Safety and tolerability of nabiximols oromucosal spray: a review of real-world experience in observational studies, registries, and case reports

References

• Russo E, Guy GW. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Med Hypotheses. 2006;66(2):234–246.
   PubMed Web of Science ®Google Scholar
• Sativex oromucosal spray. Summary of product characteristics; August 2020. GW Pharma Ltd. Available at: https://www.medicines.org.uk/emc/product/602/smpc#gref [Accessed 2020 Oct 9].
   Google Scholar
• Sativex® oromucosal spray. Summary of product characteristics; September 2012. Neopharm Scientific Ltd. Available at: http://www.pharmaline.co.il/images/newsletterregistration/neopharm/2012/03092012/sativex_dr.pdf [Accessed 2020 Oct 9].
   Google Scholar
• Häuser W, Finn DP, Kalso E, et al. European pain federation (EFIC) position paper on appropriate use of cannabis-based medicines and medical cannabis for chronic pain management. Eur J Pain. 2018;22(9):1547–1564. .
   PubMed Web of Science ®Google Scholar
• Prieto González JM, Vila Silván C. Safety and tolerability of nabiximols oromucosal spray: a review of more than 15 years’ accumulated evidence from clinical trials. Expert Rev Neurother. 2021. submitted.
   PubMedGoogle Scholar
• Trojano M, Celius EG, Donzé C, et al. Clinical case reviews and poster sessions in multiple sclerosis spasticity: main outcomes and highlights. Eur Neurol. 2014;72(Suppl s1):15–19.
   PubMedGoogle Scholar
• Coghe G, Pau M, Corona F, et al. Walking improvements with nabiximols in patients with multiple sclerosis. J Neurol. 2015;262(11):2472–2477.
   PubMed Web of Science ®Google Scholar
• Illomei G, Spinicci G, Locci E, et al. Muscle elastography: a new imaging technique for multiple sclerosis spasticity measurement. Neurol Sci. 2017;38(3):433–439.
   PubMed Web of Science ®Google Scholar
• Mallada Frechín J. Effect of tetrahydrocannabinol: cannabidioloromucosal spray on activities of daily living in multiple sclerosis patients with resistant spasticity: a retrospective, observational study. Neurodegener Dis Manag. 2018;8(3):151–159.
   PubMed Web of Science ®Google Scholar
• Sorosina M, Clarelli F, Ferrè L, et al. Clinical response to nabiximols correlates with the downregulation of immune pathways in multiple sclerosis. Eur J Neurol. 2018;25(7):934–e70.
   PubMed Web of Science ®Google Scholar
• Meyer T, Funke A, Münch C, et al. Real world experience of patients with amyotrophic lateral sclerosis (ALS) in the treatment of spasticity using tetrahydrocannabinol: cannabidiol(THC:CBD). BMC Neurol. 2019;19(1):222.
   PubMed Web of Science ®Google Scholar
• Selvarajah D, Gandhi R, Emery CJ, et al. Randomized placebo-controlled double-blind clinical trial of cannabis-based medicinal product (Sativex) in painful diabetic neuropathy: depression is a major confounding factor. Diabetes Care. 2010;33(1):128–130.
   PubMed Web of Science ®Google Scholar
• Flachenecker P, Henze T, Zettl UK. 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. 2014;71:271–279.
   PubMed Web of Science ®Google Scholar
• Flachenecker P, Henze T, Zettl UK. Long-term effectiveness and safety of nabiximols (tetrahydrocannabinol/cannabidiol oromucosal spray) in clinical practice. Eur Neurol. 2014;72(1–2): 95–102. .
   PubMed Web of Science ®Google Scholar
• Lorente Fernández L, Monte Boquet E, Pérez-Miralles F, et al. Clinical experiences with cannabinoids in spasticity management in multiple sclerosis. Neurologia. 2014;29(5):257–260.
   PubMed Web of Science ®Google Scholar
• Koehler J, Feneberg W, Meier M, et al. Clinical experience with THC:CBD oromucosal spray in patients with multiple sclerosis-related spasticity. Int J Neurosci. 2014;124(9):652–656.
   PubMed Web of Science ®Google Scholar
• Freidel M, Tiel-Wilck K, Schreiber H, et al. Drug-resistant MS spasticity treatment with Sativex ® add-on and driving ability. Acta Neurol Scand. 2015;131(1):9–16.
   PubMed Web of Science ®Google Scholar
• Oreja-Guevara C, Casanova B, Ordás CM, et al. Observational safety study of THC:CBD oromucosal spray (Sativex) in multiple sclerosis patients with spasticity. Clin Exp Pharmacol. 2015;5:5.
   Google Scholar
• Etges T, Karolia K, Grint T, et al. An observational postmarketing safety registry of patients in the UK, Germany, and Switzerland who have been prescribed Sativex® (THC:CBD, nabiximols) oromucosal spray. Ther Clin Risk Manag. 2016;12:1667–1675.
   PubMed Web of Science ®Google Scholar
• Marinelli L, Mori L, Canneva S, et al. The effect of cannabinoids on the stretch reflex in multiple sclerosis spasticity. Int Clin Psychopharmacol. 2016;31(4):232–239.
   PubMed Web of Science ®Google Scholar
• Paolicelli D, Direnzo V, Manni A, et al. Long-term data of efficacy, safety, and tolerability in a real-life setting of THC/CBD oromucosal spray-treated multiple sclerosis patients. J Clin Pharmacol. 2016;56(7):845–851.
   PubMed Web of Science ®Google Scholar
• Vermersch P, Trojano M. Tetrahydrocannabinol:cannabidioloromucosal spray for multiple sclerosis-related resistant spasticity in daily practice. Eur Neurol. 2016;76(5–6):216–226.
   PubMed Web of Science ®Google Scholar
• Messina S, Solaro C, Righini I, et al. Sativex in resistant multiple sclerosis spasticity: discontinuation study in a large population of Italian patients (SA.FE study). PLoS One. 2017;12(8):e0180651. .
   PubMed Web of Science ®Google Scholar
• Carotenuto A, Iodice R, Petracca M, et al. Upper motor neuron evaluation in multiple sclerosis patients treated with Sativex®. Acta Neurol Scand. 2017;135(4):442–448.
   PubMed Web of Science ®Google Scholar
• Castelli L, Prosperini L, Pozzilli C. Balance worsening associated with nabiximols in multiple sclerosis. Mult Scler. 2019;25(1):113–117.
   PubMed Web of Science ®Google Scholar
• Grimaldi AE, De Giglio L, Haggiag S, et al. The influence of physiotherapy intervention on patients with multiple sclerosis-related spasticity treated with nabiximols (THC:CBD oromucosal spray). PLoS One. 2019;14(7):e0219670.
   PubMed Web of Science ®Google Scholar
• Koehler J, Amato MP, Oreja-Guevara C, et al. Clinical case reviews in multiple sclerosis spasticity: experiences from around Europe. Expert Rev Neurother. 2013;13(sup2):61–66.
   PubMed Web of Science ®Google Scholar
• Stroet A, Trampe N, Chan A. Treatment failure of intrathecal baclofen and supra-additive effect of nabiximols in multiple sclerosis-related spasticity: a case report. Ther Adv Neurol Disord. 2013;6(3):199–203.
   PubMed Web of Science ®Google Scholar
• Koehler J. Who benefits most from THC:CBD spray? Learning from clinical experience. Eur Neurol. 2014;71(Suppl s1):10–15.
   PubMedGoogle Scholar
• Russo M, Rifici C, Sessa E, et al. Sativex-induced neurobehavioral effects: causal or concausal? A practical advice! Daru. 2015;23(1):25.
   PubMedGoogle Scholar
• Flachenecker P, Saccà F, Vila C. Variability of multiple sclerosis spasticity symptoms in response to THC:CBD oromucosal spray: tracking cases through clinical scales and video recordings. Case Rep Neurol. 2018;10(2):169–176.
   PubMed Web of Science ®Google Scholar
• Grao-Castellote C, Torralba-Collados F, Gonzalez LM, et al. [Delta-9-tetrahydrocannabinol-cannabidiol in the treatment of spasticity in chronic spinal cord injury: a clinical experience]. Rev Neurol. 2017;65(7):295–302. Spanish.
   PubMed Web of Science ®Google Scholar
• Trojano M, Vila C. Effectiveness and tolerability of THC/CBD oromucosal spray for multiple sclerosis spasticity in Italy: first data from a large observational study. Eur Neurol. 2015;74(3–4):178–185.
   PubMed Web of Science ®Google Scholar
• Patti F, Messina S, Solaro C, et al. Efficacy and safety of cannabinoid oromucosal spray for multiple sclerosis spasticity. J Neurol Neurosurg Psychiatry. 2016;87(9):944–951.
   PubMed Web of Science ®Google Scholar
• Scully C. Cannabis; adverse effects from an oromucosal spray. Br Dent J. 2007;203(6):E12.
   PubMedGoogle Scholar
• Morris J, Bond J, Taylor C. Results of an audit of ‘real-world’ patient-reported outcomes following a therapeutic trial of Sativex® for persistent non-cancer pain within a Jersey pain centre, local guideline adherent, self-selecting patient cohort. Pain News. 2019;17(3):154–159.
   Google Scholar
• Ueberall MA, Essner U, Mueller-Schwefe GH. Effectiveness and tolerability of THC:CBD oromucosal spray as add-on measure in patients with severe chronic pain: analysis of 12-week open-label real-world data provided by the German pain e-registry. J Pain Res. 2019;12:1577–1604.
   PubMed Web of Science ®Google Scholar
• Yang PT, Ong-Lam M. Case study: management of post-parotidectomy neuropathic pain with Sativex.UBC Med J. 2010;2(1):45–48.
   Google Scholar
• Wade D. Evaluation of the safety and tolerability profile of Sativex: is it reassuring enough?. Expert Rev Neurother 2012;12(4 Suppl):9–14.
   PubMedGoogle Scholar
• Lus G, Cantello R, Danni MC, et al. Palatability and oral cavity tolerability of THC:CBD oromucosal spray and possible improvement measures in multiple sclerosis patients with resistant spasticity: a pilot study. Neurodegener Dis Manag. 2018;8(2):105–113.
   PubMed Web of Science ®Google Scholar
• Torres-Moreno MC, Papaseit E, Torrens M, et al. Assessment of efficacy and tolerability of medicinal cannabinoids in patients with multiple sclerosis: a systematic review and meta-analysis. JAMA Network Open. 2018;1(6):e183485.
   PubMed Web of Science ®Google Scholar
• Braley TJ, Whibley D, Alschuler KN, et al. Cannabinoid use among Americans with MS: current trends and gaps in knowledge. Mult Scler J Exp Transl Clin. 2020;6(3):2055217320959816.
   Google Scholar
• Honarmand K, Tierney MC, O’Connor P, et al. Effects of cannabis on cognitive function in patients with multiple sclerosis. Neurology. 2011;76(13):1153–1160.
   PubMed Web of Science ®Google Scholar
• Vachová M, Novotná A, Mares J, et al. A multicentre, double-blind, randomised, parallel-group, placebo-controlled study of effect of long-term Sativex® treatment on cognition and mood of patients with spasticity due to multiple sclerosis. J Mult Scler. 2014;1:2.
   Google Scholar