Journal of cannabis research最新文献

{"title":"Decoding the antihypertensive mechanism of cannabidiol through integrative bioinformatics and machine learning.","authors":"Xin Jiang, Ziyue Zhou, Yuqin Liang, Yu Wang, Shumin Liu, Fang Lu","doi":"10.1186/s42238-026-00437-5","DOIUrl":"10.1186/s42238-026-00437-5","url":null,"abstract":"<p><p>BACKGROUND: Hypertension (HTN) results from intricate molecular mechanisms, making clinical remission difficult to achieve. This study explores the molecular pathways through which cannabidiol (CBD) may influence HTN. METHODS: Several RNA sequencing datasets related to HTN were retrieved from the GEO database and divided into training and validation sets. Candidate genes potentially associated with HTN were screened through differential expression analysis and weighted gene co-expression network analysis. The interactions and binding potential between CBD and key target proteins were then systematically investigated using bioinformatics, machine learning, immune cell infiltration analysis, and molecular dynamics simulation. RESULT: Seventy genes were identified as potential targets for CBD intervention in HTN. Machine learning analysis refined this list to five core genes: pyruvate kinase PKM (PKM), thyroid hormone receptor beta (THRB), aldo–keto reductase family 1 member B1 (AKR1B1), TGF-beta receptor type-1 (TGFBR1), and proto-oncogene tyrosine-protein kinase Src (SRC). Among these, PKM, THRB, AKR1B1, and SRC were significantly upregulated in HTN, while TGFBR1 was downregulated (P < 0.05). These genes formed a regulatory network, showing direct or indirect interactions, and were associated with infiltration levels of neutrophils and resting mast cells. Molecular dynamics simulation revealed that CBD exhibits strong binding specificity to these target proteins. CONCLUSION: This integrated analysis prioritized PKM, THRB, AKR1B1, TGFBR1, and SRC as candidate genes potentially associated with HTN progression. Molecular dynamics simulation suggested a favorable binding potential between CBD and these targets. These findings may provide supportive evidence for future studies exploring the potential mechanisms by which CBD may act in HTN. </p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13267379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794041","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":"Through the haze: a multinational cross-sectional comparison of cannabis risk knowledge gaps among young adults.","authors":"Anne Maiwald, Elena Gomes de Matos, Sally Olderbak, Larissa Schwarzkopf, Gabriele Koller, Reiner Hanewinkel, David Hammond, Eva Hoch","doi":"10.1186/s42238-026-00439-3","DOIUrl":"10.1186/s42238-026-00439-3","url":null,"abstract":"<p><p>BACKGROUND: Young adults report heightened cannabis use yet show gaps in cannabis-related risk knowledge. Risk knowledge gaps in young adults with diverse cannabis use experience and across countries with varying cannabis policies, as well as associations with knowledge levels were explored. METHODS: The International Cannabis Policy Study (ICPS) is a cross-sectional, web-based survey that uses non-probability sampling and post-stratification weighting. Data from the 2023 ICPS national surveys conducted in Canada, Germany and the UK were used. A total of n = 2,945 18- to 25-year-olds were included in the analyses (Canada: n = 2,047; Germany: n = 446; UK: n = 452). Risk knowledge gaps were assessed through 7 health-related risk items. Inaccurate responses were turned into an index variable to measure participants’ level of risk knowledge. Negative binomial regression models were used to examine associations between sociodemographic and use-related variables and knowledge level. RESULTS: Risk knowledge levels were highest among German participants, and lowest among UK participants. Some risks were better known than others across all countries. Risk knowledge was lowest among regular cannabis consumers, for whom being from the UK was associated with decreased knowledge levels (IRR = 1.227) and being at moderate risk of harm from use was associated with increased knowledge levels (IRR = 0.701). Among occasional consumers, age (IRR = 1.041), being male (IRR = 1.222) and being at moderate (IRR = 1.236) and high (IRR = 1.818) risk of harm from use were associated with decreased risk knowledge, whereas peer use (IRR = 0.718) was associated with increased risk knowledge. CONCLUSIONS: This study showed that there are differences in the perception of cannabis risks among young adults, which are associated with individual consumption patterns as well as country-specific and sociodemographic factors. Findings extend the current understanding of differences and similarities in risk knowledge gaps among young adults across different countries, allowing for a more tailored risk education towards the needs of this target group. </p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":"8 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794002","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":"The greater the pleiotropic effects, the greater the benefits - cannabis as a \"biopsychosocial\" drug: a mixed-methods study on chronic non-cancer pain.","authors":"Inês C A Pombeiro Stein, Franziska Fitzner, Martin Dusch, Christian S Kessler, Jan Moritz Fischer, Farid-Ihab Kandil, Felix Freigang, Matthias Karst","doi":"10.1186/s42238-026-00440-w","DOIUrl":"10.1186/s42238-026-00440-w","url":null,"abstract":"<p><p>BACKGROUND: Against the background of widely inconsistent data from randomized controlled trials (RCT), the use of cannabis-based medicines (CBM) from the perspective of patients with chronic non-cancer pain (CNCP) was described. METHODS: Based on a purposive/convenient sampling, patients were recruited from the Pain Clinic of Hannover Medical School who had been using CBM prescribed by a doctor for at least 6 months. The patients discussed their experiences with CBM in semi-structured individual interviews. The interview transcripts were coded and analyzed using a modified grounded theory approach with the help of MAXQDA®. In addition, the Treatment Satisfaction Questionnaire with Medication (TSQM) was used. RESULTS: Theoretical saturation was reached after 32 interviews. Open and selective coding revealed the overarching phenomenon of “subjective pain experience under CBM therapy”, with one of the main themes being the “effect of CBM”. This revealed the categories “effect on pain” and “psychological” and “somatic effect”. The most important concepts were “pain intensity”, “pain management”, “stress management”, “musculoskeletal system”, and “sleep quality.” Constructing a theoretical framework 4 groups of responses to CBM treatment were identified. The focus is either on (I) pain reduction, (II) pain coping, (III) reduced stress or (IV) multidimensional aspects. When this classification was applied to topic of quality of life (QOL), the greatest effectiveness and highest overall satisfaction were found in group (IV). Mixed methods showed a continuous increase in the perceived effectiveness of CBM on pain-centered complaints from group (I) to (IV). CONCLUSIONS: In line with the biopsychosocial understanding of chronic pain, it appears that those CNCP patients who benefit most from CBM are those who show the most far-reaching effects on both a physical and psychological level. The pleiotropic effects of CBM may be responsible for this. Based on these results, interdisciplinary prospective research appears sensible and necessary to further and systematically investigate this clinically relevant topic. TRIAL REGISTRATION: This study was registered with the German Clinical Trials Register (DRKS00037434), after approval by the local ethics committee (No. 8391_B0-K_2019). </p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":"8 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794031","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":"Factors associated with youth opposition or support for cannabis legalization in Lebanon.","authors":"Joseph El-Khoury, Andre Slim, Michele Cherro, Lilian A Ghandour","doi":"10.1186/s42238-026-00426-8","DOIUrl":"10.1186/s42238-026-00426-8","url":null,"abstract":"<p><p>BACKGROUND: In 2020, Lebanon initiated the legalization process for the cultivation of cannabis for medical and industrial purposes only. This paper aims to examine the factors associated with youth attitude towards the legalization of medicinal and recreational cannabis in Lebanon. METHODS: In early 2020, a total of 1,230 young adults aged 18 to 24 participated in an anonymous online survey. The main outcome was the support/opposition of medicinal and recreational cannabis legalization in Lebanon. RESULTS: Participants who were male, non-students, working, and perceived themselves to be relatively well-off were more likely to be in the supportive rather than oppositional group for attitude towards medicinal (p-value < 0.0001). Participants who were also more likely to be supportive of legalization (rather than opposed) were: (1) participants who correctly answered the question regarding the purpose of the legislative change in Lebanon; (2) young adults who perceived cannabis as not harmful; (3) young adults who reported ever using cannabis in combination with alcohol or other drugs; and (4) students who did not think that legalization of cannabis for medicinal use or recreational use would affect their use of other illegal drugs. CONCLUSION: Young adults surveyed were generally supportive of cannabis legalization coupled with generally good awareness of the potential risks and harms. From an equity perspective, legalization could create disproportionate harms in different groups of young adults, and therefore any legislative changes should be accompanied by implementing robust public health strategies to address knowledge gaps and mitigate risks in young adults. </p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13220542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147719280","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":"Lessons learned: challenges in recruiting and engaging people with heavy cannabis use for online interventions in Canada.","authors":"Karli K Rysen, Corey S Mackenzie, Julian M Carusone, Michael P Schaub, Andreas Wenger, Harold Wallbridge, Jason D Edgerton, Richard Kruk, Matthew T Keough","doi":"10.1186/s42238-026-00425-9","DOIUrl":"10.1186/s42238-026-00425-9","url":null,"abstract":"<p><p>BACKGROUND: People who seek treatment often disengage between completing screening and starting treatment. Among those who begin treatment, many have low completion of program content and are lost to follow up. Currently, little is known about predictive factors of treatment initiation and engagement. The aims of this secondary analysis of the Canadian CANreduce program were to discuss the practicality of a randomized controlled trial for online heavy cannabis use treatment and to examine predictors of treatment initiation and engagement in the Canadian CANreduce program. METHOD: The CANreduce intervention was pre-registered on clinicaltrials.gov for traceability (ID: NCT04965012). Statistical models were organized into three conceptual predictor groupings using baseline data: individual cannabis-specific factors, mental health and other substance use factors, and treatment belief factors. Binary logistic regressions examined which factors predicted treatment initiation in the CANreduce treatment program and multiple regression analyses examined which factors predicted percentage of the CANreduce program modules completed among participants who initiated treatment. RESULTS: Despite following the core elements of published treatment retention protocols, challenges in recruitment were evident. Of 928 people who created a profile on the website and began screeners, 86.3% (n = 801) completed screeners. Of the 801 who completed screeners, 31.3% (n = 251) were eligible for the program. Of those eligible and assigned to active treatment, 54.3% (n = 51) assigned to the therapist condition and 45.7% (n = 43) assigned to the research assistant condition initiated treatment. Treatment initiation predictors included higher cannabis use problems score, lower family history density, increased alcohol use frequency, and more positive attitudes towards treatment. Treatment engagement (percentage of program completed) predictors included increased social motives for cannabis use and more positive attitudes towards treatment. DISCUSSION: This secondary analysis shifts the focus from treatment efficacy to pre-treatment attrition and early engagement in an online cannabis intervention. Substantial recruitment and initiation challenges were observed, highlighting vulnerabilities in the treatment-seeking pathway before content is accessed. By identifying predictors of treatment initiation and module completion, this study offers practical “lessons learned” to inform recruitment and engagement strategies in future online cannabis trials. </p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13224416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147701448","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":"Prenylated apigenin derivatives from Cannabis sativa L.: isolation, biosynthesis, and anti-inflammatory properties.","authors":"Ulli K C Bodnar, Jackson J Villemaire-McCutcheon, Kelly F Boddington, Eric Soubeyrand, M Sameer Al-Abdul-Wahid, Hannah N Robeson, Jasmin Lalonde, José A Casaretto, Tariq A Akhtar","doi":"10.1186/s42238-026-00438-4","DOIUrl":"10.1186/s42238-026-00438-4","url":null,"abstract":"<p><strong>Background: </strong>Cannabis sativa L. accumulates a wide array of specialized compounds, many of which are non-psychotropic and show significant promise in medical and therapeutic applications. One such group of C. sativa compounds is prenylated flavonoids, which have emerged as potential treatments for chronic pain and inflammation. Accordingly, the aim of this study was to isolate, identify, and synthesize prenylated flavonoids from C. sativa and test their efficacy as anti-inflammatory agents.</p><p><strong>Methods: </strong>An enriched polyphenol extract from C. sativa was fractionated using flash chromatography and high-performance liquid chromatography to isolate prenylated flavonoids. Liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy were employed to determine their structures. Phylogenomic and classical biochemical approaches were combined to identify the enzyme involved in the biosynthesis of the isolated compounds. Finally, these prenylated flavonoids were tested to determine their inhibitory properties against microsomal prostaglandin E synthase-1 (mPGES-1) activity.</p><p><strong>Results: </strong>Two prenylated flavonoids were isolated from the aerial parts of the C. sativa plant using classical chromatographic procedures and identified as 6-prenylapigenin (6-PA) and 6-geranylapigenin (6-GA). A C. sativa prenyltransferase (CsPT3) from the UbiA superfamily was identified to complete the final prenylation step in 6-PA and 6-GA biosynthesis from the widespread plant flavonoid known as apigenin. The inhibitory potentials of 6-PA and 6-GA against mPGES-1 activity were approximately as effective as, or better than, that of a leading commercially available inhibitor, MK-886. Molecular docking simulations confirmed strong binding affinities of 6-PA and 6-GA to mPGES-1 compared to its natural substrate.</p><p><strong>Conclusions: </strong>6-PA and 6-GA are prenylated derivatives of the widespread plant flavonoid known as apigenin. These non-psychotropic flavonoids accumulate in C. sativa and exhibit potent inhibition of mPGES-1, a chief mediator in the pro-inflammatory pathway. Identification of the final step in 6-PA and 6-GA biosynthesis, together with their now-established anti-inflammatory activity, presents propitious biotechnological avenues for these therapeutically relevant C. sativa compounds.</p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694596","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":"In silico receptor binding and ex vivo nasal epithelial membrane permeation studies of selected phytocannabinoids.","authors":"Suzanne E Van Niekerk, Theunis Cloete, Frank Van der Kooy, Josias H Hamman","doi":"10.1186/s42238-025-00363-y","DOIUrl":"10.1186/s42238-025-00363-y","url":null,"abstract":"<p><p>BACKGROUND: Headache disorders, specifically migraine headaches, are highly debilitating neurological disorders, with the potential to incapacitate an individual for several hours. Cannabinoid receptors are present in both peripheral and central nervous tissue, which serve as a potential target for the treatment of migraine. Cannabis sativa is a medicinal plant that has been used as self-medication for the treatment of headaches, but insufficient scientific information is currently available regarding their interactions with receptors, as well as intranasal delivery. The intranasal route of administration offers the potential for systemic delivery, as well as delivery into the brain. Nose-to-brain delivery offers a pathway directly to the brain via olfactory epithelium and trigeminal nerves and bypasses both the first-pass metabolism and the blood-brain-barrier (BBB). METHODS: Known phytochemicals of C. sativa were docked in silico into the active site of the 6KPC crystal structure of the cannabinoid type 2 (CB2) receptor to screen for receptor affinity. Ex vivo permeation studies were done on these four selected cannabinoid compounds across excised sheep nasal epithelial tissue. RESULTS: Four cannabinoid compounds were identified with affinity for the CB2 receptor that may provide activity against migraine, namely cannabicyclol, cannabidiolic acid, cannabicitran and cannabielsoin. The ex vivo membrane permeation results revealed that some of the cannabinoids can be delivered to a similar extent than moderately permeable model drugs across nasal epithelium for systemic delivery and potentially also for direct nose-to-brain delivery. CONCLUSION: Through affinity for the CB2 receptor, the identified compounds have shown potential in migraine treatment. There is also potential for nose-to-brain delivery. </p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147701404","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":"Electrophysiological modulation of pain‑related sodium channels by cannabinoids: a systematic review.","authors":"Samuel Gonçalves Castro, Sarah Eduarda Silva, Julio Cesar Moreira Brito, Alessandra Matavel","doi":"10.1186/s42238-026-00436-6","DOIUrl":"10.1186/s42238-026-00436-6","url":null,"abstract":"<p><p>BACKGROUND: Voltage-gated sodium channels regulate dorsal root ganglion excitability and are critical for nociceptive transmission. Cannabidiol (CBD) and related phytocannabinoids have been proposed to modulate these channels, offering potential non-opioid analgesic strategies. This systematic review evaluated their in vitro effects on pain-related sodium channels, focusing on electrophysiological and biophysical mechanisms. METHODS: Following PRISMA guidelines, Embase®, LILACS®, PubMed®/MEDLINE®, and Scopus® were searched using the SPIDER strategy. Eligible studies evaluated CBD or its derivatives on voltage-gated sodium channels Nav1.3, Nav1.6, Nav1.7, Nav1.8, and Nav1.9 through electrophysiological assays. Data extraction and analysis were conducted independently by two reviewers, with inter-rater agreement assessed by Cohen’s kappa. Seven studies met the inclusion criteria. RESULTS: CBD consistently inhibited sodium currents with IC₅₀ values in the low micromolar range (2–3.3 µM), reduced action potential firing, induced hyperpolarizing shifts in steady-state inactivation, and delayed recovery from inactivation. Other phytocannabinoids, such as cannabigerol, cannabinol, cannabigerolic acid, and cannabidivarinic acid, also inhibited sodium channels, though with variable potency and distinct effects on channel gating. CONCLUSION: Cannabinoids, particularly CBD, act as non-selective inhibitors of voltage-gated sodium channels implicated in pain signaling. Their ability to stabilize inactivated channel states and reduce neuronal excitability supports their therapeutic potential in neuropathic pain. These findings highlight the relevance of phytocannabinoids as promising candidates for the development of non-opioid analgesics. </p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13196123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694534","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":"Association between cannabis use and major depressive disorder: a population-based cross-sectional study.","authors":"Yanzhe Ning, Jigao Sun, Jiayan Zhou, Yihao Wang, Zucheng Shang, Mengfan Li, Hongzheng Li, Ya Xuan Sun, Ying Wu, Themistocles L Assimes, Hui Zhang, Guang Chen","doi":"10.1186/s42238-026-00396-x","DOIUrl":"10.1186/s42238-026-00396-x","url":null,"abstract":"<p><p>BACKGROUND: Major depressive disorder (MDD) is a chronic, recurrent psychiatric illness with challenging management, partly due to the heterogeneity of clinical presentations, unpredictable course and episodes, and variable treatment responses. Cannabis may alleviate depression by promoting glutamate, GABA, and dopamine, but results from previous studies remain controversial or inconsistent. In this study, we aimed to investigate the association between cannabis use and the prevalence and severity of MDD in adults. METHODS: This study utilized data from the UK Biobank, with cannabis use as the exposure variable and depression as the outcome. Depression was ascertained using six distinct definitions, including broad clinical diagnosis, symptom-based criteria, self-reported depression, electronic health record-based diagnoses, and a strictly defined diagnostic category based on guideline criteria. C-reactive protein (CRP) levels and markers of biological aging were extracted from the database and analyzed as potential mediators. Both logistic and linear regression models were employed to examine the correlation. Subgroup analyses were used to explore potential effect modifiers while sensitivity analyses were used to ensure the robustness of the regression models. RESULTS: A total of 33,749 individuals were included in the final analysis, with 50.5% being male. Cannabis use was associated with a 27% increase in the odds of depression prevalence (adjusted odds ratio [OR] = 1.27; 95% confidence interval [CI] = 1.18–1.38). No significant association was observed between the frequency of cannabis use and the number of depression episodes. Subgroup analyses revealed that, among current smokers, cannabis use was not significantly associated with increased odds of depression (OR = 1.09; 95% CI = 0.89–1.35). CRP levels may mediate this relationship, whereas markers of biological aging did not. Sensitivity analyses conducted a priori demonstrated consistent results, supporting the robustness of these findings. CONCLUSION: Cannabis use is associated with elevated odds of depression, with a comparatively attenuated impact observed among current smokers. However, the quantity of cannabis consumed did not correlate with the number of depression episodes. Further research employing longitudinal cohort studies or controlled clinical trials is needed to further inform evidence-based depression management strategies. </p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13255423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694564","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":"Astrocytic GPR55 receptors promote glycolysis.","authors":"Cândida Dias, Erik Keimpema, Rui A Carvalho, Daniela Madeira, Liliana Dias, Ana Ledo, João Laranjinha, Rodrigo A Cunha, Paula Agostinho, Tibor Harkany, Attila Köfalvi","doi":"10.1186/s42238-026-00407-x","DOIUrl":"10.1186/s42238-026-00407-x","url":null,"abstract":"<p><p>BACKGROUND: The endocannabinoid system is closely associated with systemic and cellular energy metabolism in mammals. We previously demonstrated that the cannabinoid receptors CB1 and CB2 play important roles in cerebral glucose metabolism. GPR55, a paracannabinoid receptor, has been implicated in systemic metabolic regulation and in diseases such as intractable epilepsy, diabetes, and cancer. In the present study, we investigated whether GPR55 also influences brain glucose metabolism. METHODS: Acute hippocampal and cortical slices and primary astrocytic cultures from C57BL/6 mice and Wistar rats were used. Quantitative polymerase chain reaction (qPCR) was used to assess Cnr1 and Gpr55 gene expression levels, and [³H]deoxyglucose/[¹⁴C]-U-glucose uptake assays, high-resolution respirometry using the Oroboros O2k system, and proton nuclear magnetic resonance ([¹H]-NMR) spectroscopy were employed to assess metabolic activity upon receptor activation. RESULTS: qPCR analysis revealed that Cnr1 mRNA dominated in neurons, whereas Gpr55 was predominantly expressed in primary astrocytes. Δ⁹-Tetrahydrocannabinol (Δ⁹-THC), the GPR55-selective synthetic agonist O-1602, the endogenous GPR55 agonists, L-α-lysophosphatidylinositol (LPI) and palmitoylethanolamide (PEA), together with the mixed CB1 receptor antagonist/GPR55 agonist AM251, invariably and significantly stimulated glucose uptake and metabolism in brain preparations at nanomolar concentrations ex vivo. The GPR55-selective antagonist CID16020046 (1 µM) abolished the effects of the GPR55 agonists, as did pretreatment with the cytosolic Ca2+ chelator BAPTA-AM (30 µM). While LPI did not alter oxidative metabolism in either astrocytes or neurons, it selectively stimulated glycolysis and lactate release in astrocytes. CONCLUSIONS: Our findings reveal a novel role for GPR55 in astrocytes. By enhancing glycolytic activity in these cells, GPR55 is likely poised to support, even if indirectly, the energy demands of synaptic transmission. </p>","PeriodicalId":101310,"journal":{"name":"Journal of cannabis research","volume":"8 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147648267","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}