{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:51:49Z","timestamp":1786121509272,"version":"build-2736575974"},"reference-count":104,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014064","name":"Universidad de Salamanca","doi-asserted-by":"publisher","award":["Art 83. 2019\/00106\/001; LBZ5"],"award-info":[{"award-number":["Art 83. 2019\/00106\/001; LBZ5"]}],"id":[{"id":"10.13039\/501100014064","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014064","name":"Universidad de Salamanca","doi-asserted-by":"publisher","award":["Art 83. 2019\/00006\/001; LAZ5"],"award-info":[{"award-number":["Art 83. 2019\/00006\/001; LAZ5"]}],"id":[{"id":"10.13039\/501100014064","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014180","name":"Junta de Castilla y Le\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014180","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Roughly one-third of patients with epilepsy remain drug resistant, underscoring the need for novel therapeutic strategies. Although cannabidiol (CBD) has recently been approved for specific epileptic encephalopathies, its anticonvulsant mechanisms and the influence of biological sex on treatment response remain incompletely understood. In this preclinical study, we evaluated the efficacy, tolerability, pharmacokinetics, and molecular effects of CBD in the GASH\/Sal hamster, a genetic model of audiogenic generalized tonic\u2013clonic seizures. Animals received intraperitoneal CBD (200\u00a0mg\/kg) either acutely or chronically for 14 days. CBD concentrations were measured in serum and brain, while seizure severity, latency, and neuroethological parameters were assessed following acoustic seizure induction. Safety was evaluated through body weight, hematological, and biochemical analyses, and gene expression profiling was performed in the inferior colliculus, the primary epileptogenic focus. CBD achieved measurable systemic and brain exposure after both acute and chronic administration, despite substantial inter-individual variability and no significant sex differences in drug concentrations. CBD reduced audiogenic seizure severity in a time-dependent manner, with greater protection after chronic treatment. CBD also prolonged latency to seizure onset in both sexes (earlier in females). Although complete seizure suppression was more frequent in females than males (37.5% vs. 12.5% after chronic treatment), direct sex comparisons did not reach statistical significance. Notably, higher serum and brain CBD concentrations were associated with lower seizure severity. Chronic CBD administration was well tolerated in both sexes, affecting selected hematological parameters without altering body weight or liver function. Gene expression profiling revealed that transcriptional organization of the inferior colliculus was driven predominantly by biological sex rather than by seizure induction or CBD treatment. Marked sex-dependent differences were observed in serotonergic, endocannabinoid, purinergic, and Sigmar1-related neuroprotective pathways. Within this molecular context, seizure stimulation modulated\n                    <jats:italic>Trpv1<\/jats:italic>\n                    and\n                    <jats:italic>Slc29a1<\/jats:italic>\n                    , whereas chronic CBD induced pathway-specific, sex-dependent changes involving\n                    <jats:italic>5-Htr1a<\/jats:italic>\n                    ,\n                    <jats:italic>Adora1<\/jats:italic>\n                    , and\n                    <jats:italic>Cnr1<\/jats:italic>\n                    , without eliciting widespread transcriptional remodeling. Collectively, these findings identify CBD as a well-tolerated anticonvulsant in the GASH\/Sal model and suggest that pharmacokinetic exposure and the sex-specific molecular organization of the epileptogenic focus contribute to variability in treatment response, highlighting the importance of considering biological sex in cannabinoid-based epilepsy research.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1745696","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T05:28:04Z","timestamp":1786080484000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Anticonvulsant effects, safety, and sex-dependent molecular signatures of cannabidiol treatment in a preclinical model of audiogenic epilepsy"],"prefix":"10.3389","volume":"17","author":[{"given":"Giselda","family":"Cabral-Pereira","sequence":"first","affiliation":[{"name":"Instituto de Neurociencias de Castilla y Le\u00f3n (INCYL), Universidad de Salamanca","place":["Salamanca, Spain"]},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Universidad de Salamanca","place":["Salamanca, Spain"]},{"name":"Instituto de Neurociencias UMH-CSIC, Universidad Miguel Hern\u00e1ndez and Consejo Superior de Investigaciones Cient\u00edficas","place":["Sant Joan d\u2019Alacant, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolores E.","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias de Castilla y Le\u00f3n (INCYL), Universidad de Salamanca","place":["Salamanca, Spain"]},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Universidad de Salamanca","place":["Salamanca, Spain"]},{"name":"Departamento de Biolog\u00eda Celular y Patolog\u00eda, Facultad de Medicina, Universidad de Salamanca","place":["Salamanca, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"G\u00f3mez-Nieto","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias de Castilla y Le\u00f3n (INCYL), Universidad de Salamanca","place":["Salamanca, Spain"]},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Universidad de Salamanca","place":["Salamanca, Spain"]},{"name":"Departamento de Biolog\u00eda Celular y Patolog\u00eda, Facultad de Medicina, Universidad de Salamanca","place":["Salamanca, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1128\/am.19.4.704-705.1970","article-title":"Errors related to different techniques of intraperitoneal injection in mice","volume":"19","author":"Arioli","year":"1970","journal-title":"Appl. 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