hung-Kai Chen, Shao-Hsuan Chang, Yehua Wang, Thorben Kurzbach, Lauren Adkins, Jingchuan Guo, Yan Wang, Almut G Winterstein, Amie Goodin","doi":"10.1186/s42238-026-00456-2","DOIUrl":"10.1186/s42238-026-00456-2","url":null,"abstract":"<p><strong>Background: </strong>Patients with inflammatory bowel disease (IBD) increasingly use cannabis. Studies investigating the effectiveness and safety of cannabis as a therapeutic option for IBD have reported conflicting findings, and recent reviews have not incorporated evidence from real-world studies. This systematic review assessed controlled non-interventional studies and interventional trials evaluating the effectiveness of delta-9-tetrahydrocannabinol (THC)-containing cannabis products in patients with IBD.</p><p><strong>Methods: </strong>The systematic review procedures-including search strategy across four databases, literature screening, data extraction, qualitative result synthesis, and risk of bias assessment-followed the Cochrane Handbook and adhered to PRISMA-compliant reporting. We used the GRADE approach to rate evidence quality for each outcome.</p><p><strong>Inclusion criteria: </strong>peer-reviewed research on effectiveness or safety of cannabis as treatment modality, control group must be present, quantitative measure of effect/safety on IBD.</p><p><strong>Exclusion criteria: </strong>published before 2000, non-English, non-human research, non-cannabis/THC exposures, < 0.3% THC exposure, topical formulations.</p><p><strong>Results: </strong>Four randomized clinical trials (RCTs), and four non-interventional studies met all inclusion criteria. Non-interventional studies exhibited serious or critical risk of bias, leading to their exclusion from evidence ratings. The four RCTs demonstrated high risk of bias, although their evidence quality ratings varied. RCTs assessed adverse events; however, limited safety information was provided. Improvements in one trial were reported for bloating (n = 56) and appetite (n = 56), both rated as low evidence quality. Results for clinical disease activity scores (4 trials, n = 180), daily function, general well-being, general effect on health (1 trial, n = 56), bowel movement frequency (3 trials, n = 148), generic quality of life (3 trials, n = 122) and pain (2 trials, n = 88) were mixed. The outcomes of remission (3 trials, n = 150), weight (1 trial, n = 56), IBDQ (1 trial, n = 60), endoscopic scores (2 trials, n = 88), and nausea (1 trial, n = 56), consistently failed to differ meaningfully between intervention and control. The evidence quality rating for these null or inconclusive results varied from low to medium, with the exception of weight, rated as high, though no effect was reported.</p><p><strong>Conclusions: </strong>Current evidence is inconclusive as to whether THC-containing cannabis products might have a positive effect in IBD, given heterogenous findings and mostly low-to-moderate evidence quality. Higher quality cannabis research is needed given widespread utilization.</p><p><strong>Trial registration: </strong>PROSPERO: CRD42023411910.</p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148152942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy, effectiveness and safety of medical cannabis in PTSD: a scoping review.","authors":"Joshua Aviram, Rostislav Belobrov, Shulamit Grinapol, Eyal Fruchter","doi":"10.1186/s42238-026-00451-7","DOIUrl":"10.1186/s42238-026-00451-7","url":null,"abstract":"<p><strong>Background: </strong>Although current treatment guidelines recommend against cannabinoids for Post-Traumatic Stress Disorder (PTSD), their use has increased in clinical settings despite fragmented evidence. This review critically examines the efficacy, effectiveness, and safety of cannabinoid-based interventions for PTSD.</p><p><strong>Methods: </strong>We conducted a scoping review following PRISMA-ScR guidelines. Five databases were searched up to December 22, 2024. Eligible studies included randomized controlled trials (RCTs) and observational studies, investigating cannabinoids in PTSD-diagnosed populations. Screening, extraction, and quality appraisal independently performed. Quality assessed using validated tools. Main outcomes included PTSD symptom severity and adverse events (AEs).</p><p><strong>Results: </strong>From 1,474 screened titles, 26 studies included: 7 RCTs, 9 prospective, 9 retrospective observational studies, and one unpublished RCT, totaling 3,598 patients. Among the seven RCTs, only one demonstrated a statistically significant reduction in PTSD-related nightmares (nabilone vs. placebo). Two RCTs using inhaled or oral cannabis did not show superiority over placebo. Two additional RCTs evaluating oral THC during fear extinction tasks identified changes in neurobiological activation (e.g., increased ventromedial prefrontal cortex activity or reduced fear renewal) without clinical symptom improvement. The remaining two RCTs involving acute oral CBD administration showed minimal benefit, limited to transient mood or cognitive modulation during trauma recall. Overall, only one of the seven RCTs showed clear clinical efficacy over placebo; the rest showed no significant group differences. Observational studies frequently reported symptom improvements, particularly in nightmares, hyperarousal, sleep, and quality of life; however, these findings are limited by high risk of bias, reliance on self-reported outcomes, and lack of control groups, reducing confidence in causal interpretations. AEs were generally mild (e.g., dry mouth, dizziness). Risk of bias was high in most observational studies and moderate in RCTs.</p><p><strong>Conclusions: </strong>The current evidence from high-quality RCTs remains insufficient to support clinical use of cannabinoids in treating PTSD. The therapeutic role of cannabinoids in PTSD should be further evaluated through rigorous RCTs.</p><p><strong>Trial registration: </strong>The review design was developed 'a priori' to data collection initiation but was not registered in PROSPERO prior to initiation.</p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13425960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148059398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knowledge, attitudes, and concerns about medical cannabis among U.S. healthcare professionals.","authors":"Lakshmi Kumar, Erin Wang, David S Mathai, C Austin Zamarripa, Tory R Spindle, Ryan Vandrey, Albert Garcia-Romeu","doi":"10.1186/s42238-026-00450-8","DOIUrl":"10.1186/s42238-026-00450-8","url":null,"abstract":"<p><strong>Background: </strong>Cannabis is among the most widely consumed psychoactive substances, with increasing consumption due to growing legalization for medical and non-medical use. As access expands, healthcare providers are faced with clinical challenges, despite variability in knowledge and attitudes on cannabis use in clinical practice.</p><p><strong>Methods: </strong>We conducted an anonymous, cross-sectional web-based survey of U.S. healthcare professionals to assess knowledge and attitudes regarding cannabis use in clinical settings. Participants completed demographic items, self-report measures of cannabis-related beliefs and attitudes, and an objective knowledge assessment covering cannabis therapeutic indications, risks, and mechanisms of action. Descriptive analyses were conducted, followed by multivariable linear regression models examining whether demographic characteristics, knowledge, or concerns predicted openness to the clinical use of cannabis.</p><p><strong>Results: </strong>Among 879 respondents (71% female; 86% White; mean age = 46 years), 89% reported having patients who use cannabis. The sample included mental health professionals (29%), registered nurses (25%), physicians (18%), and advanced practice providers (15%). Participants rated their self-reported knowledge highest for cannabis's risks (mean = 4.1/5), followed by therapeutic indications (mean = 4.0/5), and mechanisms of action (mean = 3.5/5). In contrast, objective knowledge check scores were generally low across these domains (13-64% correct). Personal experience (76%) and popular media (73%) were the most endorsed sources of cannabis-related knowledge. Overall, most respondents (87%) endorsed the therapeutic promise of cannabis, 74% reported openness to recommending medical cannabis, and 95% supported its legal medical use. Commonly cited concerns regarding clinical use of cannabis included lack of trained providers (35%), possible patient exploitation (22%), recreational misuse (21%), and risk of psychosis (20%). Greater openness to clinical use was associated with higher self-rated knowledge, younger age, professional role, and lower levels of concern.</p><p><strong>Conclusions: </strong>Although most respondents reported having patients who use cannabis and were largely supportive of medical cannabis use, objective knowledge gaps and limited formal training were evident. These findings suggest a need for structured clinical training on cannabis pharmacology, dosing, contraindications, and legal and ethical frameworks, as well as better monitoring of cannabis use to support safe and informed patient care.</p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13425986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148059350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solubility-improved and antitumor activity of (-)-cannabidiol conjugates.","authors":"Daniel Crespo, Javier Moreno, Cristina Mesas, Amelia Díaz, Iván Cheng-Sánchez, Francisco Sarabia, J Manuel López-Romero, Consolación Melguizo, José Prados","doi":"10.1186/s42238-026-00453-5","DOIUrl":"10.1186/s42238-026-00453-5","url":null,"abstract":"<p><strong>Background: </strong>(-)-Cannabidiol (CBD) is a naturally occurring terpenoid belonging to the cannabinoid family, which is isolated from the Cannabis sativa L. plant. It possesses significant therapeutic potential, providing minimal side effects and no psychoactive activity. However, CBD applications are limited by a poor aqueous solubility and low bioavailability.</p><p><strong>Objective: </strong>To address these limitations and investigate the impact of structural modification on solubility, we plan in this work the synthesis of a series of CBD conjugates along with the evaluation of their antitumor activity.</p><p><strong>Methods: </strong>Conjugates are characterized by Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) techniques, along with the solubility in water, glycerine, n-hexane and isooctane evaluated by High-Performance Liquid Chromatography (HPLC). The antitumoral activity of the CBD conjugates has been tested using cytotoxicity (IC₅₀), cell migration and cell colony formation assays against lung adenocarcinoma cells A549.</p><p><strong>Results: </strong>Specifically, oligo(ethylene glycol)-, alkyl- and L-valine-functionalized CBD derivatives are synthesized via selective esterification of its phenolic groups in good yields. Solubility profiles revealed a marked improvement compared to CBD. Notably, oligo(ethylene glycol) derivatives significantly enhanced solubility in water and glycerine, with 1b exhibiting a 14-fold increase in water solubility. The L-valine bis-conjugated derivative 4 also exhibited substantially improved solubility across all tested solvents, reaching up to a 13-fold increase in glycerine. In contrast, alkyl conjugates 2a,b showed only modest improvements. In addition, the in vitro evaluation against A549 revealed improved cytotoxic activity for 1a, 1b and 4 compared to native CBD, and with 1a additionally displaying antimigratory and colony formation inhibitory effects.</p><p><strong>Conclusions: </strong>Collectively, our results highlight the critical role of conjugate structure in modulating physicochemical and biological properties of CBD and underscore the potential of these CBD conjugates as promising candidates for further pharmacological investigation and development.</p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13450066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148059353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary: Methodological considerations in the interpretation of evidence on cannabis-based medicines for chronic neuropathic pain.","authors":"Wellington Briques, Débora Maria Russiano Pereira, Aderbal Silva Aguiar Junior","doi":"10.1186/s42238-026-00448-2","DOIUrl":"10.1186/s42238-026-00448-2","url":null,"abstract":"<p><p>Recent systematic reviews, including a Cochrane review, have concluded that the certainty of evidence supporting the use of cannabis-based medicines for chronic neuropathic pain remains low. While this overall conclusion is reasonable, its interpretation warrants careful scrutiny. In this commentary, key methodological and interpretative aspects relevant to the appraisal of this evidence base are examined, with particular attention to the application of the GRADE framework, clinical heterogeneity, outcome selection, and indirectness. It is proposed that inconsistent or insufficiently transparent application of methodological criteria may influence how results are interpreted and communicated, with potential implications for clinical decision-making. A cautious, consistent, and context-aware interpretation of the available evidence is essential to avoid both overstatement and undue dismissal of therapeutic effects in a complex and heterogeneous condition such as neuropathic pain.</p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":"8 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148045355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adolescent with cannabis use disorder and other mental health disorders: does dual disorder worsen school impairment?","authors":"J L Matali, E Flores, X Estrada-Prat, A Bonillo","doi":"10.1186/s42238-026-00449-1","DOIUrl":"10.1186/s42238-026-00449-1","url":null,"abstract":"<p><strong>Introduction: </strong>Despite evidence of the impact on academic performance of cannabis use disorder (CUD) there is little information about what happens in those cases of dual diagnosis, when CUD occurs along with other mental health disorders (DD).</p><p><strong>Methods: </strong>Participants in this study (N = 300) were recruited from patients seeking treatment for CUD at an adolescent addictive behaviors unit. A multivariate logistic regression analysis was conducted to evaluate the effects of DD on school impairment (listwise deletion strategy). The interaction between CUD and other mental health disorders was included, along with covariates such as age of onset, years elapsed from first use to problematic use, and sex.</p><p><strong>Results: </strong>The presence of co-occurring internalizing and/or externalizing disorders among adolescents with CUD was associated with higher odds of school impairment (OR = 3.73; 95% CI: 1.06-13.12; p = .04). In the adjusted model, psychiatric comorbidity was also associated with approximately twice the likelihood of repeating a grade or dropping out of school (OR = 2.05; 95% CI: 1.10-3.84; p = .03), whereas the CUD-only group, sex, age of initiation, and latency to regular cannabis use were not statistically significant predictors. These findings suggest that school impairment is particularly associated with the co-occurrence of CUD and other mental health disorders.</p><p><strong>Conclusions: </strong>DD in adolescents emerges as a risk factor for academic performance. It is crucial to develop early intervention policies and approaches that comprehensively address DD.</p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148019931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Operationalizing ASSIST-based indicators to estimate the prevalence and correlates of problematic cannabis involvement among U.S. college students.","authors":"Fares Qeadan, Ashlie McCunn, Anumitha Aravindan, Benjamin Tingey","doi":"10.1186/s42238-026-00446-4","DOIUrl":"10.1186/s42238-026-00446-4","url":null,"abstract":"<p><strong>Background: </strong>Cannabis use and cannabis-related harms remain important public health concerns among college-age adults. However, nationally representative estimates that characterize the severity of problematic cannabis use in U.S. college students are limited. Using pooled American College Health Association-National College Health Assessment (ACHA-NCHA) III data, we developed a screening-based index of cannabis involvement severity and examined mental health and other correlates.</p><p><strong>Methods: </strong>This cross-sectional study used pooled ACHA-NCHA III data from Fall 2019 to Spring 2024. Cannabis involvement severity was operationalized using cannabis-specific items from the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) module embedded in the ACHA-NCHA III (e.g., use frequency, craving/urge, difficulty controlling use, role impairment, and cannabis-related problems). Indicator responses were summed and categorized as no/low involvement (0-1), mild (2-3), moderate (4-5), or severe/high involvement (≥ 6). We estimated prevalence overall and among students with lifetime cannabis use. Ordinal logistic regression identified correlates of greater involvement severity among those with lifetime cannabis use. Modified Poisson and log-linear models assessed associations between involvement severity and mental health indicators among students with cannabis use history.</p><p><strong>Results: </strong>The prevalence of elevated problematic cannabis involvement (score ≥ 2) was 8.66% among all students and 20.77% among those with lifetime cannabis use; among students with cannabis use history, 7.32% had mild involvement, 6.88% moderate involvement, and 6.56% severe/high involvement. Greater involvement severity was more common among males, American Indian/Alaskan Native/Non-Hispanic (NH) Black/NH Other/NH multiracial students (compared with NH White), undergraduates (compared with Master's/PhD students), and those not living on campus, and was associated with greater co-occurring tobacco/other substance use and greater counts of chronic mental health conditions. Compared to students with no/low cannabis involvement, those with mild/moderate/severe involvement had higher prevalence of anxiety, depression, other mental health conditions, and mental health service receipt, as well as higher non-specific serious mental illness, loneliness, and suicide behavior scores.</p><p><strong>Conclusions: </strong>Problematic cannabis involvement is common among U.S. college students and shows a graded association with adverse mental health indicators. These findings support targeted screening and integrated behavioral health services for students reporting more severe patterns of cannabis involvement.</p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13339261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147936781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative network analysis reveals organizational principles of the endocannabinoid system.","authors":"Aanya Shridhar, Sugyan Mani Dixit, Anthony Torres, Reggie Gaudino","doi":"10.1186/s42238-026-00447-3","DOIUrl":"10.1186/s42238-026-00447-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The endocannabinoid system (ECS) is a complex signaling network that regulates diverse physiological processes, including pain, mood, metabolism, and immune response, through coordinated interactions among receptors, enzymes, and lipid-derived ligands. Although individual ECS components have been extensively studied, the integrated systems-level organization and structural dependencies of the ECS remain insufficiently characterized in a unified network context. Here, we present a computational, network-based systems analysis of the ECS that integrates protein-protein and protein-chemical interactions into a unified interaction framework, enabling the identification of components that occupy structurally prominent positions in the network, with potential relevance to the role of ECS in diverse physiological processes and therapeutic contexts.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We constructed integrated ECS networks by combining experimentally validated protein-protein and protein-chemical interactions from multiple public databases. Network analyses were performed using centrality metrics, community detection algorithms, and targeted perturbations of highly ranked nodes to assess structural organization, modular architecture, and redistribution of topological influence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Centrality analyses systematically identified nodes with high topological prominence across the ECS network. Canonical receptors cannabinoid receptor 1 (CB&lt;sub&gt;1&lt;/sub&gt;) and cannabinoid receptor 2 (CB&lt;sub&gt;2&lt;/sub&gt;) ranked consistently among the most influential nodes, while non-canonical components such as transient receptor potential vanilloid 1 (TRPV1), G-protein coupled receptor 55 (GPR55), peroxisome proliferator-activated receptor alpha (PPARα), cyclooxygenase-2 (COX-2), fatty acid amide hydrolase (FAAH), and diacylglycerol lipase alpha (DAGLα) also emerged as highly ranked nodes across multiple centrality measures. Closeness and eigenvector centrality further highlighted phytocannabinoids including cannabidiol (CBD), tetrahydrocannabivarin (THCV), and cannabidivarin (CBDV) as structurally well-connected components within the network. Community detection revealed a modular organization separating receptor-mediated signaling components from endocannabinoid metabolic processes, with clusters centered on CB&lt;sub&gt;1&lt;/sub&gt;/CB&lt;sub&gt;2&lt;/sub&gt; signaling machinery and enzymes such as FAAH and diacylglycerol lipase beta (DAGLβ), which are associated with 2-arachidonoylglycerol (2-AG) turnover. Perturbation analyses demonstrated that removal of dominant hubs, particularly CB&lt;sub&gt;1&lt;/sub&gt;, redistributed centrality and altered shortest-path structure, increasing the relative prominence of nodes such as CB&lt;sub&gt;2&lt;/sub&gt; and GPR55 while decreasing that of others such as DAGLβ and linoleoyl ethanolamide (LEA). These findings identify structurally influential and configuration-dependent nodes whose prominence becomes apparent through network-l","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13344038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147936795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabidiol and other non-psychotropic cannabinoids from Cannabis sativa as therapeutics for microglial-mediated neuroinflammation and neurodegeneration.","authors":"Daniel K Fowler, Tylor M Savage, Duncan I Mackie","doi":"10.1186/s42238-026-00445-5","DOIUrl":"10.1186/s42238-026-00445-5","url":null,"abstract":"<p><p>Non-psychotropic phytocannabinoids produced by Cannabis sativa, including cannabidiol, cannabigerol, cannabichromene and their varin and acidic analogs, are emerging as promising modulators of neuroinflammation, particularly through actions on microglia, the brain's resident immune cells. These compounds engage numerous receptors, ion channels, and intracellular signaling systems in microglia associated with neuroinflammation, and therefore are promising therapeutic candidates to treat chronic microglial inflammation-mediated neurodegenerative disorders. Despite substantial public and scientific interest, comprehensive evaluation of their mechanistic diversity, disease-relevant potential, and translational gaps across neurodegenerative disorders remains limited. Commonly, gaps also exist between cannabis breeders' and cultivators' knowledge of phytocannabinoid diversity and translational scientists' understanding of therapeutic potential. In this review, we first provide an in-depth overview of the main non-psychotropic phytocannabinoids, their biosynthesis, and the genetics that control their production in cannabis. We then summarize the known mechanisms of action for each cannabinoid in microglial-expressed molecular targets and signaling pathways relevant to neuroinflammation. Lastly, we review the effects of non-psychotropic phytocannabinoids in pre-clinical models and clinical trials of four neuroinflammation-associated neurodegenerative diseases: Alzheimer's disease, Parkinson's disease, multiple sclerosis, and Huntington's disease. Current evidence supports meaningful biological activity and complex cannabinoid-specific polypharmacology, yet substantial gaps persist, especially for cannabinoids other than cannabidiol; addressing these gaps in disease-relevant models will be essential for translating these compounds into future therapeutic strategies. Further, we anticipate the summarized information will foster collaboration between cannabis breeders/cultivators and applications scientists for therapeutic evaluation and development of emerging non-psychotropic phytocannabinoids.</p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13344039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147936759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}