{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:47:14Z","timestamp":1790434034687,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,5,16]],"date-time":"2018-05-16T00:00:00Z","timestamp":1526428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Children and adults with frequent and severe episodes of epilepsy that do not respond to standard treatments (such as carbamazepine, phenytoin and valproate) have long been prescribed cannabidiol (CBD) as an anticonvulsant drug. However, the safety of its chronic use in relation to reproduction has not been fully examined. This study aimed to assess the effects of chronic CBD exposure on the male reproductive system. CBD was orally administered to 21\u2010day\u2010old male Swiss mice at doses of 15 and 30\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup> daily (CBD 15 and 30 groups, respectively), with a control group receiving sunflower oil, for 34 consecutive days. After a 35\u00a0day recovery period, the following parameters were evaluated: weight of reproductive organs, testosterone concentration, spermatogenesis, histomorphometry, daily sperm production and its morphology. The CBD 30 group had a 76% decrease in total circulating testosterone, but it remained within the physiological normal range (240\u20131100\u00a0ng\u00a0dl<jats:sup>\u22121<\/jats:sup>). CBD treatment induced a significant increase in the frequency of stages I\u2013IV and V\u2013VI of spermatogenesis, and a decrease in the frequency of stages VII\u2013VIII and XII. A significant decrease in the number of Sertoli cells was observed only in the CBD 30 group. In both CBD groups the number of spermatozoa in the epididymis tail was reduced by 38%, sperm had head abnormalities, and cytoplasmic droplets were observed in the medial region of flagellum. These results indicated that chronic CBD exposure was associated with changes in the male reproductive system, suggesting its reproductive toxicity.<\/jats:p>","DOI":"10.1002\/jat.3631","type":"journal-article","created":{"date-parts":[[2018,5,16]],"date-time":"2018-05-16T03:50:27Z","timestamp":1526442627000},"page":"1215-1223","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Chronic exposure to cannabidiol induces reproductive toxicity in male Swiss mice"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8263-3896","authenticated-orcid":false,"given":"Renata K.","family":"Carvalho","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Laboratory of Physiology and Pharmacology of Reproduction Universidade Federal de Goi\u00e1s  Goi\u00e2nia GO Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monaliza L.","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Laboratory of Physiology and Pharmacology of Reproduction Universidade Federal de Goi\u00e1s  Goi\u00e2nia GO Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maingredy R.","family":"Souza","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Laboratory of Physiology and Pharmacology of Reproduction Universidade Federal de Goi\u00e1s  Goi\u00e2nia GO Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0551-6842","authenticated-orcid":false,"given":"Thiago L.","family":"Rocha","sequence":"additional","affiliation":[{"name":"Institute of Tropical Pathology and Public Health Universidade Federal de Goi\u00e1s  Goi\u00e2nia GO Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4092-7778","authenticated-orcid":false,"given":"Francisco S.","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeir\u00e3o Preto Medical School Universidade de S\u00e3o Paulo  Ribeir\u00e3o Preto SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janete A.","family":"Anselmo\u2010Franci","sequence":"additional","affiliation":[{"name":"Department of Morphology, Stomatology and Physiology, Dental School of Ribeir\u00e3o Preto Universidade de S\u00e3o Paulo  Ribeir\u00e3o Preto SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0198-2910","authenticated-orcid":false,"given":"Renata","family":"Mazaro\u2010Costa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Laboratory of Physiology and Pharmacology of Reproduction Universidade Federal de Goi\u00e1s  Goi\u00e2nia GO Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0083-6729(08)60985-1"},{"key":"e_1_2_7_3_1","first-page":"20002","article-title":"Effects of \u03b1\u2010zearalanol on spermatogenesis and sex hormone levels of male mice","volume":"8","author":"Bo C.","year":"2015","journal-title":"International Journal of Clinical and Experimental Medicine"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1590\/0004-282X20150041"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145712001502"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.109.079210"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hup.1048"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1000930308"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)37153-9"},{"key":"e_1_2_7_10_1","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1007\/s00213-011-2415-0","article-title":"Plasma and brain pharmacokinetic profile of cannabidiol (CBD), cannabidivarine (CBDV), \u03949\u2010tetrahydrocannabivarin (THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessive\u2010compulsive behaviour","volume":"219","author":"Deiana S.","year":"2011","journal-title":"Psychopharmacology (Berlin)"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.867048"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(84)90111-4"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-461207-5.50025-0"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2013.02.002"},{"key":"e_1_2_7_15_1","first-page":"197","volume-title":"Male reproduction: a multidisciplinary overview","author":"Fran\u00e7a L. R.","year":"1998"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-1672"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2009.02.013"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812789106"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-013-1051-3"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/014850190898845"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-08-023759-6.50038-X"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-09597-4_1"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-013-1029-1"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3233\/CH-168021"},{"key":"e_1_2_7_25_1","series-title":"Part 2. Boar (Sus scrofa f. domestica)","volume-title":"Morphology of sperm: description, classification and assessment","author":"Leidl W.","year":"1999"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2012.15"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02536"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-3084(02)00144-5"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19020342"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.14.1.1"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deu116"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.98"},{"key":"e_1_2_7_33_1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0014-2999(02)02624-9","article-title":"(\u2212)\u2010Cannabidiol antagonizes cannabinoid receptor agonists and noradrenaline in the mouse vas deferens","volume":"456","author":"Pertwee R. G.","year":"2002","journal-title":"European Journal of Pharmacology"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2007.02.003"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0540103"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-0969"},{"key":"e_1_2_7_37_1","volume-title":"Comp\u00eandio de psiquiatria: ci\u00eancia do comportamento e psiquiatria cl\u00ednica","author":"Sadock B. J.","year":"2016"},{"key":"e_1_2_7_38_1","first-page":"1117","volume-title":"Fisiologia","author":"Spritzer P. M.","year":"2013"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00182038"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2011.188"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031287"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.5698\/1535-7597-14.5.250"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0106585"},{"key":"e_1_2_7_44_1","first-page":"341","article-title":"Developmental changes in signalling transduction factors in maturing sperm during epididymal transit","volume":"49","author":"Yeung C. H.","year":"2003","journal-title":"Cellular and Molecular Biology (Noisy\u2010le\u2010Grand, France)"}],"updated-by":[{"DOI":"10.1002\/jat.3731","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2018,9,11]],"date-time":"2018-09-11T00:00:00Z","timestamp":1536624000000}}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjat.3631","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.3631","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T12:49:54Z","timestamp":1760532594000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.3631"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,16]]},"references-count":43,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018,9]]}},"alternative-id":["10.1002\/jat.3631"],"URL":"https:\/\/doi.org\/10.1002\/jat.3631","archive":["Portico"],"relation":{"erratum":[{"id-type":"doi","id":"10.1002\/jat.3731","asserted-by":"object"}]},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,16]]},"assertion":[{"value":"2018-02-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}