{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:55:05Z","timestamp":1792788905552,"version":"4.5.0"},"reference-count":59,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFE0203900"],"award-info":[{"award-number":["2022YFE0203900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Agricultural Science and Technology Innovation Project","award":["T2023327"],"award-info":[{"award-number":["T2023327"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Intensive aquaculture induces severe environmental stress and disease susceptibility in Pacific white shrimp (Litopenaeus vannamei). Cannabidiol (CBD) offers significant potential as a bioactive stress-mitigating additive. This study evaluated the effects of dietary CBD supplementation (0, 10, 20, 40, and 80 mg\/kg) on the growth, intestinal microecology, and stress tolerance of juvenile L. vannamei over an 8-week feeding trial, followed by a combined chronic ammonia and acute hypoxia challenge. Moderate CBD supplementation (10\u201340 mg\/kg) significantly promoted growth, minimized feed conversion ratios, and enriched muscle eicosapentaenoic (EPA) and docosahexaenoic acids (DHA). Furthermore, CBD restructured the intestinal microbiota by suppressing opportunistic pathogens and enriching beneficial taxa. Under combined stress, moderate CBD prolonged the median lethal time (LT50) by up-regulating hypoxia-inducible factor 1-alpha (hif-1\u03b1) and heat shock protein 70 (hsp70) transcription and boosting systemic antioxidant capacity to neutralize lipid peroxidation. Conversely, the highest dose (80 mg\/kg) induced metabolic exhaustion and hepatopancreatic toxicity, evidenced by drastically elevated serum transaminases and diminished stress tolerance. Conclusively, dietary CBD exerts a classic biphasic effect in L. vannamei. Inclusion at 10\u201340 mg\/kg safely promotes the best comprehensive effects on growth, immune homeostasis, and environmental resilience within the concentration range tested in this study, whereas excessive administration provokes severe metabolic burden, highlighting the critical need for strict dosage regulation.<\/jats:p>","DOI":"10.3390\/antiox15040475","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T13:16:17Z","timestamp":1775826977000},"page":"475","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Moderate Dietary Cannabidiol Enhances Growth, Restructures Gut Microbiota, and Bolsters Environmental Stress Resilience in Litopenaeus vannamei"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5444-9060","authenticated-orcid":false,"given":"Jingwei","family":"Liu","sequence":"first","affiliation":[{"name":"China-ASEAN Belt and Road Joint Laboratory on Mariculture Technology (Shanghai), Shanghai Ocean University, Shanghai 201306, China"},{"name":"Centre for Research on Environmental Ecology and Fish Nutrition of the Ministry of Agriculture, Shanghai 201306, China"},{"name":"National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai 201306, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Lin","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of the Traditional Chinese Medicine Agricultural Biogenomics, Changsha Medical University, Changsha 410219, China"},{"name":"Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha 410205, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianchao","family":"Lu","sequence":"additional","affiliation":[{"name":"Centre for Research on Environmental Ecology and Fish Nutrition of the Ministry of Agriculture, Shanghai 201306, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianwei","family":"Jiang","sequence":"additional","affiliation":[{"name":"China-ASEAN Belt and Road Joint Laboratory on Mariculture Technology (Shanghai), Shanghai Ocean University, Shanghai 201306, China"},{"name":"Centre for Research on Environmental Ecology and Fish Nutrition of the Ministry of Agriculture, Shanghai 201306, China"},{"name":"National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai 201306, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0981-4513","authenticated-orcid":false,"given":"Yukun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Aquatic Animal Nutrition, Faculty of Fisheries, Kagoshima University, Kagoshima 890-0056, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6280-8118","authenticated-orcid":false,"given":"Weilong","family":"Wang","sequence":"additional","affiliation":[{"name":"China-ASEAN Belt and Road Joint Laboratory on Mariculture Technology (Shanghai), Shanghai Ocean University, Shanghai 201306, China"},{"name":"Centre for Research on Environmental Ecology and Fish Nutrition of the Ministry of Agriculture, Shanghai 201306, China"},{"name":"National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai 201306, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1146\/annurev-animal-030117-014838","article-title":"Meeting global feed protein demand: Challenge, opportunity, and strategy","volume":"7","author":"Kim","year":"2019","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"ref_2","first-page":"149","article-title":"Review on impacts of Litopenaeus vannamei on aquaculture","volume":"9","author":"Ranjula","year":"2021","journal-title":"WildLanka"},{"key":"ref_3","first-page":"30","article-title":"Water quality changes in the coastal area of intensive whiteleg shrimp brackish water pond aquaculture","volume":"61","author":"Mustafa","year":"2024","journal-title":"J. Water Land Dev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"124759","DOI":"10.1016\/j.chemosphere.2019.124759","article-title":"Effects of ammonia stress on the hemocytes of the Pacific white shrimp Litopenaeus vannamei","volume":"239","author":"Liu","year":"2020","journal-title":"Chemosphere"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.aquaculture.2011.05.015","article-title":"Antioxidant enzyme activities in Pacific white shrimp (Litopenaeus vannamei) in response to environmental hypoxia and reoxygenation","volume":"318","year":"2011","journal-title":"Aquaculture"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1590\/1678-4162-7942","article-title":"Hypoxia increases susceptibility of Pacific white shrimp to whitespot syndrome virus (WSSV)","volume":"68","author":"Lehmann","year":"2016","journal-title":"Arq. Bras. Med. Vet. Zootec."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1111\/raq.12429","article-title":"Effects of ammonia on shrimp physiology and immunity: A review","volume":"12","author":"Zhao","year":"2020","journal-title":"Rev. Aquac."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100389","DOI":"10.1016\/j.emcon.2024.100389","article-title":"Emergence of antibiotic resistance due to the excessive use of antibiotics in medicines and feed additives: A global scenario with emphasis on the Indian perspective","volume":"10","author":"Mithuna","year":"2024","journal-title":"Emerg. Contam."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e8","DOI":"10.1017\/gmb.2025.6","article-title":"Exploration of novel bioactive compounds from the microbiome of fish and shellfish as an alternative to replace antibiotic drugs in aquaculture farming","volume":"6","author":"Diwan","year":"2025","journal-title":"Gut Microbiome"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e31074","DOI":"10.1016\/j.heliyon.2024.e31074","article-title":"Exploring beneficial effects of phytobiotics in marine shrimp farming: A review","volume":"10","author":"Tahiluddin","year":"2024","journal-title":"Heliyon"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"46","DOI":"10.70102\/IJARES\/V2I2\/6","article-title":"A review on the application of phytogenics as feed additives for aquatic animals","volume":"2","author":"Kazempoor","year":"2022","journal-title":"Int. J. Aquat. Res. Environ. Stud."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3390\/pathogens4010137","article-title":"Phytogenic compounds as alternatives to in-feed antibiotics: Potentials and challenges in application","volume":"4","author":"Yang","year":"2015","journal-title":"Pathogens"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8825358","DOI":"10.1155\/2023\/8825358","article-title":"Emerging Therapeutic Potential of Cannabidiol (CBD) in Neurological Disorders: A Comprehensive Review","volume":"2023","author":"Singh","year":"2023","journal-title":"Behav. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1089\/can.2016.0034","article-title":"An update on safety and side effects of cannabidiol: A review of clinical data and relevant animal studies","volume":"2","author":"Iffland","year":"2017","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kicman, A., and Toczek, M. (2020). The Effects of Cannabidiol, a Non-Intoxicating Compound of Cannabis, on the Cardiovascular System in Health and Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186740"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/s41419-020-02892-1","article-title":"Cannabidiol (CBD): A killer for inflammatory rheumatoid arthritis synovial fibroblasts","volume":"11","author":"Lowin","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Atalay, S., Jarocka-Karpowicz, I., and Skrzydlewska, E. (2020). Antioxidative and Anti-Inflammatory Properties of Cannabidiol. Antioxidants, 9.","DOI":"10.3390\/antiox9010021"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Huang, C., Liang, H., Liang, X., Liu, Y., Wang, J., Jiang, H., Kou, X., Chen, J., and Huang, L. (2025). The protective role of cannabidiol in stress-induced liver injury: Modulating oxidative stress and mitochondrial damage. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1567210"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"NS20200080","DOI":"10.1042\/NS20200080","article-title":"Cannabidiol modulation of oxidative stress and signalling","volume":"5","author":"Pereira","year":"2021","journal-title":"Neuronal Signal."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.bcp.2008.06.022","article-title":"The profile of immune modulation by cannabidiol (CBD) involves deregulation of nuclear factor of activated T cells (NFAT)","volume":"76","author":"Kaplan","year":"2008","journal-title":"Biochem. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1089\/can.2018.0073","article-title":"Immune responses regulated by cannabidiol","volume":"5","author":"Nichols","year":"2020","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1111\/are.13512","article-title":"Effect of cannabis oil on growth performance, haematology and metabolism of Nile Tilapia Oreochromis niloticus","volume":"49","author":"Saoud","year":"2018","journal-title":"Aquac. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"106897","DOI":"10.1016\/j.applanim.2025.106897","article-title":"The effects of cannabidiol (CBD) in transport water on the behaviour of ornamental fishes","volume":"296","author":"Jones","year":"2025","journal-title":"Appl. Anim. Behav. Sci."},{"key":"ref_24","unstructured":"Juries, T.C. (2021). The Effects of Cannabidiol Oil Derived from Hemp on the Growth Performance and Wellbeing of Oreochromis Niloticus, Stellenbosch University."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17650","DOI":"10.1038\/s41598-022-21759-3","article-title":"Cannabidiol improves Nile tilapia cichlid fish welfare","volume":"12","author":"Bellot","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5375","DOI":"10.1111\/are.15407","article-title":"Effects of CBD (Cannabidiol) on the haematological parameters of Nile tilapia (Oreochromis niloticus, Linnaeus) under acute stress in vivo","volume":"52","author":"Mortuza","year":"2021","journal-title":"Aquac. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"739658","DOI":"10.1016\/j.aquaculture.2023.739658","article-title":"Effects of cannabidiol on growth performance, appetite, antioxidant capacity and liver inflammatory gene expression of juvenile large yellow croaker (Larmichthys crocea) fed diets with high soybean oil level","volume":"574","author":"Wang","year":"2023","journal-title":"Aquaculture"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e70015","DOI":"10.1111\/jfd.70015","article-title":"In Silico Assessment of Cannabidiol From Cannabis sativa as an Antiviral Agent Against Key Shrimp Pathogens in Aquaculture","volume":"49","author":"Gunasekaran","year":"2026","journal-title":"J. Fish. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Fantasma, F., D\u2019Urso, G., Martella, N., Capuano, A., Boccia, E., Samukha, V., De Felice, V., Saviano, G., Trombetta, F., and Lauro, G. (2025). Chemical Profiling of Polyphenolic Fraction of Cannabis sativa L. vr. Kompolti Industrial Inflorescences: Insights into Cannabidiol Neuroprotective Effects in a Cellular Model of Parkinson\u2019s Disease. Plants, 14.","DOI":"10.3390\/plants14101473"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12663","DOI":"10.3390\/molecules181012663","article-title":"Understanding the molecular aspects of tetrahydrocannabinol and cannabidiol as antioxidants","volume":"18","author":"Borges","year":"2013","journal-title":"Molecules"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ray, A.K., and Ring\u00f8, E. (2014). The gastrointestinal tract of fish. Aquaculture Nutrition: Gut Health, Probiotics and Prebiotics, John Wiley & Sons.","DOI":"10.1002\/9781118897263.ch1"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"B\u00f8gwald, J., and Dalmo, R.A. (2014). Gastrointestinal Pathogenesis in Aquatic Animals. Aquaculture Nutrition, John Wiley & Sons.","DOI":"10.1002\/9781118897263.ch3"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"De Filippis, D., Esposito, G., Cirillo, C., Cipriano, M., De Winter, B.Y., Scuderi, C., Sarnelli, G., Cuomo, R., Steardo, L., and De Man, J.G. (2011). Cannabidiol Reduces Intestinal Inflammation through the Control of Neuroimmune Axis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028159"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10550","DOI":"10.3389\/adar.2022.10550","article-title":"Role of gut microbiota in cannabinoid-mediated suppression of inflammation","volume":"2","author":"Varsha","year":"2022","journal-title":"Adv. Drug Alcohol. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/j.1365-2109.2009.02307.x","article-title":"Apparent digestibility of selected feed ingredients for white shrimp Litopenaeus vannamei, Boone","volume":"41","author":"Yang","year":"2009","journal-title":"Aquac. Res."},{"key":"ref_36","unstructured":"Arlington, V. (1995). Official Methods of Analysis of Official Analytical Chemists International, Association of Official Analytical Chemists (AOAC) International."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.cbpc.2004.07.010","article-title":"Changes in lipid class and fatty acid composition during development in white seabream (Diplodus sargus) eggs and larvae","volume":"139","author":"Cejas","year":"2004","journal-title":"Comp. Biochem. Physiol. Part B Biochem. Mol. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/S0022-2275(20)40190-7","article-title":"Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride\u2013methanol","volume":"5","author":"Morrison","year":"1964","journal-title":"J. Lipid Res."},{"key":"ref_39","unstructured":"(2000). Animal and Vegetable Fats and Oils\u2014Preparation of Methyl Esters of Fatty Acids (Standard No. ISO 5509)."},{"key":"ref_40","unstructured":"(2023). Quality Requirements for Enzyme Preparations\u2014Part 1: Protease Preparations (Standard No. GB\/T 23527.1-2023)."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8384917","DOI":"10.1155\/2022\/8384917","article-title":"An Evaluation of Replacing Soybean Meal with Proteolytic Soybean Meal in Low-Fish-Meal Diet on Growth Performance, Expression of Immune-Related Genes, and Resistance against Vibrio alginolyticus in White Shrimp (Litopenaeus vannamei)","volume":"2022","author":"Wang","year":"2022","journal-title":"Aquac. Nutr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.cbpc.2009.06.005","article-title":"Molecular characterization of hypoxia inducible factor-1 (HIF-1) from the white shrimp Litopenaeus vannamei and tissue-specific expression under hypoxia","volume":"150","author":"Forman","year":"2009","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Fang, H., He, X., Zeng, H., Liu, Y., Tian, L., and Niu, J. (2021). Replacement of Astaxanthin With Lutein in Diets of Juvenile Litopenaeus vannamei: Effects on Growth Performance, Antioxidant Capacity, and Immune Response. Front. Mar. Sci., 8.","DOI":"10.3389\/fmars.2021.803748"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Zhu, Q., Yang, Q., Shen, L., Xu, M., and Liu, M. (2025). The Impact of Cannabidiol (CBD) on Lipid Absorption and Lymphatic Transport in Rats. Nutrients, 17.","DOI":"10.3390\/nu17061034"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3694","DOI":"10.1038\/s41598-023-30872-w","article-title":"Cannabidiol improves muscular lipid profile by affecting the expression of fatty acid transporters and inhibiting de novo lipogenesis","volume":"13","author":"Bielawiec","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1016\/j.jhep.2015.01.001","article-title":"Two non-psychoactive cannabinoids reduce intracellular lipid levels and inhibit hepatosteatosis","volume":"62","author":"Silvestri","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"15952","DOI":"10.1038\/s41598-024-66599-5","article-title":"Cannabidiol effectively prevents oxidative stress and stabilizes hypoxia-inducible factor-1 alpha (HIF-1\u03b1) in an animal model of global hypoxia","volume":"14","author":"Kletkiewicz","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.molimm.2024.07.008","article-title":"The immunomodulatory effects of cannabidiol on Hsp70-activated NK cells and tumor target cells","volume":"174","author":"Wang","year":"2024","journal-title":"Mol. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1080\/17474124.2017.1343143","article-title":"The intestinal barrier: A fundamental role in health and disease","volume":"11","author":"Vancamelbeke","year":"2017","journal-title":"Expert. Rev. Gastroenterol. Hepatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.aquaculture.2018.09.026","article-title":"Metagenomic insights into the structure and function of intestinal microbiota of the farmed Pacific white shrimp (Litopenaeus vannamei)","volume":"499","author":"Gao","year":"2019","journal-title":"Aquaculture"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1111\/j.1365-2109.2003.00959.x","article-title":"Digestive enzyme activity and food ingesta in juvenile shrimp Litopenaeus vannamei (Boone, 1931) as a function of body weight","volume":"34","author":"Cahu","year":"2003","journal-title":"Aquac. Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Derome, N., Gauthier, J., Boutin, S., and Llewellyn, M. (2016). Bacterial opportunistic pathogens of fish. The Rasputin Effect: When Commensals and Symbionts Become Parasitic, Springer.","DOI":"10.1007\/978-3-319-28170-4_4"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1007\/s12275-024-00187-0","article-title":"Rhodobacteraceae are prevalent and ecologically crucial bacterial members in marine biofloc aquaculture","volume":"62","author":"Rajeev","year":"2024","journal-title":"J. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"388","DOI":"10.24272\/j.issn.2095-8137.2024.364","article-title":"Beneficial effects of probiotics on Litopenaeus vannamei growth and immune function via the recruitment of gut Rhodobacteraceae symbionts","volume":"46","author":"Sha","year":"2025","journal-title":"Zool. Res."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Mortuza, A., Fahim, N., Ahmed, M., and Mustafa, A. (2023). Effects of CBD (Cannabidiol) on the physiology of Nile tilapia (Oreochromisn niloticus) as a chronic stress mitigating agent In-vivo. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0290835"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"974","DOI":"10.2174\/1570159X17666190603171901","article-title":"Cannabidiol adverse effects and toxicity","volume":"17","author":"Huestis","year":"2019","journal-title":"Curr. Neuropharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.12688\/f1000research.19931.1","article-title":"Are adverse effects of cannabidiol (CBD) products caused by tetrahydrocannabinol (THC) contamination?","volume":"8","author":"Lachenmeier","year":"2019","journal-title":"F1000Research"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"S97","DOI":"10.1097\/j.pain.0000000000001963","article-title":"Adverse effects of heavy cannabis use: Even plants can harm the brain","volume":"162","author":"Sideli","year":"2021","journal-title":"Pain"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/4\/475\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T04:28:16Z","timestamp":1777004896000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/4\/475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,10]]},"references-count":59,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["antiox15040475"],"URL":"https:\/\/doi.org\/10.3390\/antiox15040475","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,10]]}}}