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. 2023 Jul 28;16(8):1079.
doi: 10.3390/ph16081079.

Cannabis-Based Medicine for Neuropathic Pain and Spasticity-A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial

Julie Schjødtz Hansen  1   2 , Stefan Gustavsen  3 , Homayoun Roshanisefat  4 , Matthias Kant  5   6 , Fin Biering-Sørensen  7 , Claus Andersen  7 , Anna Olsson  3 , Helene Højsgaard Chow  3 , Nasrin Asgari  4   8 , Julie Richter Hansen  3   9 , Helle Hvilsted Nielsen  10 , Rikke Middelhede Hansen  11 , Thor Petersen  12 , Annette Bang Oturai  3 , Finn Sellebjerg  3 , Eva Aggerholm Sædder  13 , Helge Kasch  1   2 , Peter Vestergaard Rasmussen  1 , Nanna Brix Finnerup  1   2   14 , Kristina Bacher Svendsen  1   2
Affiliations

Cannabis-Based Medicine for Neuropathic Pain and Spasticity-A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial

Julie Schjødtz Hansen et al. Pharmaceuticals (Basel). .

Abstract

Patients with multiple sclerosis (MS) and spinal cord injury (SCI) commonly sustain central neuropathic pain (NP) and spasticity. Despite a lack of consistent evidence, cannabis-based medicine (CBM) has been suggested as a supplement treatment. We aimed to investigate the effect of CBM on NP and spasticity in patients with MS or SCI. We performed a randomized, double-blinded, placebo-controlled trial in Denmark. Patients aged ≥18 years with NP (intensity >3, ≤9 on a numerical rating scale (NRS0-10) and/or spasticity (>3 on NRS0-10) were randomized to treatment consisting of either delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), a combination of THC&CBD in maximum doses of 22.5 mg, 45 mg and 22.5/45 mg per day, respectively, or placebo. A baseline registration was performed before randomization. Treatment duration was six weeks followed by a one-week phaseout. Primary endpoints were the intensity of patient-reported NP and/or spasticity. Between February 2019 and December 2021, 134 patients were randomized (MS n = 119, SCI n = 15), where 32 were assigned to THC, 31 to CBD, 31 to THC&CBD, and 40 to placebo. No significant difference was found for: mean pain intensity (THC 0.42 (-0.54-1.38), CBD 0.45 (-0.47-1.38) and THC&CBD 0.16 (-0.75-1.08)), mean spasticity intensity (THC 0.24 (-0.67-1.45), CBD 0.46 (-0.74-1.65), and THC&CBD 0.10 (-1.18-1.39), secondary outcomes (patient global impression of change and quality of life), or any tertiary outcomes. We aimed to include 448 patients in the trial; however, due to COVID-19 and recruitment challenges, fewer were included. Nevertheless, in this four-arm parallel trial, no effect was found between placebo and active treatment with THC or CBD alone or in combination on NP or spasticity in patients with either MS or SCI. The trial was registered with the EU Clinical Trials Register EudraCT (2018-002315-98).

Keywords: cannabidiol (CBD); cannabis-based medicine (CBM); delta-9-tetrahydrocannabinol (THC); neuropathic pain (NP); spasticity.

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Conflict of interest statement

J.S.H., J.R.H., C.A., M.K., H.R., A.O., H.H.N., E.A.S., N.A. and F.B.-S. declare no conflicts of interest. S.G. has received support for congress participation from Merck. H.K. has served on scientific advisory boards for Lundbeck A/S and Novartis and has received travel grants from IPSEN and Merck. K.B.S. has served as a consultant for Takeda Pharma A/S and received travel grants from TEVA, Biogen, Merck, and Novartis. N.B.F. has received consultancy fees from Almirall, NeuroPN, Vertex, Nanobiotix, and Novartis Pharma, and has undertaken consultancy work for Aarhus University with remunerated work for Biogen, Merz, and Confo Therapeutics. She has received grants from IMI2PainCare, an EU IMI 2 (Innovative Medicines Initiative) public-private consortium, and the companies involved are Grunenthal, Bayer, Eli Lilly, Esteve, and Teva. P.V.R. has received speaker honoraria from Biogen, Roche, Merck, Alexion, and Novartis; support for congress participation from Merck, Roche, and Sanofi; and fees for serving on advisory boards from Bristol–Myers–Squibb, Merck, Roche, Novartis, Biogen, Sanofi, and Alexion. H.H.C. reports non-financial support from Merck, non-financial support from Teva, non-financial support from Biogen, and non-financial support from Roche, outside the submitted work. F.S. has served on scientific advisory boards, as a consultant for, supported congress participation, or received speaker honoraria from Alexion, Biogen, Bristol–Myers–Squibb, H. Lundbeck A/S, Merck, Novartis, Roche, and Sanofi Genzyme. His laboratory has received research support from Biogen, Merck, Novartis, Roche, and Sanofi Genzyme. RMH has received support for congress participation from Merck, Ipsen, and speaker honoraria from AbbVie. ABO has served on scientific advisory boards for Biogen Idec, Novartis, and Sanofi Genzyme; has received research support from Novartis; has received speaker honoraria from Biogen, Novartis, and TEVA; and has received support for congress participation from Merck, TEVA, Biogen, Roche, Novartis, and Sanofi Genzyme. T.P. has received research support for the MS clinic at Aarhus University Hospital from Merck, Alexion, Roche, Biogen, Novartis, and Sanofi.

Figures

Figure 1
Figure 1
CONSORT flow diagram. Flow diagram for the trial. MS: multiple sclerosis, SCI: spinal cord injury, THC: delta-9-tetrahydrocannabinol, CBD: cannabidiol, THC&CBD: delta-9-tetrahydrocannabinol and cannabidiol. AE: adverse event, ITT: intention to treat, PP: per protocol.
Figure 2
Figure 2
Patient Global Impression of Change. Patient Global Impression of Change (Kruskal–Wallis p-value = 0.82). THC: delta-9-tetrahydrocannabinol, CBD: cannabidiol, THC&CBD: delta-9-tetrahydrocannabinol and cannabidiol.
See this image and copyright information in PMC

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