{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T03:29:12Z","timestamp":1791602952331,"version":"4.3.4"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T00:00:00Z","timestamp":1622160000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>The endocannabinoid system is a neuromodulatory system responsible for partial regulation of cognitive and emotional processes in the human central nervous system such as behavior, mood disorders, and neurologic disorders such as epilepsy. The endocannabinoid system is also prevalent throughout the peripheral nervous system and human body and its receptors and signaling pathways are present and active in areas including the male and female reproductive tracts and organ systems such as the urologic and gastrointestinal system.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Summary:<\/jats:title>\n            <jats:p>The purpose of this article is to provide the reader with a brief background on the endocannabinoid system and to discuss the implications of the endocannabinoid system in urology as it applies to the male reproductive system, risk of urologic malignancy, and impact on the lower urinary tract, voiding, and urologic pain. It also summaries and discusses the epidemiology and research on cannabis and cannabidiol products.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Key message:<\/jats:title>\n            <jats:p>The endocannabinoid system affects the urologic and reproductive systems. Cannabis products and inhibitors targeting endocannabinoid pathways are being studied for their potential use as treatments for lower urinary tract symptoms and other urologic symptoms. Cannabis use adversely affects spermatogenesis and semen parameters and may be a risk factor for testicular germ cell tumors, however, it may be useful as a potential treatment for urologic symptoms. Cannabidiol products are popular in the consumer marketplace but there is still a paucity of scientific data on their potential medicinal use.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/cu9.0000000000000023","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T21:06:29Z","timestamp":1623963989000},"page":"95-100","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":24,"title":["The endocannabinoid system, cannabis, and cannabidiol: Implications in urology and men's health"],"prefix":"10.1097","volume":"15","author":[{"given":"Jillian L.","family":"Capodice","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Kaplan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,5,28]]},"reference":[{"issue":"(9)","key":"R1-20250821","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.tips.2009.06.006","article-title":"The therapeutic potential of the endocannabinoid system for the development of a novel class of antidepressants","volume":"30","author":"Hill","year":"2009","journal-title":"Trends Pharmacol Sci"},{"key":"R2-20250821","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/S0090-6980(02)00060-6","article-title":"The cannabinoid receptors","volume":"68\u201369","author":"Howlett","year":"2002","journal-title":"Prostaglandins Other Lipid Mediat"},{"issue":"(6284)","key":"R3-20250821","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/346561a0","article-title":"Structure of a cannabinoid receptor and functional expression of the cloned cDNA","volume":"346","author":"Matsuda","year":"1990","journal-title":"Nature"},{"issue":"(1\u20132)","key":"R4-20250821","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0090-6980(00)00051-4","article-title":"Biochemistry and pharmacology of the endocannabinoids arachidonylethanolamide and 2-arachidonylglycerol","volume":"61","author":"Hillard","year":"2000","journal-title":"Prostaglandins Other Lipid Mediat"},{"key":"R5-20250821","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1021\/cr0782067","article-title":"Enzymatic pathways that regulate endocannabinoid signaling in the nervous system","volume":"108","author":"Ahn","year":"2008","journal-title":"Chem Rev"},{"issue":"(8)","key":"R6-20250821","doi-asserted-by":"crossref","first-page":"e0133292","DOI":"10.1371\/journal.pone.0133292","article-title":"The genetic structure of marijuana and hemp","volume":"10","author":"Sawler","year":"2015","journal-title":"PLoS One"},{"key":"R8-20250821","first-page":"35","article-title":"History of therapeutic cannabis","author":"Aldrich","year":"1997","journal-title":"Cannabis in Medical Practice: A Legal, Historical and Pharmacological Overview of the Therapeutic Use of Marijuana"},{"key":"R9-20250821","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.jep.2018.09.004","article-title":"Cannabis sativa: a comprehensive ethnopharmacological review of a medicinal plant with a long history","volume":"227","author":"Bonini","year":"2018","journal-title":"J Ethnopharmacol"},{"key":"R10-20250821","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fpls.2016.00019","article-title":"Cannabis sativa: the plant of the thousand and one molecules","volume":"7","author":"Andre","year":"2016","journal-title":"Front Plant Sci"},{"issue":"(9)","key":"R11-20250821","doi-asserted-by":"crossref","first-page":"e13370","DOI":"10.1111\/nmo.13370","article-title":"Cannabinoids and gastrointestinal motility: pharmacology, clinical effects, and potential therapeutics in humans","volume":"30","author":"Camilleri","year":"2018","journal-title":"Neurogastroenterol Motil"},{"issue":"(4)","key":"R12-20250821","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.addbeh.2005.05.052","article-title":"Decreased depression in marijuana users","volume":"31","author":"Denson","year":"2006","journal-title":"Addict Behav"},{"issue":"(2)","key":"R13-20250821","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1523\/JNEUROSCI.11-02-00563.1991","article-title":"Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study","volume":"11","author":"Herkenham","year":"1991","journal-title":"J Neurosci"},{"issue":"(5\u20136)","key":"R14-20250821","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1097\/00008877-200509000-00006","article-title":"Is there a role for the endocannabinoid system in the etiology and treatment of melancholic depression?","volume":"16","author":"Hill","year":"2005","journal-title":"Behav Pharmacol"},{"issue":"(1)","key":"R15-20250821","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.psyneuen.2007.09.008","article-title":"Antidepressant-like behavioral effects of impaired cannabinoid receptor type 1 signaling coincide with exaggerated corticosterone secretion in mice","volume":"33","author":"Steiner","year":"2008","journal-title":"Psychoneuroendocrinology"},{"issue":"(7)","key":"R17-20250821","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1016\/j.bmc.2015.01.059","article-title":"Cannabidiol (CBD) and its analogs: a review of their effects on inflammation","volume":"23","author":"Burstein","year":"2015","journal-title":"Bioorg Med Chem"},{"key":"R18-20250821","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3389\/fpsyt.2019.00063","article-title":"The endocannabinoid system and cannabidiol's promise for the treatment of substance use disorder","volume":"10","author":"Chye","year":"2019","journal-title":"Front Psychiatry"},{"key":"R19-20250821","doi-asserted-by":"crossref","first-page":"4790","DOI":"10.1111\/bph.13250","article-title":"Cannabidiol is a negative allosteric modulator of the cannabinoid CB 1 receptor","volume":"172","author":"Laprairie","year":"2015","journal-title":"Br J Pharmacol"},{"issue":"(1)","key":"R20-20250821","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13048-018-0478-9","article-title":"The role of the endocannabinoid system in female reproductive tissues","volume":"12","author":"Walker","year":"2019","journal-title":"J Ovarian Res"},{"key":"R21-20250821","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.pain.2010.08.037","article-title":"Endocannabinoid involvement in endometriosis","volume":"151","author":"Dmitrieva","year":"2010","journal-title":"Pain"},{"issue":"(5)","key":"R22-20250821","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1097\/MNH.0000000000000249","article-title":"Cannabinoid receptors in the kidney","volume":"25","author":"Hryciw","year":"2016","journal-title":"Curr Opin Nephrol Hypertens"},{"issue":"(2)","key":"R23-20250821","doi-asserted-by":"crossref","first-page":"e12875","DOI":"10.1111\/and.12875","article-title":"Expression and distribution of key proteins of the endocannabinoid system in the human seminal vesicles","volume":"50","author":"\u00dcckert","year":"2018","journal-title":"Andrologia"},{"issue":"(1)","key":"R24-20250821","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1095\/biolreprod.106.051730","article-title":"Endocannabinoid system in frog and rodent testis: type-1 cannabinoid receptor and fatty acid amide hydrolase activity in male germ cells","volume":"75","author":"Cobellis","year":"2006","journal-title":"Biol Reprod"},{"issue":"(2)","key":"R25-20250821","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.eururo.2008.12.024","article-title":"Localization and function of cannabinoid receptors in the corpus cavernosum: basis for modulation of nitric oxide synthase nerve activity","volume":"57","author":"Gratzke","year":"2010","journal-title":"Eur Urol"},{"issue":"(10)","key":"R26-20250821","doi-asserted-by":"crossref","first-page":"4692","DOI":"10.1210\/en.2009-0057","article-title":"Characterization of the endocannabinoid system in human spermatozoa and involvement of transient receptor potential vanilloid 1 receptor in their fertilizing ability","volume":"150","author":"Francavilla","year":"2009","journal-title":"Endocrinology"},{"issue":"(11)","key":"R27-20250821","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0165-6147(00)01805-8","article-title":"Modulation of transmitter release via presynaptic cannabinoid receptors","volume":"22","author":"Schlicker","year":"2001","journal-title":"Trends Pharmacol Sci"},{"issue":"(2)","key":"R28-20250821","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1210\/jc.2004-1287","article-title":"Human sperm express cannabinoid receptor Cb1, the activation of which inhibits motility, acrosome reaction, and mitochondrial function","volume":"90","author":"Rossato","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"issue":"(6)","key":"R29-20250821","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1111\/j.1743-6109.2012.02708.x","article-title":"Circulating endocannabinoid concentrations and sexual arousal in women","volume":"9","author":"Klein","year":"2012","journal-title":"J Sex Med"},{"issue":"(11)","key":"R30-20250821","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1016\/j.jsxm.2017.09.016","article-title":"Masturbation to orgasm stimulates the release of the endocannabinoid 2-arachidonoylglycerol in humans","volume":"14","author":"Fuss","year":"2017","journal-title":"J Sex Med"},{"issue":"(10)","key":"R33-20250821","doi-asserted-by":"crossref","first-page":"e76635","DOI":"10.1371\/journal.pone.0076635","article-title":"The global epidemiology and contribution of cannabis use and dependence to the global burden of disease: results from the GBD 2010 study","volume":"8","author":"Degenhardt","year":"2013","journal-title":"PLoS One"},{"issue":"(6)","key":"R34-20250821","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1093\/aje\/kwv135","article-title":"Association between use of marijuana and male reproductive hormones and semen quality: a study among 1,215 healthy young men","volume":"182","author":"Gundersen","year":"2015","journal-title":"Am J Epidemiol"},{"issue":"(4)","key":"R35-20250821","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1097\/JU.0000000000000248","article-title":"Cannabis and male fertility: a systematic review","volume":"202","author":"Payne","year":"2019","journal-title":"J Urol"},{"issue":"(8)","key":"R36-20250821","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1093\/humrep\/deu116","article-title":"Modifiable and non-modifiable risk factors for poor sperm morphology","volume":"29","author":"Pacey","year":"2014","journal-title":"Hum Reprod"},{"issue":"(3)","key":"R37-20250821","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/bdrb.20295","article-title":"Effects of chronic bhang [cannabis] administration on the reproductive system of male mice","volume":"92","author":"Banerjee","year":"2011","journal-title":"Birth Defects Res B Dev Reprod Toxicol"},{"issue":"(2)","key":"R38-20250821","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/andr.12585","article-title":"The relationship between cannabis and male infertility, sexual health, and neoplasm: a systematic review","volume":"7","author":"Rajanahally","year":"2019","journal-title":"Andrology"},{"issue":"(6)","key":"R39-20250821","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1002\/cncr.24159","article-title":"Association of marijuana use and the incidence of testicular germ cell tumors","volume":"115","author":"Daling","year":"2009","journal-title":"Cancer"},{"key":"R40-20250821","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1186\/s12885-015-1905-6","article-title":"Cannabis exposure and risk of testicular cancer: a systematic review and meta-analysis","volume":"15","author":"Gurney","year":"2015","journal-title":"BMC Cancer"},{"issue":"(1)","key":"R41-20250821","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.urology.2005.07.005","article-title":"Association between marijuana use and transitional cell carcinoma","volume":"67","author":"Chacko","year":"2006","journal-title":"Urology"},{"issue":"(2)","key":"R42-20250821","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.urology.2014.08.060","article-title":"Association between cannabis use and the risk of bladder cancer: results from the California Men's Health Study","volume":"85","author":"Thomas","year":"2015","journal-title":"Urology"},{"issue":"(5)","key":"R43-20250821","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s00192-012-1954-1","article-title":"Distribution and function of the endocannabinoid system in the rat and human bladder","volume":"24","author":"Bakali","year":"2013","journal-title":"Int Urogynecol J"},{"issue":"(23)","key":"R44-20250821","doi-asserted-by":"crossref","first-page":"13396","DOI":"10.1073\/pnas.231243698","article-title":"Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells","volume":"98","author":"Birder","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"(1\u20132)","key":"R45-20250821","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0304-3959(01)00419-5","article-title":"Attenuation of nerve growth factor-induced visceral hyperalgesia via cannabinoid CB(1) and CB(2)-like receptors","volume":"97","author":"Farquhar-Smith","year":"2002","journal-title":"Pain"},{"issue":"(4)","key":"R46-20250821","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1191\/1352458504ms1063oa","article-title":"An open-label pilot study of cannabis-based extracts for bladder dysfunction in advanced multiple sclerosis","volume":"10","author":"Brady","year":"2004","journal-title":"Mult Scler"},{"issue":"(6)","key":"R47-20250821","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1007\/s00192-006-0086-x","article-title":"The effect of cannabis on urge incontinence in patients with multiple sclerosis: a multicentre, randomised placebo-controlled trial (CAMS-LUTS)","volume":"17","author":"Freeman","year":"2006","journal-title":"Int Urogynecol J Pelvic Floor Dysfunct"},{"issue":"(suppl 3)","key":"R48-20250821","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/bcpt.12577","article-title":"Potential future pharmacological treatment of bladder dysfunction","volume":"119","author":"Andersson","year":"2016","journal-title":"Basic Clin Pharmacol Toxicol"},{"issue":"(2)","key":"R49-20250821","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1124\/pr.112.006387","article-title":"Chemical probes of endocannabinoid metabolism","volume":"65","author":"Blankman","year":"2013","journal-title":"Pharmacol Rev"},{"key":"R50-20250821","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.urology.2017.02.029","article-title":"Fatty acid amide hydrolase inhibitor treatment in men with chronic prostatitis\/chronic pelvic pain syndrome: an adaptive double-blind, randomized controlled trial","volume":"103","author":"Wagenlehner","year":"2017","journal-title":"Urology"},{"key":"R51-20250821","doi-asserted-by":"crossref","first-page":"223.e9","DOI":"10.1016\/j.urology.2017.08.011","article-title":"Impact of regular cannabis use on biomarkers of lower urinary tract function","volume":"109","author":"Nedumaran","year":"2017","journal-title":"Urology"},{"issue":"(9)","key":"R52-20250821","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1016\/j.mayocp.2019.01.003","article-title":"Clinicians\u2019 guide to cannabidiol and hemp oils","volume":"94","author":"VanDolah","year":"2019","journal-title":"Mayo Clin Proc"},{"issue":"(11)","key":"R53-20250821","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1007\/s40263-018-0578-5","article-title":"A phase I, randomized, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect trial of the safety, tolerability and pharmacokinetics of highly purified cannabidiol in healthy subjects","volume":"32","author":"Taylor","year":"2018","journal-title":"CNS Drugs"},{"issue":"(11)","key":"R54-20250821","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1176\/appi.ajp.2019.18101191","article-title":"Cannabidiol for the reduction of cue-induced craving and anxiety in drug-abstinent individuals with heroin use disorder: a double-blind randomized placebo-controlled trial","volume":"176","author":"Hurd","year":"2019","journal-title":"Am J Psychiatry"}],"container-title":["Current Urology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/CU9.0000000000000023","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T17:00:19Z","timestamp":1755795619000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/CU9.0000000000000023"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,28]]},"references-count":50,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.1097\/cu9.0000000000000023","relation":{},"ISSN":["1661-7649","1661-7657"],"issn-type":[{"value":"1661-7649","type":"print"},{"value":"1661-7657","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,28]]},"assertion":[{"value":"2020-02-27","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-16","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}