{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:41:44Z","timestamp":1785890504059,"version":"3.56.0"},"reference-count":117,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cannabinoids are active substances present in plants of the Cannabis genus. Both the Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved several medicinal products containing natural cannabinoids or their synthetic derivatives for the treatment of drug-resistant epilepsy, nausea and vomiting associated with cancer chemotherapy, anorexia in AIDS patients, and the alleviation of symptoms in patients with multiple sclerosis. In fact, cannabinoids constitute a broad group of molecules with a possible therapeutic potential that could be used in the management of much more diseases than mentioned above; therefore, multiple preclinical and clinical studies on cannabinoids have been carried out in recent years. Danio rerio (zebrafish) is an animal model that has gained more attention lately due to its numerous advantages, including easy and fast reproduction, the significant similarity of the zebrafish genome to the human one, simplicity of genetic modifications, and body transparency during the early stages of development. A number of studies have confirmed the usefulness of this model in toxicological research, experiments related to the impact of early life exposure to xenobiotics, modeling various diseases, and screening tests to detect active substances with promising biological activity. The present paper focuses on the current knowledge of the endocannabinoid system in the zebrafish model, and it summarizes the results and observations from studies investigating the pharmacological effects of natural and synthetic cannabinoids that were carried out in Danio rerio. The presented data support the notion that the zebrafish model is a suitable animal model for use in cannabinoid research.<\/jats:p>","DOI":"10.3390\/ijms241310455","type":"journal-article","created":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T01:49:32Z","timestamp":1687398572000},"page":"10455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Zebrafish as an Animal Model in Cannabinoid Research"],"prefix":"10.3390","volume":"24","author":[{"given":"Joanna","family":"Lachowicz","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmaceutical Care, Medical University of Lublin, 1 Chod\u017aki Street, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7756-2904","authenticated-orcid":false,"given":"Aleksandra","family":"Szopa","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmaceutical Care, Medical University of Lublin, 1 Chod\u017aki Street, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Ignatiuk","sequence":"additional","affiliation":[{"name":"Scientific Circle, Department of Clincal Pharmacy and Pharmaceutical Care, Medical University of Lublin, 1 Chod\u017aki Street, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"\u015awi\u0105der","sequence":"additional","affiliation":[{"name":"Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, 1 Chod\u017aki Street, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5732-8950","authenticated-orcid":false,"given":"Anna","family":"Serefko","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmaceutical Care, Medical University of Lublin, 1 Chod\u017aki Street, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1590\/S1516-44462006000200015","article-title":"History of cannabis as a medicine: A review","volume":"28","author":"Zuardi","year":"2006","journal-title":"Braz. J. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8342","DOI":"10.1002\/jcp.27725","article-title":"Medical Cannabis: A plurimillennial history of an evergreen","volume":"234","author":"Pisanti","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_3","first-page":"1","article-title":"Phytochemistry of Cannabis sativa L.","volume":"103","author":"ElSohly","year":"2017","journal-title":"Prog. Chem. Org. Nat. Prod."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1055\/s-0031-1298334","article-title":"Heat exposure of Cannabis sativa extracts affects the pharmacokinetic and metabolic profile in healthy male subjects","volume":"78","author":"Eichler","year":"2012","journal-title":"Planta Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1111\/bcp.13710","article-title":"The pharmacokinetics and the pharmacodynamics of cannabinoids","volume":"84","author":"Lucas","year":"2018","journal-title":"Br. J. Clin. Pharm."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.yebeh.2016.11.016","article-title":"Pharmacology of cannabinoids in the treatment of epilepsy","volume":"70 Pt. B","author":"Gaston","year":"2017","journal-title":"Epilepsy Behav."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2165\/00003088-200342040-00003","article-title":"Pharmacokinetics and pharmacodynamics of cannabinoids","volume":"42","author":"Grotenhermen","year":"2003","journal-title":"Clin. Pharmacokinet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1002\/jps.20036","article-title":"In vitro\/in vivo correlation studies for transdermal delta 8-THC development","volume":"93","author":"Valiveti","year":"2004","journal-title":"J. Pharm. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1080\/10408347.2020.1864718","article-title":"Cannabinoids: Recent Updates on Public Perception, Adverse Reactions, Pharmacokinetics, Pretreatment Methods and Their Analysis Methods","volume":"52","author":"Li","year":"2022","journal-title":"Crit. Rev. Anal. Chem."},{"key":"ref_10","first-page":"149","article-title":"Chemistry, metabolism, and toxicology of cannabis: Clinical implications","volume":"7","author":"Sharma","year":"2012","journal-title":"Iran. J. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2174\/157015907780866884","article-title":"The cannabinoid CB2 receptor as a target for inflammation-dependent neurodegeneration","volume":"5","author":"Ashton","year":"2007","journal-title":"Curr. Neuropharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1517\/17460440903018857","article-title":"Fatty acid amide hydrolase as a potential therapeutic target for the treatment of pain and CNS disorders","volume":"4","author":"Ahn","year":"2009","journal-title":"Expert Opin. Drug. Discov."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.apsb.2019.10.006","article-title":"Monoacylglycerol lipase inhibitors: Modulators for lipid metabolism in cancer malignancy, neurological and metabolic disorders","volume":"10","author":"Deng","year":"2020","journal-title":"Acta Pharm. Sin."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/s41401-018-0164-x","article-title":"Translational potential of allosteric modulators targeting the cannabinoid CB1 receptor","volume":"40","author":"Lu","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1146\/annurev.neuro.29.051605.112834","article-title":"Endocannabinoid-mediated synaptic plasticity in the CNS","volume":"29","author":"Chevaleyre","year":"2006","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/3-540-26573-2_9","article-title":"The phylogenetic distribution and evolutionary origins of endocannabinoid signalling","volume":"168","author":"Elphick","year":"2005","journal-title":"Handb. Exp. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1177\/1073858410397377","article-title":"Endocannabinoids and retrograde modulation of synaptic transmission","volume":"18","author":"Tanimura","year":"2012","journal-title":"Neuroscientist"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/dgd.12351","article-title":"Role of the endocannabinoid system in vertebrates: Emphasis on the zebrafish model","volume":"59","author":"Oltrabella","year":"2017","journal-title":"Dev. Growth Differ."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.cmet.2013.03.001","article-title":"The endocannabinoid system in energy homeostasis and the etiopathology of metabolic disorders","volume":"17","author":"Silvestri","year":"2013","journal-title":"Cell Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.2174\/092986710790980023","article-title":"CB1 cannabinoid receptors and their associated proteins","volume":"17","author":"Howlett","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1590\/S0004-27302006000200025","article-title":"The endocannabinoid system: A new paradigm in the metabolic syndrome treatment","volume":"50","author":"Guedes","year":"2006","journal-title":"Arq. Bras. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Licitra, R., Martinelli, M., Petrocchi Jasinski, L., Marchese, M., Kiferle, C., and Fronte, B. (2021). In vivo evaluation of Cannabis sativa full extract on zebrafish larvae development, locomotion behavior and gene expression. Pharmaceuticals, 14.","DOI":"10.3390\/ph14121224"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/bs.apha.2017.03.007","article-title":"CB1 and CB2 Receptor Pharmacology","volume":"80","author":"Howlett","year":"2017","journal-title":"Adv. Pharm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/nrn3876","article-title":"Endocannabinoid signalling and the deteriorating brain","volume":"16","author":"Stella","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.gene.2015.07.036","article-title":"Elucidating cannabinoid biology in zebrafish (Danio rerio)","volume":"570","author":"Krug","year":"2015","journal-title":"Gene"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11515","DOI":"10.1038\/s41598-021-90902-3","article-title":"Medium-throughput zebrafish optogenetic platform identifies deficits in subsequent neural activity following brief early exposure to cannabidiol and \u03949-tetrahydrocannabinol","volume":"11","author":"Kanyo","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.pbb.2015.06.008","article-title":"Caffeine protects against memory loss induced by high and non-anxiolytic dose of cannabidiol in adult zebrafish (Danio rerio)","volume":"135","author":"Nazario","year":"2015","journal-title":"Pharm. Biochem. Behav."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Zou, S., and Kumar, U. (2018). Cannabinoid receptors and the endocannabinoid system: Signaling and function in the central nervous system. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030833"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4112","DOI":"10.2174\/13816128113199990620","article-title":"Acute and long-term effects of cannabis use: A review","volume":"20","author":"Karila","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.ejim.2018.01.001","article-title":"Medical use of cannabis and cannabinoids containing products\u2014Regulations in Europe and North America","volume":"49","author":"Abuhasira","year":"2018","journal-title":"Eur. J. Intern. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s13311-015-0375-5","article-title":"Cannabinoids and Epilepsy","volume":"12","author":"Rosenberg","year":"2015","journal-title":"Neurotherapeutics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1007\/s00432-021-03710-7","article-title":"Cannabinoids in the landscape of cancer","volume":"147","author":"Mangal","year":"2021","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.phrs.2016.01.033","article-title":"Cannabidiol, neuroprotection and neuropsychiatric disorders","volume":"112","author":"Campos","year":"2016","journal-title":"Pharm. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.tips.2016.04.005","article-title":"Beyond Cannabis: Plants and the endocannabinoid system","volume":"37","author":"Russo","year":"2016","journal-title":"Trends Pharm. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1097\/j.pain.0000000000002268","article-title":"Cannabinoids, the endocannabinoid system, and pain: A review of preclinical studies","volume":"162","author":"Finn","year":"2021","journal-title":"Pain"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1097\/FBP.0000000000000665","article-title":"Evidence for spontaneous cannabinoid withdrawal in mice","volume":"33","author":"Paronis","year":"2022","journal-title":"Behav. Pharm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1093\/af\/vfz020","article-title":"The use of zebrafish (Danio rerio) as biomedical models","volume":"9","author":"Teame","year":"2019","journal-title":"Anim. Front."},{"key":"ref_38","first-page":"e-70884","article-title":"Zebrafish (Danio rerio) meets bioethics: The 10Rs ethical principles in research","volume":"23","author":"Canedo","year":"2022","journal-title":"Vet. Med. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.chemosphere.2018.04.078","article-title":"Role of Bisphenol A on the Endocannabinoid System at central and peripheral levels: Effects on adult female zebrafish","volume":"205","author":"Santangeli","year":"2018","journal-title":"Chemospher"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"464","DOI":"10.3389\/fphar.2020.00464","article-title":"Phenotype-based screening of synthetic cannabinoids in a dravet syndrome zebrafish model","volume":"11","author":"Griffin","year":"2020","journal-title":"Front. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.neuroscience.2005.10.069","article-title":"Distribution of cannabinoid receptor 1 in the CNS of zebrafish","volume":"138","author":"Lam","year":"2006","journal-title":"Neuroscience"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e0022","DOI":"10.5041\/RMMJ.10129","article-title":"The endocannabinoid system, cannabinoids, and pain","volume":"4","author":"Fine","year":"2013","journal-title":"Rambam Maimonides Med. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.1365-2826.2008.01670.x","article-title":"Multiple roles for the endocannabinoid system during the earliest stages of life: Pre- and postnatal development","volume":"20","author":"Fride","year":"2008","journal-title":"J. Neuroendocr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.mce.2008.11.014","article-title":"A novel role for the endocannabinoid system during zebrafish development","volume":"299","author":"Migliarini","year":"2009","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"jeb206680","DOI":"10.1242\/jeb.206680","article-title":"CB1 and CB2 receptors play differential roles in early zebrafish locomotor development","volume":"222 Pt. 16","author":"Sufian","year":"2019","journal-title":"J. Exp. Biol."},{"key":"ref_46","first-page":"236063","article-title":"Endocannabinoids in zebrafish are necessary for normal development and locomotion","volume":"7","author":"Sufian","year":"2018","journal-title":"J. Drug Alcohol Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.bbr.2015.04.046","article-title":"The endocannabinoid system and associative learning and memory in zebrafish","volume":"290","author":"Ruhl","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.mcn.2008.02.001","article-title":"The endocannabinoid receptor, CB1, is required for normal axonal growth and fasciculation","volume":"38","author":"Watson","year":"2008","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.gene.2006.09.016","article-title":"Characterization of two duplicate zebrafish Cb2-like cannabinoid receptors","volume":"389","author":"Rodriguez","year":"2007","journal-title":"Gene"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1089\/can.2018.0025","article-title":"Altered swimming behaviors in zebrafish larvae lacking cannabinoid receptor 2","volume":"4","author":"Varshney","year":"2019","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1242\/dev.121731","article-title":"Cannabinoid receptor signaling regulates liver development and metabolism","volume":"143","author":"Liu","year":"2016","journal-title":"Development"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Krug, R.G., Lee, H.B., El Khoury, L.Y., Sigafoos, A.N., Petersen, M.O., and Clark, K.J. (2018). The endocannabinoid gene faah2a modulates stress-associated behavior in zebrafish. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0190897"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/s41390-020-01332-2","article-title":"Cannabis use and measurement of cannabinoids in plasma and breast milk of breastfeeding mothers","volume":"90","author":"Moss","year":"2021","journal-title":"Pediatr. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1001\/jama.2016.17383","article-title":"Trends in marijuana use among pregnant and nonpregnant reproductive-aged women, 2002\u20132014","volume":"317","author":"Brown","year":"2017","journal-title":"JAMA"},{"key":"ref_55","first-page":"33","article-title":"Long-term effects of cannabinoids on development\/behaviour","volume":"22","author":"Lagae","year":"2020","journal-title":"Epileptic Disord."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ypmed.2018.08.036","article-title":"An epidemiological, developmental and clinical overview of cannabis use during pregnancy","volume":"116","author":"Brown","year":"2018","journal-title":"Prev. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1093\/toxsci\/kfy044","article-title":"Making waves: New developments in toxicology with the zebrafish","volume":"163","author":"Horzmann","year":"2018","journal-title":"Toxicol. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"16057","DOI":"10.1038\/s41598-019-52336-w","article-title":"Cannabinoids exacerbate alcohol teratogenesis by a CB1-hedgehog interaction","volume":"9","author":"Fish","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1002\/bdr2.1458","article-title":"Ethanol and cannabinoids interact to alter behavior in a zebrafish fetal alcohol spectrum disorder model","volume":"111","author":"Zhang","year":"2019","journal-title":"Birth Defects Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10518","DOI":"10.1038\/s41598-018-28689-z","article-title":"Motor neuron development in zebrafish is altered by brief (5-hr) exposures to THC (\u22069-tetrahydrocannabinol) or CBD (cannabidiol) during gastrulation","volume":"8","author":"Ahmed","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Amin, M.R., Ahmed, K.T., and Ali, D.W. (2020). Early Exposure to THC alters M-cell development in zebrafish embryos. Biomedicines, 8.","DOI":"10.3390\/biomedicines8010005"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1093\/toxsci\/kfx232","article-title":"Developmental effects of cannabidiol and \u03949-tetrahydrocannabinol in zebrafish","volume":"162","author":"Carty","year":"2018","journal-title":"Toxicol. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"126417","DOI":"10.1016\/j.chemosphere.2020.126417","article-title":"Cannabinol in the spotlight: Toxicometabolomic study and behavioral analysis of zebrafish embryos exposed to the unknown cannabinoid","volume":"252","author":"Chousidis","year":"2020","journal-title":"Chemosphere"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Chatzimitakos, T., Chousidis, I., Leonardos, D., Stalikas, C., and Leonardos, I. (2022). In the swim of Cannabis: Developmental toxicity and metabolomic pathway alterations of zebrafish larvae exposed to THC for the assessment of its potential environmental and human health impact. Molecules, 27.","DOI":"10.3390\/molecules27175506"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"109000","DOI":"10.1016\/j.cbpc.2021.109000","article-title":"Short- and long-term exposures of the synthetic cannabinoid 5F-APINAC induce metabolomic alterations associated with neurotransmitter systems and embryotoxicity confirmed by teratogenicity in zebrafish","volume":"243","author":"Markin","year":"2021","journal-title":"Comp. Biochem. Physiol. C Toxicol. Pharm."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"20251","DOI":"10.1038\/s41598-022-23495-0","article-title":"Cannabinoid receptor 2 (Cb2r) mediates cannabinol (CBN) induced developmental defects in zebrafish","volume":"12","author":"Amin","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.taap.2018.12.021","article-title":"Multigenerational consequences of early-life cannabinoid exposure in zebrafish","volume":"364","author":"Carty","year":"2019","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1007\/s11357-020-00182-4","article-title":"Developmental exposure to cannabidiol (CBD) alters longevity and health span of zebrafish (Danio rerio)","volume":"42","author":"Pandelides","year":"2020","journal-title":"Geroscience"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Basnet, R.M., Zizioli, D., Taweedet, S., Finazzi, D., and Memo, M. (2019). Zebrafish larvae as a behavioral model in neuropharmacology. Biomedicines, 7.","DOI":"10.3390\/biomedicines7010023"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1002\/etc.4951","article-title":"Approaches to test the neurotoxicity of environmental contaminants in the zebrafish model: From behavior to molecular mechanisms","volume":"40","author":"Fitzgerald","year":"2021","journal-title":"Env. Toxicol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Lachowicz, J., Niedzia\u0142ek, K., Rostkowska, E., Szopa, A., \u015awi\u0105der, K., Szponar, J., and Serefko, A. (2021). Zebrafish as an animal model for testing agents with antidepressant potential. Life, 11.","DOI":"10.3390\/life11080792"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/s13311-015-0387-1","article-title":"Cannabidiol as a potential treatment for anxiety disorders","volume":"12","author":"Blessing","year":"2015","journal-title":"Neurotherapeutics"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1186\/s12967-020-02518-2","article-title":"Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties","volume":"18","author":"Sharpe","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/S2215-0366(19)30401-8","article-title":"Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: A systematic review and meta-analysis","volume":"6","author":"Black","year":"2019","journal-title":"Lanc. Psychiatry"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jpain.2007.09.002","article-title":"Ethans nabilone for the treatment of pain in fibromyalgia","volume":"9","author":"Skrabek","year":"2008","journal-title":"J. Pain."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1111\/j.1460-9568.2007.05476.x","article-title":"Correlated species differences in the effects of cannabinoid ligands on anxiety and on GABAergic and glutamatergic synaptic transmission","volume":"25","author":"Haller","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.neuropharm.2009.07.014","article-title":"Bidirectional regulation of novelty-induced behavioral inhibition by the endocannabinoid system","volume":"57","author":"Chaouloff","year":"2009","journal-title":"Neuropharmacology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1007\/s40261-022-01205-y","article-title":"Effects of cannabidiol on appetite and body weight: A systematic review","volume":"42","author":"Pinto","year":"2022","journal-title":"Clin. Drug Investig."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1111\/acer.14383","article-title":"Ethanol and cannabinoids regulate zebrafish GABAergic neuron development and behavior in a sonic hedgehog and fibroblast growth factor-dependent mechanism","volume":"44","author":"Zhang","year":"2020","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Jensen, H.M., Korbut, R., Kania, P.W., and Buchmann, K. (2018). Cannabidiol effects on behaviour and immune gene expression in zebrafish (Danio rerio). PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0200016"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Hasumi, A., Maeda, H., and Yoshida, K.I. (2020). Analyzing cannabinoid-induced abnormal behavior in a zebrafish model. PLoS ONE, 15.","DOI":"10.1101\/2020.07.13.200428"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Gonz\u00e1lez, J., de Quadros, B., Havelange, W., Brock, A.J., and Brennan, C.H. (2021). Behavioral effects of developmental exposure to JWH-018 in wild-type and disrupted in schizophrenia 1 (disc1) mutant zebrafish. Biomolecules, 11.","DOI":"10.3390\/biom11020319"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s42238-021-00103-y","article-title":"Assessing the bioactivity of cannabis extracts in larval zebrafish","volume":"3","author":"Nixon","year":"2021","journal-title":"J. Cannabis Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"598812","DOI":"10.3389\/fnbeh.2020.598812","article-title":"Putative activation of the CB1 cannabinoid receptors prevents anxiety-like behavior, oxidative stress, and GABA decrease in the brain of zebrafish submitted to acute restraint stress","volume":"14","author":"Cardoso","year":"2021","journal-title":"Front. Behav. Neurosci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"15693","DOI":"10.1038\/s41598-021-95016-4","article-title":"THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior","volume":"11","author":"Zarei","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1089\/zeb.2017.1541","article-title":"Analysis of the uptake, metabolism, and behavioral effects of cannabinoids on zebrafish larvae","volume":"15","author":"Achenbach","year":"2018","journal-title":"Zebrafish"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3553","DOI":"10.1080\/14786419.2020.1869230","article-title":"9,10-Dihydro-5-hydroxy-2,3,6-trimethoxyphenanthrene-1,4-dione: A new dihydrophenanthrene from commercial cannabis and its effect on zebrafish larval behaviour","volume":"36","author":"Banskota","year":"2022","journal-title":"Nat. Prod. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/s41573-021-00210-8","article-title":"Zebrafish disease models in drug discovery: From preclinical modelling to clinical trials","volume":"20","author":"Patton","year":"2021","journal-title":"Nat. Rev. Drug. Discov."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Park, Y.M., Dahlem, C., Meyer, M.R., Kiemer, A.K., M\u00fcller, R., and Herrmann, J. (2022). Induction of liver size reduction in zebrafish larvae by the emerging synthetic cannabinoid 4F-MDMB-BINACA and its impact on drug metabolism. Molecules, 27.","DOI":"10.3390\/molecules27041290"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1002\/dta.3195","article-title":"Metabolism of third generation synthetic cannabinoids using zebrafish larvae","volume":"14","author":"Armenta","year":"2022","journal-title":"Drug. Test. Anal."},{"key":"ref_91","unstructured":"United Nations Organizations (2022, November 09). Drug and Crime Office. Global Synthetic Drugs Assessment. Available online: https:\/\/www.unodc.org\/documents\/scientific\/Global_Synthetic_Drugs_Assessment_2020.pdf."},{"key":"ref_92","first-page":"1","article-title":"The Cannabinoids International Experts Panel; Collaborators. Epilepsy and cannabidiol: A guide to treatment","volume":"22","author":"Arzimanoglou","year":"2020","journal-title":"Epileptic Disord"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ejpn.2020.01.006","article-title":"Imaging epilepsy in larval zebrafish","volume":"24","author":"Burrows","year":"2020","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neubiorev.2020.06.010","article-title":"Seizing the moment: Zebrafish epilepsy models","volume":"116","author":"Gawel","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"7243","DOI":"10.1111\/febs.15694","article-title":"Past, present and future of zebrafish in epilepsy research","volume":"288","author":"Yaksi","year":"2021","journal-title":"FEBS J."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Prakash, S., and Carter, W.G. (2021). The neuroprotective effects of cannabis-derived phytocannabinoids and resveratrol in Parkinson\u2019s disease: A systematic literature review of pre-clinical studies. Brain Sci., 11.","DOI":"10.20944\/preprints202111.0050.v1"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"595635","DOI":"10.3389\/fphar.2020.595635","article-title":"Cannabidiol as a therapeutic target: Evidence of its neuroprotective and neuromodulatory function in Parkinson\u2019s disease","volume":"11","author":"Patricio","year":"2020","journal-title":"Front. Pharm."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"109745","DOI":"10.1016\/j.pnpbp.2019.109745","article-title":"The therapeutic role of cannabinoid receptors and its agonists or antagonists in Parkinson\u2019s disease","volume":"96","author":"Han","year":"2020","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Chia, S.J., Tan, E.K., and Chao, Y.X. (2020). Historical perspective: Models of Parkinson\u2019s disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072464"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"835827","DOI":"10.3389\/fphar.2022.835827","article-title":"A Critical review of zebrafish models of Parkinson\u2019s disease","volume":"13","author":"Doyle","year":"2022","journal-title":"Front. Pharm."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/s11910-011-0182-2","article-title":"Modeling neurodegeneration in zebrafish","volume":"11","author":"Xi","year":"2011","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/978-3-030-21737-2_4","article-title":"Cannabinoid signaling in cancer","volume":"1162","author":"Das","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1093\/jncimonographs\/lgab008","article-title":"Cannabinoid cancer biology and prevention","volume":"2021","author":"McAllister","year":"2021","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"179","DOI":"10.46747\/cfp.6803179","article-title":"PEER simplified chronic pain guideline: Management of chronic low back, osteoarthritic, and neuropathic pain in primary care","volume":"68","author":"Korownyk","year":"2022","journal-title":"Can. Fam. Physician"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1097\/SPC.0000000000000493","article-title":"Cannabis and cannabinoids in cancer pain management","volume":"14","author":"Meng","year":"2020","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.bbr.2017.09.028","article-title":"Comparison of cannabinoids with known analgesics using a novel high throughput zebrafish larval model of nociception","volume":"337","author":"Ellis","year":"2018","journal-title":"Behav. Brain Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"907579","DOI":"10.3389\/fphar.2022.907579","article-title":"Identification of minimum essential therapeutic mixtures from cannabis plant extracts by screening in cell and animal models of Parkinson\u2019s disease","volume":"13","author":"Morash","year":"2022","journal-title":"Front. Pharm."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"104694","DOI":"10.1016\/j.jff.2021.104694","article-title":"Cannabidiol promotes fin regeneration and reduces apoptosis in zebrafish embryos","volume":"86","author":"Xu","year":"2021","journal-title":"J. Funct. Foods"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.bbr.2019.01.040","article-title":"Cannabidiol modulates phosphorylated rpS6 signalling in a zebrafish model of Tuberous Sclerosis Complex","volume":"363","author":"Serra","year":"2019","journal-title":"Behav. Brain Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"226","DOI":"10.3389\/fphar.2019.00226","article-title":"Single and synergistic effects of cannabidiol and \u0394-9-tetrahydrocannabinol on zebrafish models of neuro-hyperactivity","volume":"10","author":"Samarut","year":"2019","journal-title":"Front. Pharm."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.3389\/fphar.2019.01124","article-title":"Antitumor activity of abnormal cannabidiol and its analog O-1602 in taxol-resistant preclinical models of breast cancer","volume":"10","author":"Tomko","year":"2019","journal-title":"Front. Pharm."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"107152","DOI":"10.1016\/j.yebeh.2020.107152","article-title":"Cannabis constituents reduce seizure behavior in chemically-induced and scn1a-mutant zebrafish","volume":"110","author":"Thornton","year":"2020","journal-title":"Epilepsy Behav."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1159\/000521683","article-title":"Therapeutic potential of cannabis, cannabidiol, and cannabinoid-based pharmaceuticals","volume":"107","author":"Legare","year":"2022","journal-title":"Pharmacology"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Pagano, C., Navarra, G., Coppola, L., Avilia, G., Bifulco, M., and Laezza, C. (2022). Cannabinoids: Therapeutic use in clinical practice. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23063344"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Guti\u00e9rrez, M.S., Navarrete, F., Gasparyan, A., Austrich-Olivares, A., Sala, F., and Manzanares, J. (2020). Cannabidiol: A potential new alternative for the treatment of anxiety, depression, and psychotic disorders. Biomolecules, 10.","DOI":"10.3390\/biom10111575"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"597725","DOI":"10.3389\/fpsyt.2021.597725","article-title":"Cannabis use and mental illness: Understanding circuit dysfunction through preclinical models","volume":"12","author":"Jenkins","year":"2021","journal-title":"Front. Psychiatry"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/nrd4627","article-title":"Zebrafish as tools for drug discovery","volume":"14","author":"MacRae","year":"2015","journal-title":"Nat. Rev. Drug. Discov."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/10455\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:58:05Z","timestamp":1760126285000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/10455"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,21]]},"references-count":117,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241310455"],"URL":"https:\/\/doi.org\/10.3390\/ijms241310455","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,21]]}}}