{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T22:44:01Z","timestamp":1773355441299,"version":"3.50.1"},"posted":{"date-parts":[[2026,3,9]]},"group-title":"Animal Behavior and Cognition","reference-count":105,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH NIDA","award":["R073239075"],"award-info":[{"award-number":["R073239075"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Cannabis contains many bioactive compounds, including \u03949-Tetrahydrocannabinol (THC) and cannabidiol (CBD), which influence behavior through complex pharmacological interactions with endogenous targets. This study examines whether CBD influences THC-induced changes in motor activity, hypothermia, and antinociception traits across different THC:CBD ratios, sexes, and genetic backgrounds. Traits were measured in C57BL\/6J (B6) and DBA\/2J (D2) mice of both sexes following baseline intraperitoneal (\n                  <jats:italic>i.p.<\/jats:italic>\n                  ) injection of vehicle (VEH) and two consecutive daily doses of VEH or THC (10 mg\/kg) alone or in combination with 0.56, 5, or 10 mg\/kg CBD (THC:0.56CBD, THC:5CBD, or THC:10CBD, respectively). Motor activity and hypothermia were quantified daily from 0 to 120 min following injection and antinociception was measured daily at 60 min. We found that CBD alters THC-induced changes in motor activity and hypothermia as a function of day, dose, time, sex, and strain. In D2 females, CBD dose-dependently attenuated the hypolocomotor effects of THC immediately following acute injection and enhanced these effects later at 75 min. Following repeated exposure, CBD dose-dependently enhanced THC-induced hypolocomotion in B6 females at 75 min and in D2 males at 30 min while attenuating THC-induced hypolocomotion in D2 females immediately following injection. In D2 females, CBD dose-dependently attenuated THC-induced hypothermia at 15 min and enhanced hypothermia relative to THC at 30 min in D2 males following acute injection. After repeated exposure, CBD dose-dependently enhanced THC-induced hypothermia in B6 females at 15 min and in D2 males from 30 to 120 mins, while attenuating hypothermia in D2 females at 30 min. No significant effects of CBD on antinociception were observed. Our results indicate that CBD can modulate some THC-induced traits acutely and after repeated exposure. Regulation of THC-induced behavioral responses is dependent on CBD dose, genetic background, and sex. A candidate gene search using brain gene expression in recombinant inbred mice revealed greater genetic variation in ion channel genes relative to key metabolic genes, suggesting an underlying pharmacodynamic mechanism. Future research and validation of molecular mechanisms underlying these differences is expected to enhance our understanding of potential health risks and clinical relevance of cannabis and cannabinoid compounds containing THC and CBD.\n                <\/jats:p>","DOI":"10.64898\/2026.03.05.709920","type":"posted-content","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T20:15:25Z","timestamp":1773087325000},"source":"Crossref","is-referenced-by-count":0,"title":["Cannabidiol dose modulates behavioral response to acute and repeated administration of \u03949-Tetrahydrocannabinol by strain and sex"],"prefix":"10.64898","author":[{"given":"Sheena","family":"Saxena","sequence":"first","affiliation":[{"name":"Department of Genetics, Genomics and Informatics, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A.","family":"Duecker","sequence":"additional","affiliation":[{"name":"Department of Genetics, Genomics and Informatics, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukmon M.","family":"Raji","sequence":"additional","affiliation":[{"name":"Department of Genetics, Genomics and Informatics, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine E.","family":"Watkins","sequence":"additional","affiliation":[{"name":"Department of Genetics, Genomics and Informatics, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sufiya","family":"Khanam","sequence":"additional","affiliation":[{"name":"Department of Genetics, Genomics and Informatics, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4985-6729","authenticated-orcid":false,"given":"Byron C.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Genetics, Genomics and Informatics, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"II","given":"Bob M.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4909-635X","authenticated-orcid":false,"given":"Megan K.","family":"Mulligan","sequence":"additional","affiliation":[{"name":"Department of Genetics, Genomics and Informatics, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"1","key":"2026031204550967000_2026.03.05.709920v1.1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s42238-022-00170-9","article-title":"Systematic combinations of major cannabinoid and terpene contents in Cannabis flower and patient outcomes: a proof-of-concept assessment of the Vigil Index of Cannabis Chemovars","volume":"5","year":"2023","journal-title":"J Cannabis Res"},{"key":"2026031204550967000_2026.03.05.709920v1.2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0267498"},{"issue":"9","key":"2026031204550967000_2026.03.05.709920v1.3","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.3390\/ph3092799","article-title":"Vulnerability Factors for the Psychiatric and Behavioral Effects of Cannabis","volume":"3","year":"2010","journal-title":"Pharmaceuticals (Basel"},{"key":"2026031204550967000_2026.03.05.709920v1.4","doi-asserted-by":"crossref","unstructured":"Kitdumrongthum S , Trachootham D . An Individuality of Response to Cannabinoids: Challenges in Safety and Efficacy of Cannabis Products. Molecules. 2023;28(6).","DOI":"10.3390\/molecules28062791"},{"issue":"25","key":"2026031204550967000_2026.03.05.709920v1.5","doi-asserted-by":"crossref","first-page":"14099","DOI":"10.1021\/acs.jafc.3c06616","article-title":"Chemical Composition of Commercial Cannabis","volume":"72","year":"2024","journal-title":"J Agric Food Chem"},{"issue":"25","key":"2026031204550967000_2026.03.05.709920v1.6","doi-asserted-by":"crossref","first-page":"14479","DOI":"10.1021\/acs.jafc.4c01418","article-title":"Correction to \u201cChemical Composition of Commercial Cannabis","volume":"72","year":"2024","journal-title":"J Agric Food Chem"},{"key":"2026031204550967000_2026.03.05.709920v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2017.10.037"},{"issue":"1","key":"2026031204550967000_2026.03.05.709920v1.8","doi-asserted-by":"crossref","first-page":"e13092","DOI":"10.1111\/adb.13092","article-title":"Effects of cannabidiol in cannabis flower: Implications for harm reduction","volume":"27","year":"2022","journal-title":"Addict Biol"},{"issue":"1-3","key":"2026031204550967000_2026.03.05.709920v1.9","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.drugalcdep.2007.11.017","article-title":"Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Delta(9)-tetrahydrocannabinol","volume":"94","year":"2008","journal-title":"Drug Alcohol Depend"},{"key":"2026031204550967000_2026.03.05.709920v1.10","doi-asserted-by":"publisher","DOI":"10.1177\/0269881112460109"},{"key":"2026031204550967000_2026.03.05.709920v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2009.04.010"},{"issue":"11","key":"2026031204550967000_2026.03.05.709920v1.12","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1007\/s00213-018-5036-z","article-title":"Cannabidiol modulation of antinociceptive tolerance to Delta(9)-tetrahydrocannabinol","volume":"235","year":"2018","journal-title":"Psychopharmacology (Berl"},{"issue":"1","key":"2026031204550967000_2026.03.05.709920v1.13","first-page":"235","article-title":"Chronic Adolescent Delta(9)-Tetrahydrocannabinol Treatment of Male Mice Leads to Long-Term Cognitive and Behavioral Dysfunction","volume":"2","year":"2017","journal-title":"Which Are Prevented by Concurrent Cannabidiol Treatment. Cannabis Cannabinoid Res"},{"key":"2026031204550967000_2026.03.05.709920v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2017.01.046"},{"key":"2026031204550967000_2026.03.05.709920v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.367"},{"issue":"5","key":"2026031204550967000_2026.03.05.709920v1.16","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1089\/can.2021.0166","article-title":"Delta-9-Tetrahydrocannabinol, Cannabidiol, and Acute Psychotomimetic States: A Balancing Act of the Principal Phyto-Cannabinoids on Human Brain and Behavior","volume":"8","year":"2023","journal-title":". Cannabis Cannabinoid Res"},{"key":"2026031204550967000_2026.03.05.709920v1.17","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0708-19.2019"},{"key":"2026031204550967000_2026.03.05.709920v1.18","doi-asserted-by":"crossref","unstructured":"Gabaglio M , Zamberletti E , Manenti C , Parolaro D , Rubino T . Long-Term Consequences of Adolescent Exposure to THC-Rich\/CBD-Poor and CBD-Rich\/THC-Poor Combinations: A Comparison with Pure THC Treatment in Female Rats. Int J Mol Sci. 2021;22(16).","DOI":"10.3390\/ijms22168899"},{"key":"2026031204550967000_2026.03.05.709920v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2009.06.008"},{"issue":"1","key":"2026031204550967000_2026.03.05.709920v1.20","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jpain.2022.09.002","article-title":"Cannabidiol and Delta-9-Tetrahydrocannabinol Interactions in Male and Female Rats With Persistent Inflammatory Pain","volume":"24","year":"2023","journal-title":"J Pain"},{"issue":"12","key":"2026031204550967000_2026.03.05.709920v1.21","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1097\/j.pain.0000000000001051","article-title":"Cannabis constituent synergy in a mouse neuropathic pain model","volume":"158","year":"2017","journal-title":"Pain"},{"key":"2026031204550967000_2026.03.05.709920v1.22","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X21666230912101441"},{"key":"2026031204550967000_2026.03.05.709920v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-022-01478-z"},{"key":"2026031204550967000_2026.03.05.709920v1.24","doi-asserted-by":"crossref","unstructured":"MacNicol E , Kokkinou M , Serrano Navacerrada ME , Smith DM , Li J , Simmons C , et al. Acute cannabidiol (CBD), tetrahydrocannabinol (THC) and their mixture (THC:CBD) exert differential effects on brain activity and blood flow in rats: A translational neuroimaging study. J Psychopharmacol. 2025:2698811251360745.","DOI":"10.1177\/02698811251360745"},{"issue":"1","key":"2026031204550967000_2026.03.05.709920v1.25","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/s41398-018-0191-x","article-title":"Individual and combined effects of acute delta-9-tetrahydrocannabinol and cannabidiol on psychotomimetic symptoms and memory function","volume":"8","year":"2018","journal-title":"Transl Psychiatry"},{"issue":"11","key":"2026031204550967000_2026.03.05.709920v1.26","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/j.annonc.2020.07.020","article-title":"Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial","volume":"31","year":"2020","journal-title":"Ann Oncol"},{"key":"2026031204550967000_2026.03.05.709920v1.27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01921"},{"key":"2026031204550967000_2026.03.05.709920v1.28","doi-asserted-by":"crossref","first-page":"106588","DOI":"10.1016\/j.nbd.2024.106588","article-title":"Prenatal tetrahydrocannabinol and cannabidiol exposure produce sex-specific pathophysiological phenotypes in the adolescent prefrontal cortex and hippocampus","volume":"199","year":"2024","journal-title":"Neurobiol Dis"},{"issue":"1","key":"2026031204550967000_2026.03.05.709920v1.29","doi-asserted-by":"crossref","first-page":"sgab052","DOI":"10.1093\/schizbullopen\/sgab052","article-title":"Cannabis Vapor Exposure Alters Neural Circuit Oscillatory Activity in a Neurodevelopmental Model of Schizophrenia: Exploring the Differential Impact of Cannabis Constituents","volume":"3","year":"2022","journal-title":"Schizophr Bull Open"},{"issue":"6","key":"2026031204550967000_2026.03.05.709920v1.30","doi-asserted-by":"crossref","first-page":"e0234176","DOI":"10.1371\/journal.pone.0234176","article-title":"Evaluation of the preclinical analgesic efficacy of naturally derived, orally administered oil forms of Delta9-tetrahydrocannabinol (THC), cannabidiol (CBD), and their 1:1 combination","volume":"15","year":"2020","journal-title":"PLoS One"},{"issue":"1","key":"2026031204550967000_2026.03.05.709920v1.31","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1089\/can.2020.0083","article-title":"Cannabidiol Interferes with Establishment of Delta(9)-Tetrahydrocannabinol-Induced Nausea Through a 5-HT(1A) Mechanism","volume":"7","year":"2022","journal-title":"Cannabis Cannabinoid Res"},{"key":"2026031204550967000_2026.03.05.709920v1.32","doi-asserted-by":"crossref","first-page":"576877","DOI":"10.3389\/fpsyt.2020.576877","article-title":"Effects of Cannabidiol and Delta-9-Tetrahydrocannabinol on Emotion, Cognition, and Attention: A Double-Blind, Placebo-Controlled, Randomized Experimental Trial in Healthy Volunteers","volume":"11","year":"2020","journal-title":"Front Psychiatry"},{"issue":"2","key":"2026031204550967000_2026.03.05.709920v1.33","doi-asserted-by":"crossref","first-page":"3331024251314487","DOI":"10.1177\/03331024251314487","article-title":"Combined effects of cannabidiol and Delta9-tetrahydrocannabinol alleviate migraine-like symptoms in mice","volume":"45","year":"2025","journal-title":"Cephalalgia"},{"issue":"4","key":"2026031204550967000_2026.03.05.709920v1.34","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1089\/can.2023.0187","article-title":"Acute and Extended Anxiolytic Effects of Cannabidiol in Cannabis Flower: A Quasi-Experimental ad libitum Use Study","volume":"9","year":"2024","journal-title":"Cannabis Cannabinoid Res"},{"issue":"1","key":"2026031204550967000_2026.03.05.709920v1.35","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s42238-025-00286-8","article-title":"Effects of five cannabis oils with different CBD: THC ratios and terpenes on hypertension, dyslipidemia, hepatic steatosis, oxidative stress, and CB1 receptor in an experimental model","volume":"7","year":"2025","journal-title":"J Cannabis Res"},{"issue":"5","key":"2026031204550967000_2026.03.05.709920v1.36","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1002\/cpt.3381","article-title":"Cannabidiol Increases Psychotropic Effects and Plasma Concentrations of Delta(9)-Tetrahydrocannabinol Without Improving Its Analgesic Properties","volume":"116","year":"2024","journal-title":"Clin Pharmacol Ther"},{"issue":"3","key":"2026031204550967000_2026.03.05.709920v1.37","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1089\/can.2021.0015","article-title":"Perinatal CBD or THC Exposure Results in Lasting Resistance to Fluoxetine in the Forced Swim Test: Reversal by Fatty Acid Amide Hydrolase Inhibition","volume":"7","year":"2022","journal-title":"Cannabis Cannabinoid Res"},{"key":"2026031204550967000_2026.03.05.709920v1.38","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2019.00174"},{"issue":"11","key":"2026031204550967000_2026.03.05.709920v1.39","doi-asserted-by":"crossref","first-page":"3731","DOI":"10.1007\/s00213-022-06248-9","article-title":"Cannabis containing equivalent concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) induces less state anxiety than THC-dominant cannabis","volume":"239","year":"2022","journal-title":"Psychopharmacology (Berl"},{"issue":"1","key":"2026031204550967000_2026.03.05.709920v1.40","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s00406-019-00978-2","article-title":"A randomised controlled trial of vaporised Delta(9)-tetrahydrocannabinol and cannabidiol alone and in combination in frequent and infrequent cannabis users: acute intoxication effects","volume":"269","year":"2019","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"2026031204550967000_2026.03.05.709920v1.41","doi-asserted-by":"crossref","unstructured":"de Aquino PEA , Junior FJG , de Souza Nascimento T , Rosal Lustosa I , de Andrade GM , Ricardo N , et al. Nanoemulsions of Cannabidiol, Delta9-Tetrahydrocannabinol, and Their Combination Similarly Exerted Anticonvulsant and Antioxidant Effects in Mice Treated with Pentylenetetrazole. Pharmaceuticals (Basel). 2025;18(6).","DOI":"10.3390\/ph18060782"},{"key":"2026031204550967000_2026.03.05.709920v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpet.2025.103625"},{"key":"2026031204550967000_2026.03.05.709920v1.43","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2010.58"},{"key":"2026031204550967000_2026.03.05.709920v1.44","doi-asserted-by":"crossref","unstructured":"Andre CM , Hausman JF , Guerriero G . Cannabis sativa: The Plant of the Thousand and One Molecules. Front Plant Sci. 2016;7:19.","DOI":"10.3389\/fpls.2016.00019"},{"key":"2026031204550967000_2026.03.05.709920v1.45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0050269"},{"issue":"2","key":"2026031204550967000_2026.03.05.709920v1.46","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/S0022-3565(25)12911-X","article-title":"In vivo characterization of a specific cannabinoid receptor antagonist (SR141716A): inhibition of delta 9-tetrahydrocannabinol-induced responses and apparent agonist activity","volume":"277","year":"1996","journal-title":"J Pharmacol Exp Ther"},{"key":"2026031204550967000_2026.03.05.709920v1.47","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.58.4.322"},{"key":"2026031204550967000_2026.03.05.709920v1.48","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5400.401"},{"key":"2026031204550967000_2026.03.05.709920v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)00773-X"},{"key":"2026031204550967000_2026.03.05.709920v1.50","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14958"},{"key":"2026031204550967000_2026.03.05.709920v1.51","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707399"},{"key":"2026031204550967000_2026.03.05.709920v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(02)02624-9"},{"key":"2026031204550967000_2026.03.05.709920v1.53","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707133"},{"key":"2026031204550967000_2026.03.05.709920v1.54","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13250"},{"issue":"6","key":"2026031204550967000_2026.03.05.709920v1.55","doi-asserted-by":"crossref","first-page":"e00682","DOI":"10.1002\/prp2.682","article-title":"Diversity of molecular targets and signaling pathways for CBD","volume":"8","year":"2020","journal-title":"Pharmacol Res Perspect"},{"key":"2026031204550967000_2026.03.05.709920v1.56","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707442"},{"key":"2026031204550967000_2026.03.05.709920v1.57","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704327"},{"key":"2026031204550967000_2026.03.05.709920v1.58","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0284-z"},{"key":"2026031204550967000_2026.03.05.709920v1.59","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.115"},{"key":"2026031204550967000_2026.03.05.709920v1.60","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-005-6978-1"},{"key":"2026031204550967000_2026.03.05.709920v1.61","first-page":"61","article-title":"Molecular Pharmacology of Phytocannabinoids","volume":"103","year":"2017","journal-title":"Prog Chem Org Nat Prod"},{"key":"2026031204550967000_2026.03.05.709920v1.62","doi-asserted-by":"crossref","unstructured":"Parks C , Jones BC , Moore 2nd BM, Mulligan MK. Sex and strain variation in initial sensitivity and rapid tolerance to \u03949\u2013tetrahydrocannabinol. Cannabis and Canabinoid Research. 2020;in press.","DOI":"10.1089\/can.2019.0047"},{"key":"2026031204550967000_2026.03.05.709920v1.63","doi-asserted-by":"crossref","first-page":"659012","DOI":"10.3389\/fgene.2021.659012","article-title":"Genetic Modulation of Initial Sensitivity to Delta9-Tetrahydrocannabinol (THC) Among the BXD Family of Mice","volume":"12","year":"2021","journal-title":"Front Genet"},{"key":"2026031204550967000_2026.03.05.709920v1.64","doi-asserted-by":"crossref","first-page":"15251","DOI":"10.3389\/abp.2025.15251","article-title":"Molecular targets of cannabinoids and their derivatives in epilepsy - a review with focus on CBD","volume":"72","year":"2025","journal-title":"Acta Biochim Pol"},{"key":"2026031204550967000_2026.03.05.709920v1.65","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-011-2415-0"},{"key":"2026031204550967000_2026.03.05.709920v1.66","doi-asserted-by":"crossref","unstructured":"Dumbraveanu C , Strommer K , Wonnemann M , Choconta JL , Neumann A , Kress M , et al. Pharmacokinetics of Orally Applied Cannabinoids and Medical Marijuana Extracts in Mouse Nervous Tissue and Plasma: Relevance for Pain Treatment. Pharmaceutics. 2023;15(3).","DOI":"10.3390\/pharmaceutics15030853"},{"key":"2026031204550967000_2026.03.05.709920v1.67","doi-asserted-by":"crossref","unstructured":"Ferreira LF , Pathapati N , Schultz ST , Nunn MC , Pierce BL , Sanchez YR , et al. Acute cannabidiol treatment enhances social interaction in adult male mice. Adv Drug Alcohol Res. 2023;3.","DOI":"10.3389\/adar.2023.11163"},{"issue":"1","key":"2026031204550967000_2026.03.05.709920v1.68","doi-asserted-by":"crossref","first-page":"e0262633","DOI":"10.1371\/journal.pone.0262633","article-title":"Short communication: Tissue distribution of major cannabinoids following intraperitoneal injection in male rats","volume":"17","year":"2022","journal-title":"PLoS One"},{"key":"2026031204550967000_2026.03.05.709920v1.69","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-015-0377-3"},{"key":"2026031204550967000_2026.03.05.709920v1.70","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.160"},{"issue":"2","key":"2026031204550967000_2026.03.05.709920v1.71","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.tips.2024.12.005","article-title":"Therapeutic potential of cannabidiol polypharmacology in neuropsychiatric disorders","volume":"46","year":"2025","journal-title":"Trends Pharmacol Sci"},{"key":"2026031204550967000_2026.03.05.709920v1.72","doi-asserted-by":"crossref","first-page":"116191","DOI":"10.1016\/j.bcp.2024.116191","article-title":"CYP2C9, CYP3A and CYP2C19 metabolize Delta9-tetrahydrocannabinol to multiple metabolites but metabolism is affected by human liver fatty acid binding protein (FABP1)","volume":"228","year":"2024","journal-title":"Biochem Pharmacol"},{"key":"2026031204550967000_2026.03.05.709920v1.73","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.120.000350"},{"issue":"2","key":"2026031204550967000_2026.03.05.709920v1.74","doi-asserted-by":"crossref","first-page":"100037","DOI":"10.1016\/j.dmd.2025.100037","article-title":"Cannabidiol and Delta9-tetrahydrocannabinol induce drug-metabolizing enzymes, but not transporters, in human hepatocytes: Implications for predicting complex cannabinoid-drug interactions","volume":"53","year":"2025","journal-title":"Drug Metab Dispos"},{"key":"2026031204550967000_2026.03.05.709920v1.75","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-6427-7_4"},{"issue":"3","key":"2026031204550967000_2026.03.05.709920v1.76","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.cels.2020.12.002","article-title":"A platform for experimental precision medicine: The extended BXD mouse family","volume":"12","year":"2021","journal-title":"Cell Syst"},{"key":"2026031204550967000_2026.03.05.709920v1.77","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1972.tb08092.x"},{"issue":"8","key":"2026031204550967000_2026.03.05.709920v1.78","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/S0090-9556(25)06664-4","article-title":"Effect of cannabidiol pretreatment on the kinetics of tetrahydrocannabinol metabolites in mouse brain","volume":"23","year":"1995","journal-title":"Drug Metab Dispos"},{"key":"2026031204550967000_2026.03.05.709920v1.79","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(01)00616-5"},{"key":"2026031204550967000_2026.03.05.709920v1.80","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-006-0356-9"},{"key":"2026031204550967000_2026.03.05.709920v1.81","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.19.1109"},{"key":"2026031204550967000_2026.03.05.709920v1.82","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705920"},{"key":"2026031204550967000_2026.03.05.709920v1.83","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.09.090"},{"key":"2026031204550967000_2026.03.05.709920v1.84","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13333"},{"key":"2026031204550967000_2026.03.05.709920v1.85","doi-asserted-by":"crossref","unstructured":"Kasten CR , Zhang Y , Boehm SL , 2nd. Acute Cannabinoids Produce Robust Anxiety-Like and Locomotor Effects in Mice, but Long-Term Consequences Are Age- and Sex-Dependent. Front Behav Neurosci. 2019;13:32.","DOI":"10.3389\/fnbeh.2019.00032"},{"key":"2026031204550967000_2026.03.05.709920v1.86","doi-asserted-by":"crossref","unstructured":"De Giacomo V , Ruehle S , Lutz B , Haring M , Remmers F . Differential glutamatergic and GABAergic contributions to the tetrad effects of Delta(9)-tetrahydrocannabinol revealed by cell-type-specific reconstitution of the CB1 receptor. Neuropharmacology. 2020;179:108287.","DOI":"10.1016\/j.neuropharm.2020.108287"},{"issue":"2","key":"2026031204550967000_2026.03.05.709920v1.87","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/j.1476-5381.1982.tb08802.x","article-title":"Changes in body temperature and oxygen consumption rate of conscious mice produced by intrahypothalamic and intracerebroventricular injections of delta 9-tetrahydrocannabinol","volume":"75","year":"1982","journal-title":"British journal of pharmacology"},{"key":"2026031204550967000_2026.03.05.709920v1.88","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.301.3.963"},{"issue":"1","key":"2026031204550967000_2026.03.05.709920v1.89","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.pbb.2004.02.006","article-title":"GABAA receptors modulate cannabinoid-evoked hypothermia","volume":"78","year":"2004","journal-title":"Pharmacol Biochem Behav"},{"key":"2026031204550967000_2026.03.05.709920v1.90","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.037473"},{"key":"2026031204550967000_2026.03.05.709920v1.91","doi-asserted-by":"crossref","unstructured":"Blazquez C , Ruiz-Calvo A , Bajo-Graneras R , Baufreton JM , Resel E , Varilh M , et al. Inhibition of striatonigral autophagy as a link between cannabinoid intoxication and impairment of motor coordination. Elife. 2020;9.","DOI":"10.7554\/eLife.56811"},{"key":"2026031204550967000_2026.03.05.709920v1.92","doi-asserted-by":"publisher","DOI":"10.1101\/gad.260869.115"},{"key":"2026031204550967000_2026.03.05.709920v1.93","doi-asserted-by":"crossref","first-page":"107568","DOI":"10.1016\/j.neuropharm.2019.03.011","article-title":"Identification of potassium channel proteins Kv7.2\/7.3 as common partners of the dopamine and glutamate transporters DAT and GLT-1","volume":"161","year":"2019","journal-title":"Neuropharmacology"},{"key":"2026031204550967000_2026.03.05.709920v1.94","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3143-03.2004"},{"key":"2026031204550967000_2026.03.05.709920v1.95","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04266-w"},{"key":"2026031204550967000_2026.03.05.709920v1.96","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1381-05.2005"},{"key":"2026031204550967000_2026.03.05.709920v1.97","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19990920)412:2<342::AID-CNE11>3.0.CO;2-2"},{"key":"2026031204550967000_2026.03.05.709920v1.98","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2018.03.011"},{"issue":"2","key":"2026031204550967000_2026.03.05.709920v1.99","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s10571-022-01211-w","article-title":"Structure and Function of Sodium Channel Nav1.3 in Neurological Disorders","volume":"43","year":"2023","journal-title":"Cell Mol Neurobiol"},{"key":"2026031204550967000_2026.03.05.709920v1.100","doi-asserted-by":"crossref","first-page":"188","DOI":"10.3389\/fgene.2019.00188","article-title":"Identification of a Functional Non-coding Variant in the GABA (A) Receptor alpha2 Subunit of the C57BL\/6J Mouse Reference Genome: Major Implications for Neuroscience Research","volume":"10","year":"2019","journal-title":"Front Genet"},{"key":"2026031204550967000_2026.03.05.709920v1.101","doi-asserted-by":"publisher","DOI":"10.1111\/gbb.12774"},{"issue":"1","key":"2026031204550967000_2026.03.05.709920v1.102","doi-asserted-by":"crossref","first-page":"e70009","DOI":"10.1111\/gbb.70009","article-title":"Atp1a2 and Kcnj9 Are Candidate Genes Underlying Sensitivity to Oxycodone-Induced Locomotor Activation and Withdrawal-Induced Anxiety-Like Behaviors in C57BL\/6 Substrains","volume":"24","year":"2025","journal-title":"Genes Brain Behav"},{"key":"2026031204550967000_2026.03.05.709920v1.103","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-021-09877-1"},{"key":"2026031204550967000_2026.03.05.709920v1.104","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.162594"},{"key":"2026031204550967000_2026.03.05.709920v1.105","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16183"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.03.05.709920","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T11:55:47Z","timestamp":1773316547000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.03.05.709920"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,9]]},"references-count":105,"URL":"https:\/\/doi.org\/10.64898\/2026.03.05.709920","relation":{},"subject":[],"published":{"date-parts":[[2026,3,9]]},"subtype":"preprint"}}