Skip to main content

THC/CBD oromucosal spray in patients with multiple sclerosis overactive bladder: a pilot prospective study

Neurological Sciences volume 39, pages 97–102 (2018)Cite this article

Abstract

Lower urinary tract dysfunctions (LUTDs) are commonly reported in multiple sclerosis (MS) patients and are mainly related to neurogenic overactive bladder (OAB). The aim of this observational study was to assess the effect of a tetrahydrocannabinol-cannabidiol (THC/CBD) oromucosal spray on resistant OAB by means of clinical and instrumental tools. Twenty-one MS patients were screened, and 15 cases have been evaluated. They underwent a specific clinical assessment (overactive bladder symptom score, OABSS) and a urodynamic assessment evaluating the maximal cystometric capacity (CCmax), bladder compliance (Qmax), maximum detrusor pressure (Pdet max), detrusor pressure at the first desire (Pdet first), bladder volume at the first desire (BVFD), leakage volume (LV), and post-void residual volume (PVR), before and after 4 weeks of THC/CBD administration. A complete neurological evaluation, including the assessment of their spasticity using the Modified Ashworth Scale (MAS) and the spasticity 0–10 numerical rating scale (NRS), was performed at the same times. Mobility was evaluated through the 25-ft walking-time test (T25-WT). The THC/CBD treatment successfully reduced the OAB symptoms (p = 0.001). Regarding the urodynamic findings after the end of treatment, PVR was significantly reduced (p = 0.016). Regarding the urodynamic findings after the end of treatment, PVR was significantly reduced (p = 0.016), while BVFD and CCmax were increased although the difference was not statistically significant. THC/CBD oromucosal spray has shown to be effective in improving overactive bladder symptoms in MS patients demonstrating a favorable impact on detrusor overactivity.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price includes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Koldewijn EL, Hommes OR, Lemmens WA, Debruyne FM, van Kerrebroeck PE (1995) Relationship between lower urinary tract abnormalities and disease-related parameters in multiple sclerosis. J Urol 154(1):169–173

    CAS  Article  PubMed  Google Scholar 

  2. de Sèze M, Ruffion A, Denys P, Joseph PA, Perrouin-Verbe B, GENULF (2007) The neurogenic bladder in multiple sclerosis: review of the literature and proposal of management guidelines. Mult Scler 13(7):915–928. https://doi.org/10.1177/1352458506075651

    Article  PubMed  Google Scholar 

  3. Gallien P, Robineau S, Nicolas B, Le Bot MP, Brissot R, Verin M (1998) Vesicourethral dysfunction and urodynamic findings in multiple sclerosis: a study of 149 cases. Arch Phys Med Rehabil 79(3):255–257

    CAS  Article  PubMed  Google Scholar 

  4. Giannantoni A, Scivoletto G, Di Stasi SM, Grasso MG, Vespasiani G, Castellano V (1998) Urological dysfunctions and upper urinary tract involvement in multiple sclerosis patients. Neurourol Urodyn 17(2):89–98

    CAS  Article  PubMed  Google Scholar 

  5. Hinson JL, Boone TB (1996) Urodynamics and multiple sclerosis. Urol Clin North Am 23(3):475–481

    CAS  Article  PubMed  Google Scholar 

  6. Wein AJ, Rovner ES (2002) Definition and epidemiology of overactive bladder. Urology 60(5, Suppl 1):7–12

    Article  PubMed  Google Scholar 

  7. Harris CJ, Lemack GE (2016) Neurourologic dysfunction: evaluation, surveillance and therapy. Curr Opin Urol 26(4):290–294. https://doi.org/10.1097/MOU.0000000000000290

    Article  PubMed  Google Scholar 

  8. Zecca C, Riccitelli GC, Disanto G, Singh A, Digesu GA, Panicari L, Puccini F, Mattioli M, Tubaro A, Gobbi C (2016) Urinary incontinence in multiple sclerosis: prevalence, severity and impact on patients’ quality of life. Eur J Neurol 23(7):1228–1234. https://doi.org/10.1111/ene.13010

    CAS  Article  PubMed  Google Scholar 

  9. Ghezzi A, Carone R, Del Popolo G, Amato MP, Bertolotto A, Comola M, Del Carro U, Di Benedetto P, Giannantoni A, Lopes de Carvalho ML, Montanari E, Patti F, Protti A, Rasia S, Salonia A, Scandellari C, Sperli F, Spinelli M, Solaro C, Uccelli A, Zaffaroni M, Zipoli V, Multiple Sclerosis Study Group, Italian Society of Neurology (2011) Recommendations for the management of urinary disorders in multiple sclerosis: a consensus of the Italian multiple sclerosis study group. Neurol Sci 32(6):1223–1231. https://doi.org/10.1111/ene.13010

    CAS  Article  PubMed  Google Scholar 

  10. Beard S, Hunn A, Wight J (2003) Treatments for spasticity and pain in multiple sclerosis: a systematic review. Health Technol Assess 7(40):iii ix-x,1–111

    CAS  Article  PubMed  Google Scholar 

  11. Novotna A, Mares J, Ratcliffe S, Novakova I, Vachova M, Zapletalova O, Gasperini C, Pozzilli C, Cefaro L, Comi G, Rossi P, Ambler Z, Stelmasiak Z, Erdmann A, Montalban X, Klimek A, Davies P, Sativex Spasticity Study Group (2011) A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex(®) ), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur J Neurol 18(9):1122–1231. https://doi.org/10.1111/j.1468-1331.2010.03328.x

    CAS  Article  PubMed  Google Scholar 

  12. Russo E, Guy GW (2006) A tale of two cannabinoids: the therapeutic rationale for combining tetrahydro-cannabinol and cannabidiol. Med Hypotheses 66(2):234–246. https://doi.org/10.1016/j.mehy.2005.08.026

    CAS  Article  PubMed  Google Scholar 

  13. Martyn CN, Illis LS, Thom J (1995) Nabilone in the treatment of multiple sclerosis. Lancet 345(8949):579

    CAS  Article  PubMed  Google Scholar 

  14. Kavia RB, De Ridder D, Constantinescu CS, Stott CG, Fowler CJ (2010) Randomized controlled trial of Sativex to treat detrusor overactivity in multiple sclerosis. Mult Scler 16(11):1349–1359. https://doi.org/10.1177/1352458510378020

    CAS  Article  PubMed  Google Scholar 

  15. Brady CM, DasGupta R, Dalton C, Wiseman OJ, Berkley KJ, Fowler CJ (2004) An open-label pilot study of cannabis-based extracts for bladder dysfunction in advanced multiple sclerosis. Mult Scler 10(4):425–433. https://doi.org/10.1191/1352458504ms1063oa

    CAS  Article  PubMed  Google Scholar 

  16. Collin C, Ehler E, Waberzinek G, Alsindi Z, Davies P, Powell K, Notcutt W, O'Leary C, Ratcliffe S, Nováková I, Zapletalova O, Piková J, Ambler Z (2010) A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis. Neurol Res 32(5):451–459. https://doi.org/10.1179/016164109X12590518685660

    CAS  Article  PubMed  Google Scholar 

  17. Hedlund P (2014) Cannabinoids and the endocannabinoid system in lower urinary tract function and dysfunction. Neurourol Urodyn 33(1):46–53. https://doi.org/10.1002/nau.22442

    CAS  Article  PubMed  Google Scholar 

  18. Tyagi P, Tyagi V, Yoshimura N, Chancellor M (2010) Functional role of cannabinoid receptors in urinary bladder. Indian J Urol 26(1):26–35. https://doi.org/10.4103/0970-1591.60440

    Article  PubMed  PubMed Central  Google Scholar 

  19. Juszczak K, Maciukiewicz P (2015) The role of the peripheral cannabinoid system in the pathogenesis of detrusor overactivity evoked by increased intravesical osmolarity in rats. Can J Physiol Pharmacol 93(8):721–726

    CAS  Article  PubMed  Google Scholar 

  20. Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69(2):292–302. https://doi.org/10.1002/ana.22366

    Article  PubMed  PubMed Central  Google Scholar 

  21. Farrar JT, Troxel AB, Stott C, Duncombe P, Jensen MP (2008) Validity, reliability, and clinical importance of change in a 0-10 numeric rating scale measure of spasticity: a post hoc analysis of a randomized, double-blind, placebo-controlled trial. Clin Ther 30(5):974–985. https://doi.org/10.1016/j.clinthera.2008.05.011

    Article  PubMed  Google Scholar 

  22. Blaivas JG, Panagopoulos G, Weiss JP, Somaroo C (2007) Validation of the overactive bladder symptom score. J Urol 178(2):543–547. https://doi.org/10.1016/j.juro.2007.03.133

    Article  PubMed  Google Scholar 

  23. Kurtzke JF (2008) Historical and clinical perspectives of the expanded disability status scale. Neuroepidemiology 31(1):1–9. https://doi.org/10.1159/000136645

    Article  PubMed  Google Scholar 

  24. Bohannon RW, Smith MB (1987) Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther 67(2):206–207

    CAS  Article  PubMed  Google Scholar 

  25. Kaufman M, Moyer D, Norton J (2000) The significant change for the timed 25-foot walk in the multiple sclerosis functional composite. Mult Scler 6(4):286–290. https://doi.org/10.1177/135245850000600411

    CAS  Article  PubMed  Google Scholar 

  26. Schäfer W, Abrams P, Liao L, Mattiasson A, Pesce F, Spangberg A, Sterling AM, Zinner NR, van Kerrebroeck P, International Continence Society (2002) Good urodynamic practices: uroflowmetry, filling cystometry, and pressure-flow studies. Neurourol Urodyn 21(3):261–274

    Article  PubMed  Google Scholar 

  27. Flachenecker P, Henze T, Zettl UK (2014) Nabiximols (THC/CBD Oromucosal spray, Sativex ®) in clinical practice—results of a multicenter, non-interventional study (MOVE 2) in patients with multiple sclerosis spasticity. Eur Neurol 71:173–181. https://doi.org/10.1159/000357427

    Article  Google Scholar 

  28. Patti F, Messina S, Solaro C, Amato MP, Bergamaschi R, Bonavita S, Bruno Bossio R, Brescia Morra V, Costantino GF, Cavalla P, Centonze D, Comi G, Cottone S, Danni M, Francia A, Gajofatto A, Gasperini C, Ghezzi A, Iudice A, Lus G, Maniscalco GT, Marrosu MG, Matta M, Mirabella M, Montanari E, Pozzilli C, Rovaris M, Sessa E, Spitaleri D, Trojano M, Valentino P, Zappia M, on behalf of the SA.FE. study group (2016) Efficacy and safety of cannabinoid oromucosal spray for multiple sclerosis spasticity. J Neurol Neurosurg Psychiatry 87(9):944–951. https://doi.org/10.1136/jnnp-2015-312591

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. Vermersch P, Trojano M (2016) Tetrahydrocannabinol:cannabidiol oromucosal spray for multiple sclerosis-related resistant spasticity in daily practice. Eur Neurol 76:216–226. https://doi.org/10.1159/000449413

    CAS  Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Multiple Sclerosis Center “A Cardarelli” Hospital, Via “A Cardarelli” n.9, Naples, Italy

    Giorgia Teresa Maniscalco, G. Guarcello, O. Moreggia & C. Florio

  2. Neurological Clinic “A. Cardarelli” Hospital, Via “A.Cardarelli” n.9, Naples, Italy

    Giorgia Teresa Maniscalco, V. Manzo, M. Napolitano & C. Florio

  3. Urological Clinic of “A. Cardarelli” Hospital, Via “A.Cardarelli” n.9, Naples, Italy

    R. Aponte & F. Chiariello

  4. Department of Public Health, University of Naples “Federico II”, Via Sergio Pansini, Naples, Italy

    D. Bruzzese

Authors
  1. Giorgia Teresa Maniscalco
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Aponte
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Bruzzese
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Guarcello
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. V. Manzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Napolitano
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. O. Moreggia
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. F. Chiariello
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. C. Florio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giorgia Teresa Maniscalco.

Ethics declarations

Conflicts of interest

Giorgia Teresa Maniscalco received personal compensation from Novartis, Genzyme, Biogen, Merck Serono, and TEVA for public speaking and advisory boards.

Roberto Aponte does not have disclosures.

Dario Bruzzese does not have disclosures.

Giovanni Guarcello does not have disclosures.

Massimo Napolitano does not have disclosures.

Valentino Manzo does not have disclosures.

Ornella Moreggia does not have disclosures.

Francesco Chiariello does not have disclosure.

Ciro Florio received personal compensation from Merk Serono, Biogen, and TEVA for public speaking and advisory boards.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Maniscalco, G.T., Aponte, R., Bruzzese, D. et al. THC/CBD oromucosal spray in patients with multiple sclerosis overactive bladder: a pilot prospective study. Neurol Sci 39, 97–102 (2018). https://doi.org/10.1007/s10072-017-3148-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-017-3148-6

Keywords

  • Multiple sclerosis
  • Spasticity
  • Cannabinoids
  • Nabiximols
  • Sativex
  • LUTDs