Table 1.
Included study (design and results).
| Author | Year | Country | Study design | Study population | Age | Gender | Cannabinoid type | Study duration | Disease duration | EDSS | Disease type | Age at diagnosis | NRS: numeric rating scale for spasticity | Modified Ashworth Scale | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Before | After | Before | After | |||||||||||||
| Vecchio et al. 15 | 2020 | Italy | Nonrandomized trial | 15 | 55.5 ± 5.2 | 11 F, 4 M | Nabiximols | 6 weeks | 17.4 ± 6.2 | Median (range) 6 (2–8) |
All progressive | Median (range) 5 (1–10) |
Median (range) 2 (0–8) |
Median (range) 14 (4–32) |
Median (range) 4 (1–16) |
|
| Koehler et al. 16 | 2013 | Germany | Observational study | 166 | 69 F, 97 M | Nabiximols | 9 months | 133 SPMS, 20 PPMS, 13 RRMS | Mean (range) 7 (4–10) (N = 120) |
Mean (range) 3 (0–6) (N = 120) |
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| Collin et al. 17 | 2010 | UK | Double-blind, randomized, placebo-controlled, parallel-group study | 337 (experiment: 167/control: 170) | Experiment: 48 ± 10.06/Control: 47.1 ± 10.15 | Experiment: 106 F, 61 M/control: 101 F, 69 M | Nabiximols | 15 weeks | Experiment: 14.4 ± 8.29/ control: 16 ± 8.48 | Experiment: 6 ± 1.56/control: 6 ± 1.50 | Mean (SE) experiment: 6.77 (0.14) control: 6.49 (0.09) |
Mean (SE) experiment: week 2: 6.16 (0.10) week 4: 5.81 (0.14) week 6: 5.59 (0.18) week 8: 5.49 (0.14) week 10: 5.35 (0.15) week 12: 5.36 (0.18) week 14: 5.34 (0.18) control: week 2: 5.96 (0.09) week 4: 5.73 (0.14) week 6: 5.64 (0.14) week 8: 5.70 (0.14) week 10: 5.75 (0.16) week 12: 5.59 (0.15) week 14: 5.58 (0.13) | ||||
| Squintani et al. 18 | 2016 | Italy | Nonrandomized trial | 19 | 56.1 ± 8.9 | 14 F, 5 M | Nabiximols | 4 weeks | 17.6 ± 11.3 | 6.1 ± 1.4 | 1.1 ± 0.6 | 0.7 ± 0.5 | ||||
| Freidel et al. 19 | 2014 | Germany | Observational study | 33 | 48.1 | 21 F, 12 M | Nabiximols | 6 weeks | 4.6 | Mean, median (Q1, Q2,Q3, Q4) 6.03, 6 (3,5,7,10) |
Mean, median (Q1,Q2, Q3,Q4) 3.61, 3 (1,2,5,7) |
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| Marinelli et al. 20 | 2016 | Italy | Nonrandomized trial | 36 | 53.77 ± 10.32 | 21 F, 15 M | Nabiximols | 4 weeks | 181.28 ± 87.62 months | 6.83 ± 0.55 | 29 SPMS, 6 PPMS, 1 RRMS | 6.8 ± 1.7 | 5.7 ± 2.1 | |||
| Patti et al. 21 | 2015 | Italy | Cohort study | 1615 | 51 ± 9.5 | 849 F, 766 M | Nabiximols | 24 weeks | 17.5 ± 8.6 | Median (range) 6.5 (1.5–9.5) |
7.5 ± 1.4 (N = 1597) | Week 4: 5.9 ± 1.6 (N = 1432) week 12: 5.1 ± 1.6 (N = 889) week 24: 4.8 ± 1.7 (N = 593) |
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| Vaney et al. 22 | 2004 | Switzerland | Randomized, double-blind, placebo-controlled cross-over parallel group study | 57 | 54.9 ± 10 | 29 F, 28 M | Cannabis extract | 31 days (14 treatment, 3 washout, 14 placebo) | 17 ± 8.4 | Median 7 | Treatment period: 12.2 ± 6.4 Placebo period: 13.1 ± 6.3 (N = 50) |
Treatment period: 11.6 ± 6.5 Placebo period: 11.5 ± 6.1 (N = 50) |
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| Centonze et al. 23 | 2009 | Italy | Non randomized trial | 20 | 13 F, 7 M | Nabiximols | 6 weeks | 5.36 ± 1.69 | Week 1: 5.86 ± 1.98 Week 2: 5.85 ± 2.5 Week 3: 5.73 ± 2.48 Week 4: 5.56 ± 2.18 Week 5: 5.76 ± 2.1 Week 6: 5.71 ± 2.52 |
5.14 ± 2.12 | Week 1: 5.11 ± 2.12 Week 2: 4.91 ± 2.01 Week 3: 4.97 ± 1.94 Week 4: 4.94 ± 2.02 Week 5: 5.14 ± 1.97 Week 6: 4.91 ± 1.98 |
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| Paolicelli et al. 24 | 2016 | Italy | Cohort | 102 | 48.8 ± 10.4 | 52 F, 50 M | Nabiximols | 40 weeks | 19.2 ± 8 | 6.7 ± 1.1 | 59 SPMS, 25 RRMS, 10 PPMS, 8 PRMS | 8.7 ± 1.3 | Month 1: 6.2 ± 1.8 Month 3: 5.9 ± 1.6 Month 6: 6.1 ± 1.4 Year 1: 6.2 ± 1.4 |
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| Flachenecker et al. 25 | 2014 | Germany | Observational, prospective, multicenter, noninterventional study | 52 | 49.4 ± 8.6 | 29 F, 23 M | Nabiximols | 1 year | 14.1 ± 8.0 | Median (range) 6 (3–8) |
34 SPMS, 10 RRMS, 8 PPMS | 6.2 ± 1.8 | 4.6 ± 2.1 (N = 51) | |||
| Flachenecker et al. 26 | 2014 | Germany | Observational, prospective, multicenter, noninterventional study | 276 | 50.0 ± 9.4 | 168 F, 108 M | Nabiximols | 3 months | 15.4 ± 9.0 | Median (range) 6 (1–9) |
168 SPMS, 72 RRMS, 34 PPMS, 2 PRMS | 6.1 ± 1.7 | Week 4: 5.2 ± 1.9 (N = 210) | 3.0 ± 0.8 | Week 4: 2.7 ± 0.9 (N = 260) Week 12: 2.6 ± 1.0 (N = 95) |
|
| Sartori et al. 27 | 2021 | Italy | Retrospective single-center study | 36 | 53.9 ± 8.7 | 18 F, 18 M | Nabiximols | Median (range) 178 (8−447) months |
Median (range) 6.75 (2.5−9) |
19 SPMS, 9 RRMS, 8 PPMS | Median (range) 2 (0–4) |
Median (range) 2 (0–4) |
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| Chisari et al. 28 | 2020 | Italy | Prospective observational multicenter | 1845 | 50.9 ± 12.3 | 1226 F, 619 M | Nabixomols | 18 months | 16.3 ± 8.8 | Median (Range) 6.5 (4–8.5) |
1283 SPMS, 333 PPMS, 229 RRMS | 35.9 ± 11.7 | 7.8 ± 1.7 | Week 4: 5.7 ± 1.6 (N = 1502) Month 3: 5.2 ± 1.4 (N = 1241) Month 6: 5.0 ± 1.7 (N = 1017) Month 12: 4.8 ± 1.8 (N = 853) Month 18: 4.7 ± 2.0 (N = 777) |
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| Lus et al. 29 | 2018 | Italy | Open-label, prospective, multicenter, nonpharmacological, randomized, minor interventional, postmarketing authorization pilot project | 52 | 51.9 ± 9.1 | 32 F, 20 M | Nabiximols (chewing gum, cold bottle) | 4 weeks | 13.2 ± 7.5 | 6.2 ± 1.4 | 27 SPMS, 12 RRMS, 11 PPMS, 2 PRMS | 6.1 ± 2.2 | 5.4 ± 2.2 (N = 46) | |||
| Novotna et al. 30 | 2011 | UK | Nonrandomized trial | 331 | 49.1 ± 9.85 | 202 F, 129 M | Nabiximols | 4 weeks | 12.3 ± 7.49 | 6 ± 1.4 | 6.91 ± 1.25 | 3.9 ± 1.51 | ||||
| Gustavsen et al. 31 | 2020 | Denmark | Observational study | 28 (24 THC, 4 CBD) | 50 | 21 F, 7 M | Cannabis oil (THC rich, CBD rich) | 4 weeks | Median (range) 11 (1–28) | Median (range) 4.5 (2–9) |
15 RRMS, 8 SPMS, 5 PPMS | Median (range) THC: 6 (1–10) CBD: 6 (4–8) |
Median (range) THC: 2.5 (0–7) (N = 18) CBD: 2 (2–2) (N = 3) |
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| D’hooghe et al. 32 | 2021 | Belgium | Retrospective study | 238 | Nabiximols | 12 weeks | 8.1 ± 1.08 | Week 4: 5.2 ± 1.85 (N = 229) Week 8: 4.6 ± 1.69 (N = 188) Week 12: 4.1 ± 1.78 (N = 96) |
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| Messina et al. 33 | 2017 | Italy | Observational study | 1597 | 51 | 841 F, 756 M | Nabiximols | 6 months | 17.5 ± 8.6 | Median (range) 6.5 (1.5–9.5) |
1029 SPMS, 311 RRMS, 255 PPMS | 7.5 ± 1.4 | Month 1: 5.9 ± 1.6 Month 3: 5.1 ± 1.6 Month 6: 4.8 ± 1.7 |
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| Serpell et al. 34 | 2012 | UK | Open-label trial | 146 | 50 ± 9 | 94 F, 52 M | Nabiximols | 52 weeks | Mean (SEM) 5.68 (0.22) |
Mean (SEM) 3.85 (0.25) |
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| Corey-Bloom et al. 35 | 2012 | USA | Randomized, double-blind, placebo-controlled crossover design | 30 | 51 ± 8 | 19 F, 11 M | Smoked cannabis | 2 weeks | 8.5 ± 7.4 | 5.3 ± 1.5 | 20 SPMS, 10 RRMS | Mean (95%CI) treatment: 9.13 (8.21–10.07) placebo: 8.92 (8.03–9.79) |
Mean (95%CI) treatment: 6.18 (5.13–7.21) placebo: 8.71 (7.57–9.71) |
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| Vermersch et al. 36 | 2016 | Italy | Observational study | 433 | 50.4 ± 10.4 | 239 F, 194 M | Nabiximols | 3 months | 13.7 ± 7.9 | 5.94 ± 1.38 | 223 RRMS, 137 RRMS, 72 PPMS | 6.9 ± 1.9 (N = 394) | 5.3 ± 1.8 (N = 253) | |||
| Maniscalco et al. 37 | 2017 | Italy | Observational study | 15 | 56.1 ± 8.6 | 7 F, 8 M | Nabiximols | 4 weeks | Median (range) 91 (4–276) months | Median (range) 8 (4–10) |
Median (range) 6 (2–8) |
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| Carotenuto et al. 38 | 2016 | US | Nonrandomized trial | 10 | 51.10 ± 9.96 | 10 F, 10 M | Nabiximols | 1 year | Median (range) 9.21 (2–39) | 4.70 ± 1.08 | 12 progressive, 8 relapsing | 37.28 ± 13.61 | 8 ± 1.93 (N = 10) | 5.50 ± 2.45 (N = 10) | ||
| Coghe et al. 39 | 2015 | Italy | Nonrandomized trial | 20 | 49.6 ± 9.11 | 11 F, 9 M | Nabiximol | 1 month | 5.3 ± 0.81 | 4 RRMS, 1 PRMS, 1 SPMS | 7.1 ± 1.22 | 5.24 ± 1.39 | ||||
| Ferrante et al. 40 | 2019 | Italy | Retrospective cohort study | 37 | 56 ± 9 | 26 F, 11 M | Nabiximols | 7.86 ± 1.00 | 5.66 ± 1.04 | |||||||
| Patti et al. 41 | 2022 | Italy | Observational study | 1138 | 51.5 ± 9.8 | 621 F, 517 M | Nabiximols | 18 month | 19.8 ± 10.5 | 6.5 ± 1.16 | 761 SPMS, 193 RRMS, 183 PPMS | 7.8 ± 1.25 | Week 4: 5.9 ± 1.5 Month 3: 5.3 ± 1.3 (N = 760)Month 6: 5.1 ± 1.2 (N = 653) Month 12: 5.1 ± 1.2 (N = 473) Month 18: 5.1 ± 1.2 (N = 397) | |||
| Pau et al. 42 | 2023 | Italy | Nonrandomized trial | 13 | 51.2 ± 11.8 | 9 F, 4 M | Nabixiomols | 4 weeks | 5.4 ± 1.6 | 11 SPMS, 1 RRMS, 1 PPMS | 6.3 ± 1.3 | 4.2 ± 1.3 | ||||
| Guger et al. 43 | 2023 | Austria | Prospective observational study | 55 | 52.5 ± 9.6 | 33 F, 22 M | Nabiximols | 3 month | 15.1 ± 9.1 | 5.3 ± 1.3 | 28 SPMS, 18 PPMS, 9 RRMS | 6.4 ± 1.8 | Month 1: 4.8 ± 1.7 (N = 43) Month 3: 3.9 ± 2.0 (N = 40) |
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| Gajofatto et al. 44 | 2023 | Italy | Nonrandomized trial | 12 | Median (range) 51 (36–73) |
5 F, 7 M | Nabiximols | 8 weeks | Median (range) 21.5 (10–37) |
Median (range) 6 (4.5–8) |
10 SPMS, 2 RRMS | Median (range) 8 (5–9) |
Median (range) 6.5(4–8) |
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| Killestein et al. 45 | 2002 | The Netherland | Randomized, double-blind, placebo-controlled, twofold crossover study | 16 (each group 8) | 46 ± 7.9 | Dronabinol | 4 weeks | 15 ± 10.7 | 6.2 ± 1.2 | 10 SPMS, 6 PPMS | Placebo: 1.15 (0.94–1.37) plant extract: 1.20 (0.97–1.39) drobinidol: 1.13 (0.92–1.36) | Placebo: 1.03 (0.81–1.23) plant extract: 0.94 (0.74–1.14) drobinidol: 0.97 (0.77–1.18) | ||||
CBD: cannabidiol; EDSS: Expanded Disability Status Scale; F: female; M, male; NRS: Numeric Rating Scale; PPMS: primary progressive multiple sclerosis; PRMS: progressive-relapsing multiple sclerosis; RRMS: relapsing-remitting mustiple sclerosis; SE: standard error; SEM: standard error of the mean; SPMS: slowly progressive multiple sclerosis; THC: tetrahydrocannabinol.