Marijuana, Alcohol, and ED: Correlations with LUTS/BPH

Abstract

Purpose of Review

Benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) is a disease complex with enormous societal burden and yet the pathogenesis of LUTS/BPH is poorly understood. We set out to review the literature on the relationship between depression, marijuana usage, and erectile dysfunction (ED) to LUTS/BPH.

Recent Findings

LUTS/BPH has independent associations with depression as well as with ED. In each case, the causality and mechanistic relationship is unknown. The impact of marijuana, as it increasingly pervades the general population, on the disease complex of LUTS/BPH is not well studied but recent results support short-term benefit and long-term caution.

Summary

Depression, a form of central nervous dysfunction, and ED, which is likely mediated via endothelial dysfunction, are independently associated with LUTS/BPH. The presence of cannabinoid receptors in urologic organs, coupled with recent population studies, supports a modulatory effect of marijuana on voiding although an enormous knowledge gap remains.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    Murray CJ, Vos T, Lozano R, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2197–223.

    PubMed  Google Scholar 

  2. 2.

    • Gacci M, Corona G, Vignozzi L, et al. Metabolic syndrome and benign prostatic enlargement: a systematic review and meta-analysis. BJU Int. 2015;115(1):24–31. Excellent review of this topic.

    PubMed  PubMed Central  Google Scholar 

  3. 3.

    Platz EA, Kawachi I, Rimm EB, Colditz GA, Stampfer MJ, Willett WC, et al. Physical activity and benign prostatic hyperplasia. Arch Intern Med. 1998;158(21):2349–56.

    CAS  PubMed  Google Scholar 

  4. 4.

    Parsons JK, Kashefi C. Physical activity, benign prostatic hyperplasia, and lower urinary tract symptoms. Eur Urol. 2008;53(6):1228–35.

    PubMed  Google Scholar 

  5. 5.

    McVary KT, Rademaker A, Lloyd GL, Gann P. Autonomic nervous system overactivity in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol. 2005;174(4 Pt 1):1327–433.

    PubMed  Google Scholar 

  6. 6.

    Castro P, Giri D, Lamb D, Ittmann M. Cellular senescence in the pathogenesis of benign prostatic hyperplasia. Prostate. 2003;55(1):30–8.

    CAS  PubMed  Google Scholar 

  7. 7.

    Vital P, Castro P, Tsang S, Ittmann M. The senescence-associated secretory phenotype promotes benign prostatic hyperplasia. Am J Pathol. 2014;184(3):721–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Brookes ST, Link CL, Donovan JL, McKinlay JB. Relationship between lower urinary tract symptoms and erectile dysfunction: results from the Boston Area Community Health Survey. J Urol. 2008;179(1):250–5. discussion 255.

    PubMed  Google Scholar 

  9. 9.

    Johnson TV, Abbasi A, Ehrlich SS, Kleris RS, Chirumamilla SL, Schoenberg ED, et al. Major depression drives severity of American Urological Association Symptom Index. Urology. 2010;76(6):1317–20.

    PubMed  Google Scholar 

  10. 10.

    Johnson TV, Goodman M, Master VA. The efficacy of written screening tools in an inner city hospital: literacy based limitations on patient access to appropriate care. J Urol. 2007;178(2):623–9. discussion 629.

    PubMed  Google Scholar 

  11. 11.

    Madersbacher S, Alivizatos G, Nordling J, Sanz CR, Emberton M, de la Rosette JJ. EAU 2004 guidelines on assessment, therapy and follow-up of men with lower urinary tract symptoms suggestive of benign prostatic obstruction (BPH guidelines). Eur Urol. 2004;46(5):547–54.

    PubMed  Google Scholar 

  12. 12.

    Hagberg KW, Divan HA, Nickel JC, Jick SS. Risk of incident antidepressant-treated depression associated with use of 5alpha-reductase inhibitors compared with use of alpha-blockers in men with benign prostatic hyperplasia: a population-based study using the Clinical Practice Research Datalink. Pharmacotherapy. 2017;37(5):517–27.

    CAS  PubMed  Google Scholar 

  13. 13.

    Lloyd GL, Carmichael H. Marijuana, alcohol, ED, and depression: epidemiologic correlations with BPH/LUTS. AUA. 2019;2019.

  14. 14.

    Nielsen S, Germanos R, Weier M, Pollard J, Degenhardt L, Hall W, et al. The use of cannabis and cannabinoids in treating symptoms of multiple sclerosis: a systematic review of reviews. Curr Neurol Neurosci Rep. 2018;18(2):8.

    PubMed  Google Scholar 

  15. 15.

    Freeman RM, Adekanmi O, Waterfield MR, Waterfield AE, Wright D, Zajicek J. The effect of cannabis on urge incontinence in patients with multiple sclerosis: a multicentre, randomised placebo-controlled trial (CAMS-LUTS). Int Urogynecol J Pelvic Floor Dysfunct. 2006;17(6):636–41.

    CAS  PubMed  Google Scholar 

  16. 16.

    Brady CM, DasGupta R, Dalton C, Wiseman OJ, Berkley KJ, Fowler CJ. An open-label pilot study of cannabis-based extracts for bladder dysfunction in advanced multiple sclerosis. Mult Scler. 2004;10(4):425–33.

    CAS  PubMed  Google Scholar 

  17. 17.

    Consroe P, Musty R, Rein J, Tillery W, Pertwee R. The perceived effects of smoked cannabis on patients with multiple sclerosis. Eur Neurol. 1997;38(1):44–8.

    CAS  PubMed  Google Scholar 

  18. 18.

    Tackett B WD. The history of marijuana: learn about the origin of marijuana. In: Thomas S, ed. Recovery.org: American Addiction Centers; 2019. https://www.recovery.org/marijuana/history/. Apr 2020

  19. 19.

    Black N, Stockings E, Campbell G, Tran LT, Zagic D, Hall WD, et al. Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis. Lancet Psychiatry. 2019;6(12):995–1010.

    PubMed  PubMed Central  Google Scholar 

  20. 20.

    WB OS. On the preparations of the Indian Hemp, or Gunjah: Cannabis indica their effects on the animal system in health, and their utility in the treatment of tetanus and other convulsive diseases. Prov Med J Retrosp Med Sci. 1843;5:363–9.

    Google Scholar 

  21. 21.

    Zou S, Kumar U. Cannabinoid receptors and the endocannabinoid system: signaling and function in the central nervous system. Int J Mol Sci. 2018;19(3).

  22. 22.

    •• Gratzke C, Streng T, Stief CG, et al. Effects of cannabinor, a novel selective cannabinoid 2 receptor agonist, on bladder function in normal rats. Eur Urol. 2010;57(6):1093–100. A key animal model result showing impact on voiding.

    CAS  PubMed  Google Scholar 

  23. 23.

    Dmitrieva NBK. Contrasting effects of WIN 55212–2 on motility of the rat bladder and uterus. J Neurosci. 2002;22(16):7147–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Hiragata S, Ogawa T, Hayashi Y, Tyagi P, Seki S, Nishizawa O, et al. Effects of IP-751, ajulemic acid, on bladder overactivity induced by bladder irritation in rats. Urology. 2007;70(1):202–8.

    PubMed  Google Scholar 

  25. 25.

    Wang ZY, Wang P, Bjorling DE. Treatment with a cannabinoid receptor 2 agonist decreases severity of established cystitis. J Urol. 2014;191(4):1153–8.

    CAS  PubMed  Google Scholar 

  26. 26.

    Bjorling DE, Wang ZY. Potential of endocannabinoids to control bladder pain. Front Syst Neurosci. 2018;12:17.

    PubMed  PubMed Central  Google Scholar 

  27. 27.

    Nedumaran B, Rudra P, Gaydos J, et al. Impact of regular cannabis use on biomarkers of lower urinary tract function. Urology. 2017;109:223 e229–16.

    Google Scholar 

  28. 28.

    • Fantus RJ, Riedinger CB, Chang C, Helfand BT. The association between tetrahydrocannabinol and lower urinary tract symptoms utilizing the National Health and Nutrition Examination Survey. Urology. 2019;123:120–5. Report of associations in humans, key initial data on this topic.

    PubMed  Google Scholar 

  29. 29.

    Lloyd GL, Carmichael, H. Marijuana, alcohol, ED and depression: epidemiologic correlations with BPH/LUTS. AUA 2019; 2019; Chicago.

  30. 30.

    Mauro PM SD, Hasin D, Sarvet AL, Rahim-Juwel R, Brown Q, Carliner H, Wall M, Martins SS. Age differences in adult past-year marijuana use and risk perceptions in the U.S., 2002–2013. Drug Alcohol Dependence. 2017;171:e134.

  31. 31.

    Shahani R, Streutker C, Dickson B, Stewart RJ. Ketamine-associated ulcerative cystitis: a new clinical entity. Urology. 2007;69(5):810–2.

    PubMed  Google Scholar 

  32. 32.

    Koppel BS, Brust JC, Fife T, et al. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the guideline development Subcommittee of the American Academy of Neurology. Neurology. 2014;82(17):1556–63.

    PubMed  PubMed Central  Google Scholar 

  33. 33.

    Cuijpers P, Smit F. Excess mortality in depression: a meta-analysis of community studies. J Affect Disord. 2002;72(3):227–36.

    PubMed  Google Scholar 

  34. 34.

    Association AP. Diagnostic and statistical manual of mental disorders: diagnostic and statistical manual of mental disorders. Vol 5. Fifth ed. Arlington: American Psychiatric Association; 2013.

    Google Scholar 

  35. 35.

    Lee YI, Kim JW, Bae SR, Paick SH, Kim KW, Kim HG, et al. Effect of urgency symptoms on the risk of depression in community-dwelling elderly men. Korean J Urol. 2013;54(11):762–6.

    PubMed  PubMed Central  Google Scholar 

  36. 36.

    Martin S, Vincent A, Taylor AW, Atlantis E, Jenkins A, Januszewski A, et al. Lower urinary tract symptoms, depression, anxiety and systemic inflammatory factors in men: a population-based cohort study. PLoS One. 2015;10(10):e0137903.

    PubMed  PubMed Central  Google Scholar 

  37. 37.

    Koh JS, Ko HJ, Wang SM, Cho KJ, Kim JC, Lee SJ, et al. The relationship between depression, anxiety, somatization, personality and symptoms of lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Psychiatry Investig. 2015;12(2):268–73.

    PubMed  Google Scholar 

  38. 38.

    Breyer BN, Shindel AW, Erickson BA, Blaschko SD, Steers WD, Rosen RC. The association of depression, anxiety and nocturia: a systematic review. J Urol. 2013;190(3):953–7.

    PubMed  PubMed Central  Google Scholar 

  39. 39.

    Ou MJ, Huang CC, Wang YC, Chen YL, Ho CH, Wu MP, et al. Depression is a major risk factor for the development of dementia in people with lower urinary tract symptoms: a nationwide population-based study. PLoS One. 2019;14(6):e0217984.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Kim TH, Han DH, Ryu DS, Lee KS. The impact of lower urinary tract symptoms on quality of life, work productivity, depressive symptoms, and sexuality in Korean men aged 40 years and older: a population-based survey. Int Neurourol J. 2015;19(2):120–9.

    PubMed  PubMed Central  Google Scholar 

  41. 41.

    Jeong SM, Suh B, Jang SH, Jin HS, Kim N, Kwon H, et al. Depression and its severity are strongly associated with both storage and voiding lower urinary tract symptoms independently of prostate volume. J Korean Med Sci. 2015;30(11):1646–51.

    PubMed  PubMed Central  Google Scholar 

  42. 42.

    Breyer BN, Kenfield SA, Blaschko SD, Erickson BA. The association of lower urinary tract symptoms, depression and suicidal ideation: data from the 2005-2006 and 2007-2008 National Health and Nutrition Examination Survey. J Urol. 2014;191(5):1333–9.

    PubMed  Google Scholar 

  43. 43.

    Huang CY, Chiu KM, Chung SD, Keller JJ, Huang CC, Lin HC. Increased risk of depressive disorder following the diagnosis of benign prostatic enlargement: one-year follow-up study. J Affect Disord. 2011;135(1–3):395–9.

    PubMed  Google Scholar 

  44. 44.

    Dunphy C, Laor L, Te A, Kaplan S, Chughtai B. Relationship between depression and lower urinary tract symptoms secondary to benign prostatic hyperplasia. Rev Urol. 2015;17(2):51–7.

    PubMed  PubMed Central  Google Scholar 

  45. 45.

    Chung RY, Leung JC, Chan DC, Woo J, Wong CK, Wong SY. Lower urinary tract symptoms (LUTS) as a risk factor for depressive symptoms in elderly men: results from a large prospective study in southern Chinese men. PLoS One. 2013;8(9):e76017.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Agrawal A, Nelson EC, Bucholz KK, Tillman R, Grucza RA, Statham DJ, et al. Major depressive disorder, suicidal thoughts and behaviours, and cannabis involvement in discordant twins: a retrospective cohort study. Lancet Psychiatry. 2017;4(9):706–14.

    PubMed  PubMed Central  Google Scholar 

  47. 47.

    Volkow ND, Compton WM, Weiss SR. Adverse health effects of marijuana use. N Engl J Med. 2014;371(9):879.

    PubMed  Google Scholar 

  48. 48.

    Silins EHL, Patton GC, et al. Young adult sequelae of adolescent cannabis use: an integrative analysis. Lancet Psychiatry. 2014;1(4):286–93.

    PubMed  Google Scholar 

  49. 49.

    Gobbi G, Atkin T, Zytynski T, Wang S, Askari S, Boruff J, et al. Association of cannabis use in adolescence and risk of depression, anxiety, and suicidality in young adulthood: a systematic review and meta-analysis. JAMA Psychiatry. 2019;76(4):426–34.

    PubMed  PubMed Central  Google Scholar 

  50. 50.

    Gilman JM, Kuster JK, Lee S, Lee MJ, Kim BW, Makris N, et al. Cannabis use is quantitatively associated with nucleus accumbens and amygdala abnormalities in young adult recreational users. J Neurosci. 2014;34(16):5529–38.

    PubMed  PubMed Central  Google Scholar 

  51. 51.

    Bambico FR, Nguyen NT, Katz N, Gobbi G. Chronic exposure to cannabinoids during adolescence but not during adulthood impairs emotional behaviour and monoaminergic neurotransmission. Neurobiol Dis. 2010;37(3):641–55.

    CAS  PubMed  Google Scholar 

  52. 52.

    Hill MN, Campolongo P, Yehuda R, Patel S. Integrating endocannabinoid signaling and cannabinoids into the biology and treatment of posttraumatic stress disorder. Neuropsychopharmacology. 2018;43(1):80–102.

    PubMed  Google Scholar 

  53. 53.

    Marchant J. Placebos: honest fakery. Nature. 2016;535(7611):S14–5.

    PubMed  Google Scholar 

  54. 54.

    Dutkiewicz S, Skawinski D, Duda W, Duda M. Assessing the influence of benign prostatic hyperplasia (BPH) on erectile dysfunction (ED) among patients in Poland. Cent European J Urol. 2012;65(3):135–8.

    PubMed  PubMed Central  Google Scholar 

  55. 55.

    Yafi FA, Jenkins L, Albersen M, Corona G, Isidori AM, Goldfarb S, et al. Erectile dysfunction. Nat Rev Dis Primers. 2016;2:16003.

    PubMed  PubMed Central  Google Scholar 

  56. 56.

    Impotence: NIH Consensus Development Panel on Impotence. JAMA. 1993;270(1):83–90.

  57. 57.

    Ende J. Organic impotence. In: rd, Walker HK, hall WD, Hurst JW, eds. Clinical Methods: The History, Physical, and Laboratory Examinations. Boston 1990.

  58. 58.

    Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994;151(1):54–61.

    CAS  PubMed  Google Scholar 

  59. 59.

    Glina S, Glina FP. Pathogenic mechanisms linking benign prostatic hyperplasia, lower urinary tract symptoms and erectile dysfunction. Ther Adv Urol. 2013;5(4):211–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Li MK, Garcia L, Patron N, Moh LC, Sundram M, Leungwattanakij S, et al. An Asian multinational prospective observational registry of patients with benign prostatic hyperplasia, with a focus on comorbidities, lower urinary tract symptoms and sexual function. BJU Int. 2008;101(2):197–202.

    PubMed  Google Scholar 

  61. 61.

    Braun MH, Sommer F, Haupt G, Mathers MJ, Reifenrath B, Engelmann UH. Lower urinary tract symptoms and erectile dysfunction: co-morbidity or typical “aging male” symptoms? Results of the “Cologne Male Survey”. Eur Urol. 2003;44(5):588–94.

    CAS  PubMed  Google Scholar 

  62. 62.

    Rosen RC, Giuliano F, Carson CC. Sexual dysfunction and lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Eur Urol. 2005;47(6):824–37.

    PubMed  Google Scholar 

  63. 63.

    Rosen RC, Wei JT, Althof SE, Seftel AD, Miner M, Perelman MA, et al. Association of sexual dysfunction with lower urinary tract symptoms of BPH and BPH medical therapies: results from the BPH Registry. Urology. 2009;73(3):562–6.

    PubMed  Google Scholar 

  64. 64.

    Shridharani AN, Brant WO. The treatment of erectile dysfunction in patients with neurogenic disease. Transl Androl Urol. 2016;5(1):88–101.

    PubMed  PubMed Central  Google Scholar 

  65. 65.

    Kaya C, Uslu Z, Karaman I. Is endothelial function impaired in erectile dysfunction patients? Int J Impot Res. 2006;18(1):55–60.

    CAS  PubMed  Google Scholar 

  66. 66.

    Billups KL. Erectile dysfunction as an early sign of cardiovascular disease. Int J Impot Res. 2005;17(Suppl 1):S19–24.

    PubMed  Google Scholar 

  67. 67.

    Hughes FM Jr, Hill HM, Wood CM, et al. The NLRP3 inflammasome mediates inflammation produced by bladder outlet obstruction. J Urol. 2016;195(5):1598–605.

    CAS  PubMed  Google Scholar 

  68. 68.

    Gacci M, Andersson KE, Chapple C, Maggi M, Mirone V, Oelke M, et al. Latest evidence on the use of phosphodiesterase type 5 inhibitors for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. Eur Urol. 2016;70(1):124–33.

    CAS  PubMed  Google Scholar 

  69. 69.

    Carliner H, Brown QL, Sarvet AL, Hasin DS. Cannabis use, attitudes, and legal status in the U.S.: a review. Prev Med. 2017;104:13–23.

    PubMed  PubMed Central  Google Scholar 

  70. 70.

    • Shamloul R, Bella AJ. Impact of cannabis use on male sexual health. J Sex Med. 2011;8(4):971–5. Important data for public health and clinical care.

    PubMed  Google Scholar 

  71. 71.

    Argiolas A, Melis MR. Central control of penile erection: role of the paraventricular nucleus of the hypothalamus. Prog Neurobiol. 2005;76(1):1–21.

    CAS  PubMed  Google Scholar 

  72. 72.

    Gratzke C, Christ GJ, Stief CG, Andersson KE, Hedlund P. Localization and function of cannabinoid receptors in the corpus cavernosum: basis for modulation of nitric oxide synthase nerve activity. Eur Urol. 2010;57(2):342–8.

    CAS  PubMed  Google Scholar 

  73. 73.

    Melis MR, Succu S, Mascia MS, Sanna F, Melis T, Castelli MP, et al. The cannabinoid receptor antagonist SR-141716A induces penile erection in male rats: involvement of paraventricular glutamic acid and nitric oxide. Neuropharmacology. 2006;50(2):219–28.

    CAS  PubMed  Google Scholar 

  74. 74.

    Pizzol D, Demurtas J, Stubbs B, Soysal P, Mason C, Isik AT, et al. Relationship between cannabis use and erectile dysfunction: a systematic review and meta-analysis. Am J Mens Health. 2019;13(6):1557988319892464.

    PubMed  PubMed Central  Google Scholar 

  75. 75.

    • De Nunzio C, Roehrborn CG, Andersson KE, McVary KT. Erectile dysfunction and lower urinary tract symptoms. Eur Urol Focus. 2017;3(4-5):352–63. Excellent review of this topic.

    PubMed  Google Scholar 

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Correspondence to Granville L. Lloyd.

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Lloyd, G.L., Wiesen, B., Atwell, M. et al. Marijuana, Alcohol, and ED: Correlations with LUTS/BPH. Curr Urol Rep 22, 21 (2021). https://doi.org/10.1007/s11934-020-01031-9

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Keywords

  • BPH
  • Voiding
  • LUTS
  • Prostate
  • Marijuana
  • ED