Spasticity

Moderate evidence for chronic pain and spasticity, low evidence for nausea/vomiting, weight gain and sleep disorders; increased risk of side effects.

Comprehensive SR across 79 RCTs (n=6.462) on medical cannabis; moderate evidence for MS spasticity (nabiximols: OR=1.76 for subjective improvement, p0.001), chronic pain and chemotherapy-induced nausea; weak evidence for weight gain in HIV/AIDS.

Cannabinoids and botulinum toxin showed better efficacy than placebo for spasticity due to multiple sclerosis, but cannabinoids and tizanidine caused significantly more mild adverse effects than placebo.

Network meta-analysis of k=23 RCTs (n=2.720) on spasticity therapies in multiple sclerosis. Cannabinoids and botulinum toxin showed significantly better efficacy vs. placebo in the percentage of improved patients. Botulinum toxin superior vs. tizanidine and baclofen. SUCRA ranking recommends botulinum toxin as the optimal intervention, cannabinoids and TENS as alternatives worth considering.

Cannabinoids showed no statistically significant benefit for spasticity or spasm frequency, but markedly increased side effects such as dizziness, somnolence and nausea.

Systematic review and meta-analysis of cannabinoids for spasticity (MS or paraplegia); k=16 RCTs, n=2597 patients. Moderate evidence quality: non-significant spasticity reduction (SMD 0,36 [95% CI -0,17 to 0,88; p=0,18; I²=88%]), no significant change in spasm frequency (SMD 0,04 [95% CI -0,15 to 0,22]). Increased adverse event rates: dizziness (RR 3,45 [95% CI 2,71–4,4]), somnolence (RR 2,9 [95% CI 1,98–4,23]), nausea (RR 2,25 [95% CI 1,62–3,13]).

Nabiximols as add-on therapy leads to significantly higher responder rates in treatment-refractory MS spasticity compared to placebo (OR 2,41, 95% CI 1,39-4,18).

k=7 RCTs (n=1.128 MS patients with refractory spasticity); nabiximols (add-on) vs. placebo: NRS responder rate OR 2,41 (95%-CI 1,39–4,18); secondary outcomes consistent; Cochrane RoB2: at least some concerns regarding risk of bias.

Nabiximols showed a statistically significant reduction in spasticity versus placebo with a difference of -0,32 points on the numeric rating scale (p=0,026) and a higher responder rate (OR 1,62, p=0,0073).

Meta-analysis of 3 placebo-controlled RCTs (n=666 MS patients with spasticity): nabiximols (Sativex) reduced the spasticity NRS significantly more than placebo (difference −0,32; 95% CI −0,61 to −0,04; p=0,026). Significantly more patients achieved a ≥30% improvement (OR=1,62; 95% CI 1,15–2,28; p=0,0073). Tolerability good; serious adverse events under active treatment rare and reversible.

Cannabinoids show modest efficacy for spasticity in adults with multiple sclerosis, but limited evidence in other conditions and insufficient evidence in pediatric populations.

Systematic review on cannabinoids for spasticity; k=32 studies (adults and pediatrics). Evidence from RCTs: cannabinoids more effective than placebo for spasticity symptoms in adults with MS; predominantly patient-reported (not clinically assessed) outcomes, moderate effect size. Narrow therapeutic window and side effects to be considered. Few studies on other causes of spasticity; pediatric evidence insufficient for clinical practice.

THC:CBD spray showed improvements in spasticity of up to 45% and improved quality of life in MS patients with treatment-resistant spasticity.

Systematic review of cannabinoids in treatment-resistant MS spasticity (Jan 2017–May 2022), k=5 studies of medium to high quality, all evaluating THC:CBD spray. Improvement in spasticity scores up to 45%, significant increase in activities of daily living and quality of life, reduction of spasticity-associated symptoms. Average dose 5-7 sprays/day. Discontinuation rate ~40% (ineffectiveness and adverse effects). Adverse effect incidence ~17%, mild to moderate, decreasing over the course.

Sativex showed significant reduction of pain intensity and spasticity as well as modest but significant improvement in disability in MS patients.

Systematic review and meta-analysis on Sativex® in MS spasticity; k=20 studies according to PRISMA criteria. Significant reduction in spasticity (SMC: -1.29, 95% CI -1.63 to -0.94, p<0.0001). Additionally, pain reduction (NRS SMC: -0.88, 95% CI -1.20 to -0.57, p<0.0001) and moderate improvement in disability (EDSS SMC: -0.17, 95% CI -0.28 to -0.07, p=0.0015). Sativex® as an effective option for MS spasticity management.

Cannabis-based therapies showed clinically meaningful improvements in MS-related spasticity, especially over longer periods (MD 75,81 long-term vs. MD 4,53 short-term).

Systematic review + meta-analysis of k=9 RCTs (n=2544) on cannabis for MS spasticity (2003–2021). Pooled standardized MD=39.19 (95% CI: 34.32–44.05) for spasticity scores; subgroup analysis Ashworth scale MD=20.36 (95% CI: 20.35–20.37), NRS MD=1.18 (95% CI: 1.16–1.21). Long-term studies showed larger effects (MD=75.81, 95% CI: 66.39–85.22) vs. short-term studies (MD=4.53, 95% CI: -0.06–9.12). High heterogeneity (I²=100% overall, 91% NRS). Side effects mild (dizziness, dry mouth).

High evidence for cannabis benefit in MS spasticity and pain; low evidence for small effect in neuropathic pain; unclear evidence for nausea/vomiting in chemotherapy patients.

Systematic review on medical cannabis; k=41 RCTs (n=4.550), of which 15 studies on MS spasticity, 12 on chronic pain, 14 on chemotherapy-induced nausea/vomiting. Studies from 1975–2015, mostly European. Assessment according to Cochrane and GRADE methodology on efficacy and safety of cannabis (incl. extracts/tinctures) vs. placebo or other pharmacological agents.

No effect on the primary outcome (Ashworth scale for spasticity), but evidence for effects on patient-reported spasticity and pain as well as subjective improvement in mobility.

n=630 MS patients (33 UK centres, 15 weeks); primary endpoint (Ashworth scale) not met (p=0,40; difference cannabis extract vs. placebo: 0,32, 95% CI –1,04 to 1,67; THC vs. placebo: 0,94, 95% CI –0,44 to 2,31). Secondary, 61 % (cannabis extract), 60 % (THC) and 46 % (placebo) reported a subjective improvement in spasticity (p=0,003); objective improvement in mobility demonstrated.

Nabiximols led to significant improvements in spasticity versus placebo across all measured parameters (Spasticity NRS, Spasm Count, MAS) over 12 weeks.

Two enriched-responder RCTs (GWSP0604 + SAVANT), nabiximols vs. placebo in MS spasticity (NRS responders ≥20%). NRS reduction: -0,36 to -0,89 (GWSP0604) and -0,52 to -1,96 (SAVANT) versus placebo; spasm frequency reduced by 19–35%; MAS treatment difference lower extremities -0,16 to -0,37 (p significant at all measurement time points).

ITT analysis showed non-significant improvement; per-protocol population (79%) showed significant superiority of Sativex over placebo for NRS score and responder analyses.

n=337 MS patients with treatment-resistant spasticity (RCT, 15 weeks, double-blind, placebo-controlled). Sativex (nabiximols) showed in the per-protocol cohort (79% of participants) a significantly greater reduction in spasticity NRS than placebo (–1,3 vs. –0,8 points, p=0,035); responder rate (≥30% improvement) 36% vs. 24% (p=0,040). Secondary endpoints: Carer Global Impression of Change (p=0,013), timed 10-metre walk (p=0,042). The ITT primary endpoint narrowly missed statistical significance; PP analyses and responder analyses supported clinical efficacy.

Cannabis extract showed almost twice the muscle stiffness relief compared with placebo (29,4% vs. 15,7%; p=0,004).

MUSEC study: phase III RCT in n=279 MS patients (22 UK centres), oral cannabis extract (CE, n=144) vs. placebo (n=135) over 12 weeks (2-week titration 5–25 mg THC/day, 10 weeks maintenance). Primary endpoint muscle stiffness (Category Rating Scale): improvement rate 29.4% CE vs. 15.7% placebo (OR=2.26, 95% CI: 1.24–4.13, p=0.004 one-sided). Similar results at 4 and 8 weeks; secondary endpoints (pain, spasms, sleep quality) support the finding. Adverse effects consistent with the known cannabinoid profile.

Nabiximols showed a highly significant advantage over placebo in reducing spasticity (primary endpoint NRS, P=0,0002) as well as in all secondary endpoints (responder analysis, spasm frequency, sleep disturbance, global clinical impression).

n=241 (272/572 enrichment responders randomised), multicentre phase 3 RCT; nabiximols (Sativex) as add-on in MS spasticity patients not fully responding to standard therapy vs. placebo; primary endpoint NRS spasticity difference significant in favour of nabiximols (p=0,0002); secondary endpoints spasm frequency, sleep NRS and Global Impression of Change also significant.

THC:CBD spray showed significantly better improvement in MS spasticity compared with placebo (77,4% vs. 32,1% clinically relevant responders; p < 0,0001).

SAVANT study: n=191 MS patients with resistant spasticity, Phase A (4 weeks THC:CBD spray) → 106 responders randomised in Phase B (12 weeks double-blind). Primary endpoint: ≥30% NRS improvement significantly higher with THC:CBD vs. placebo (77,4% vs. 32,1%; p<0,0001). Secondary endpoints: mean spasticity NRS (p<0,0001), pain NRS (p=0,0013), modified Ashworth scale (p=0,0007) each significantly improved. Adverse effects mild/moderate with no new safety concerns.

The cannabis-based medicine showed significant superiority over placebo in the primary endpoint measurement (Numeric Rating Scale for spasticity, P=0,048) and resulted in a 40% responder rate with >30% improvement (P=0,014).

n=184, cannabis-based medicine (THC+CBD oromucosal) vs. placebo over 6 weeks; primary endpoint NRS spasticity significantly improved (P=0,048); 40% of patients achieved >30% benefit vs. placebo (P=0,014); Ashworth score and spasm frequency numerically favouring the active treatment.

Primary symptom (VAS) showed no significant difference between CBME and placebo, but spasticity VAS was reduced significantly more by CBME than placebo (P=0,001).

Multicenter RCT (n=160, MS patients with spasticity among other symptoms); CBME (THC/CBD, Sativex precursor) vs. placebo; spasticity VAS significantly reduced (p=0,001); primary overall symptom score n.s.; no cognitive side effects or relevant intoxication.

Nabiximols showed no significant difference from the placebo group in reducing spasticity on the 0-10 NRS after 12 weeks.

n=72 pediatric patients (8–18 years) with spasticity due to cerebral palsy/traumatic CNS injury, randomised 2:1 to oromucosal nabiximols (THC:CBD, max. 12 sprays/day) vs. placebo over 12 weeks. No significant difference in the primary endpoint (spasticity 0–10 NRS after 12 weeks). Generally well tolerated, but 3 cases of hallucinations reported (1 with suicide attempt).

Nabiximols led to an improvement in Modified Ashworth Scale scores of 0,11 points compared with a worsening of 0,16 points under placebo (p=0,013), with good tolerability.

n=59 (ALS/PLS), nabiximols vs. placebo over 6 weeks; Modified Ashworth Scale: nabiximols -0,11 vs. placebo +0,16 points, adjusted effect -0,32 (95% CI -0,57 to -0,07; p=0,013). Well tolerated, no serious adverse events.

No significant differences in spasticity, motor function and quality of life between FSCO and placebo; increased drowsiness in the FSCO group.

Double-blind RCT in n=53 children/adolescents (5-25 years) with spastic cerebral palsy GMFCS IV-V, Full-Spectrum Cannabis Oil (CBD:THC 10:1) vs. placebo over 6 weeks (followed by 6-week open-label phase); NO significant difference in spasticity (modified Ashworth Scale), motor function (GMFM-88) or quality of life between FSCO and placebo groups; significantly more drowsiness in the FSCO group; adverse events mild-moderate, no life-threatening events.

In the per-protocol population, significant improvement in spasm frequency and mobility, but no statistically significant effects in the ITT set.

n=50 MS patients with persistent spasticity (ITT), Cannabis sativa extract (THC 2,5 mg / CBD 0,9 mg per capsule, up to 30 mg THC/d) vs. placebo; in the per-protocol set (n=37) significant reduction of spasm frequency (p=0,013) and improved mobility after exclusion of falls (p=0,01); in the ITT set only trends without significance.

CBD did not significantly reduce spasticity, but significantly improved walking speed (T25-FW) and reduced pain more than placebo.

n=49 MS patients with spasticity-related gait disorders, randomized to purified CBD (5–80 mg/day) vs. placebo over 4 weeks. No significant reduction in spasticity severity between groups. T25-FW test duration decreased significantly more in the CBD group (p=0.031); maximum pain decreased significantly more (p=0.033).

Sativex showed significantly more frequent clinical improvement on the Modified Ashworth Scale (50% vs. 23,5%, p=0,041) compared to placebo, confirming the clinical benefit for MS spasticity.

n=34 progressive MS patients with spasticity (crossover RCT, 4 weeks), Sativex (THC+CBD) vs. placebo; primary endpoint H/M ratio showed no significant group difference; clinical response (modified Ashworth Scale ≥20% improvement) significantly more frequent under Sativex than placebo (50 vs. 23,5%; p=0,041).

Smoked cannabis reduced spasticity (Ashworth scale by 2,74 points more than placebo, p<0,0001) and pain significantly, but impaired cognition (PASAT score worsened by 8,67 points more, p=0,003).

RCT n=30 (of 37 randomised) multiple sclerosis spasticity, smoked cannabis (1x daily for 3 days) vs. placebo in crossover design. Modified Ashworth Scale reduction: -2,74 points vs. placebo (p<0,0001); VAS pain reduction: -5,28 points (p=0,008). Cognitive performance (PASAT) worsened (-8,67 points, p=0,003). No serious adverse effects.

Both cannabis extracts significantly reduced urinary incontinence, urgency and frequency as well as pain and spasticity.

n=15 MS patients with advanced disease; patient self-assessment of spasticity significantly improved under cannabis extracts (THC+CBD 2,5 mg/spray) (P<0,05, Wilcoxon). Spasticity was a measured secondary endpoint alongside pain and sleep; no separate scale specified.

Significant reduction in spasticity (NRS scores from median 6 to 3.5, p<0.001) with inverse correlation to THC/CBD plasma concentrations; no significant effects in motor tests.

n=12 MS patients with chronic THC/CBD oromucosal spray treatment, test dose 2 sprays at 15 min interval. Peak plasma concentrations: THC 0,60–13,29 ng/mL, CBD 0,55–11,93 ng/mL; time to peak: THC 150–240 min, CBD 90–240 min. Median NRS score decreased from 6 to 3,5 (p<0,001). Significant inverse correlation between intraindividual NRS scores and THC plasma concentrations (p<0,01) as well as CBD plasma concentrations (p<0,002).

Nabilone 1 mg daily led to significant reduction of spasticity-related pain (p < 0,05) in the 11-point box test, without worsening of spasticity, motor function or activities of daily living.

n=11 patients with chronic upper motor neuron syndrome and spasticity-related pain (13 included, 11 completed), nabilone 1 mg/day vs. placebo; significant pain reduction in the 11-point box test with nabilone (p<0.05), no change in spasticity, motor function or ADL. 5 patients reported side effects (moderate transient weakness, mild drowsiness, mild dysphagia); 2 drop-outs (1 weakness, 1 acute MS relapse).

Nabilone led to a significant reduction in spasticity in the most affected muscle group (Ashworth scale, P=.003) and in the total Ashworth score (P=.001), with no significant differences in other measures.

n=11 patients with spinal cord injury and spasticity; double-blind, placebo-controlled crossover pilot RCT with nabilone (0,5–1 mg/day) vs. placebo over 4 weeks each. Significant reduction in Ashworth score in the most affected muscle (mean difference 0,909 ± 0,85; p=0,003) as well as in the total Ashworth score (p=0,001). Adverse effects mild and tolerable.

Sativex showed significant superiority over placebo in maintaining efficacy against spasticity in MS patients (primary endpoint: time to treatment failure p=0,013; secondary endpoints also significant in favor of Sativex).

Nabiximols (Sativex) vs. placebo; n=36 (18/group each); enriched-enrollment randomised withdrawal study over 5 weeks in MS patients with demonstrated long-term efficacy (≥12 weeks); primary endpoint time to treatment failure significant in favor of nabiximols (p=0,013); Global Impression of Change (patient + carer) also significantly improved.

THC significantly reduced the spasticity sum score compared to baseline and placebo (p=0,001).

n=25 patients with spinal cord injury; oral THC (mean daily dose 31 mg) significantly decreased the spasticity sum score (SSS, Modified Ashworth Scale) from 16,72 to 8,92 (p=0,001); rectal THC-HS showed similar effect.

Nabiximols showed no significant benefit over placebo on the primary endpoint (MAS LLMT-6 change): treatment difference 0,04 (P=0,7152).

n=68 MS patients with spasticity; nabiximols (THC:CBD oral spray) vs. placebo, phase III crossover RCT (RELEASE MSS1); primary endpoint MAS LLMT-6 not met (LS-mean difference 0,04; p=0,72). The objective clinical muscle tone endpoint did not differ significantly between groups despite established efficacy on patient-reported NRS spasticity scores in earlier studies.

CBD-rich cannabis oil significantly improved spasticity, dystonia, sleep, pain and quality of life in children with complex movement disorders.

n=25 children (1–17 y.) with complex movement disorder (spasticity + dystonia), CBD-enriched cannabis oil (20:1 vs. 6:1 THC group), 5 months; significant improvement in spasticity and dystonia as well as sleep problems and pain intensity in the overall cohort; adverse events rare: seizure worsening in 2 patients, behavioral change in 2, somnolence in 1.

Sativex showed a known, well-tolerated safety profile in the long-term registry with no new safety signals; 83% of patients reported a clinical benefit.

n=941 MS spasticity patients, 2.213,98 patient-years with Sativex® (THC:CBD). 83% reported benefit for treatment-resistant spasticity; 60% continued treatment. Most common ADRs: dizziness 2,3%, fatigue 1,7%. No signal for dependence or abuse. Driving ability improved in 7%, worsened in 2%. Long-term risk profile consistent with the known safety profile — no new safety concerns.

Nabiximols reduced spasticity NRS in a clinically meaningful way and improved quality of life in the majority of treated MS patients.

n=238 MS spasticity patients (Belgium, 8 centres), Sativex® nabiximols after failure of previous anti-spasticity drugs. Spasticity NRS from 8,1 to 4,1 (week 12). 74 % achieved ≥30 % NRS improvement (clinically meaningful). Average dose 6 sprays/day. >60 % of those starting treatment continued after week 12.

After one month, 70,5% of patients achieved a ≥20% improvement in spasticity; 28,2% achieved a clinically relevant ≥30% improvement with a mean NRS reduction of 22,6%.

n=1.615 MS patients with treatment-resistant spasticity, mandatory AIFA registry (Italy); THC:CBD oromucosal spray (Sativex). After 1 month: 70,5% achieved ≥20% NRS improvement (Initial Response), 28,2% ≥30% improvement (clinically relevant response); mean NRS reduction 22,6% (from 7,5 to 5,8). Increased probability of response with progressive MS (OR=1,4; 95%-CI 1,04–1,9; p=0,025) and NRS >8 at baseline (OR=1,8; 95%-CI 1,3–2,4; p<0,001). Discontinuation rate after 6 months: 39,5% (26,2% due to lack of efficacy, 18,7% due to adverse events).

About 60% of patients continued Sativex after 6 weeks, while a poorer early response and low baseline value were predictors of discontinuation.

Large real-world registry (n=1597 MS spasticity patients, 30 centres) on Sativex persistence; 39,5% discontinuation; Cox model: higher NRS week-4 score = 2,23-fold discontinuation risk (95%-CI 2,07–2,41, p<0,001); lower baseline NRS protective (adjHR=0,51, p<0,001); benefit identification possible within 6 weeks.

61,9% of patients achieved sufficient improvement in spasticity (≥20% NRS) after 1 month, 40,2% showed a clinically meaningful ≥30% NRS improvement after 6 months.

Prospective real-world registry study (AIFA, Italy) on THC:CBD oromucosal spray in MS spasticity; n=1.534 patients from 30 MS centres. After 1 month 61,9% achieved a ≥20% NRS improvement (continuation-of-treatment threshold); after 6 months 40,2% showed a clinically meaningful ≥30% NRS reduction. Mean daily dose 6,2–6,7 sprays; adverse events (predominantly mild to moderate) in 15% of patients, no new safety signals.

THC:CBD spray significantly improved MS-related spasticity and associated symptoms after 3 months with good tolerability.

Multicentre prospective observational study (MOVE-2 EU) on THC:CBD spray in treatment-resistant MS spasticity, n=433 (98% Italy). After 1 month 80.6% responders (≥20% spasticity improvement), after 3 months n=281 continuously treated. Mean dose 6 sprays/day. Significant improvement in spasticity scores, spasms, fatigue, pain, sleep quality, bladder function as well as quality of life (EQ-5D VAS). Adverse events in 10.4%, no serious events.

THC/CBD spray significantly reduced MS spasticity: NRS score decreased by 19,1% (p<0,0001), modified Ashworth score from 2,6 to 2,3 points (p<0,0001), 24,6% of patients showed ≥30% improvement.

Prospective observational study (MOVE 2 Italy interim analysis) on THC:CBD spray in treatment-resistant MS spasticity, n=322. From baseline to Month 3: mean NRS reduction -19,1% (-1,6 points, p<0,0001), modified Ashworth score 2,6→2,3 points (p<0,0001). 24,6% of patients clinically relevant responders (≥30% NRS improvement, p<0,001). Mean dose 5,1±2,6 sprays/day (Month 3). 13,1% reported AEs (most common: dizziness 5,6%, confusion 2,5%).

THC:CBD spray led to meaningful improvements in spasticity as measured by patient rating scale and modified Ashworth scale at lower doses and with fewer adverse events than in RCT.

Prospective observational study MOVE 2-Italy, n>300 MS patients with treatment-resistant spasticity, THC:CBD spray as add-on to baclofen over 3 months; significant improvement on 0-10 NRS and modified Ashworth scale at mean daily doses ~1/3 lower than in RCTs; discontinuation rate low, adverse event rate ~1/3 of RCT rate.

After 1 month 74,6% of patients reported relief of spasticity; the NRS score decreased on average by 25% after 3 months; 17% reported side effects.

MOVE 2 study: n=276, prospective non-interventional study (Germany); nabiximols spray as add-on for moderate to severe MS spasticity. NRS score decreased from 6,1 to 5,2 after 1 month; in ≥20% responders mean NRS reduction 40%. After 3 months 55,3% continued therapy; mean NRS reduction >25% versus baseline. 17% of patients reported side effects.

Nabiximols significantly and durably reduced spasticity and pain in MS patients for up to 48 weeks.

Real-world study (n=144 MS patients) on nabiximols (Sativex) for moderate to severe MS spasticity (sNRS 7,5); 71,7% responders, mean sNRS reduction 32% (p<0,001), improvement in Modified Ashworth Scale and walking test significant (p<0,05); effect stable up to 48 weeks.

Significant reduction in spasticity (NRS score by 2,5 ± 1,2 points, P < 0,0001) as well as improvement in pain and bladder function.

40-week real-world data on THC/CBD spray in n=102 MS patients with spasticity; average 6.5±1.6 sprays/day. Mean NRS spasticity reduction 2.5±1.2 points (p<0.0001). Responder criterion (≥20% NRS reduction after 4 weeks) as continuation criterion; 36.2% treatment discontinuation. Adverse event rate 40.2%. Additional significant improvements in pain (NRS, n=58, p=0.011) and bladder dysfunction (IPSS, n=46, p=0.001).

Significant reduction in stretch reflex amplitude as well as significant improvements in NRS and MAS scores under THC:CBD spray treatment for MS spasticity.

n=57 MS patients with spasticity, THC:CBD oromucosal spray before/during treatment; significant reduction in stretch reflex amplitude as well as significant improvements in NRS (Numeric Rating Scale) and MAS (Modified Ashworth Scale). Stretch reflex responders required significantly higher puff numbers. Low concordance between the three measures (stretch reflex, NRS, MAS), indicating different aspects of muscle hypertonia.

Significant reduction in spasticity (NRS from 6,0 to 4,5 points after 12 months), good tolerability (84% without side effects).

12-month extension of the MOVE 2 observational study on nabiximols in resistant MS spasticity, n=52 (Germany). Mean spasticity NRS score reduced from 6,0±1,8 (baseline) to 4,8±1,9 (month 1) and remained stable after 12 months (4,5±2,0 points). In initial responders (≥20% NRS improvement after 1 month): 6,3±1,4→4,0±1,0→4,3±1,9 points. 84% of patients reported no side effects. Confirms long-term efficacy and tolerability.

Nabiximols showed clinically meaningful improvements in MS-related spasticity with a 46% increase in Goal Attainment Scale, 23% improvement in walking speed, and clinically relevant improvements in spasticity, pain, sleep quality and bladder dysfunction.

n=51 MS patients with spasticity (49 responders), add-on nabiximols (Sativex) oromucosal spray, 12 weeks prospective multicenter real-world setting (Germany). Primary endpoint Goal Attainment Scale (GAS) increased by 46% (35,2 → 51,4; p<0,001). Walking speed improved by 23% after 4 and 12 weeks. Clinically meaningful improvements in NRS scores for spasticity, pain, sleep quality and bladder function.

Nabiximols measurably reduced MS-related spasticity (NRS from 7,6 to 5,5), and physiotherapy improved clinically relevant response rate and treatment persistence.

Observational multicenter cohort study (n=290, MS spasticity, real-world), nabiximols (THC:CBD spray) as add-on over 12 weeks. NRS spasticity score decreased from 7,6 to 5,5; 77% achieved ≥20% improvement (initial response), 22% ≥30% (clinically relevant response). Concomitant physiotherapy increased the clinically relevant response rate (OR=2,6; 95% CI 1,3–5,6; p=0,01) and decreased the discontinuation rate after 12 weeks (HR=0,41; 95% CI 0,23–0,69; p=0,001).

Most respondents reported subjective symptom relief from cannabis, most frequently for spasticity and chronic pain.

n=112 MS patients (53 UK + 59 USA), anonymous questionnaire. Spasticity was the most frequently improved symptom: 97% reported improvement from smoking cannabis. Results motivated initial clinical trial planning on cannabis for MS spasticity.

THC/CBD was effective in 80% of patients for improving spasticity in multiple sclerosis.

Retrospective study n=50 MS patients with inhaled THC/CBD (April 2008–March 2012). Indication: spasticity (44%), pain (10%), both (46%). THC/CBD effective in 80% of patients, median dose 5 (2-10) inhalations/day. Median exposure interval 174 days with continuation vs. 30 days with discontinuation (n=16 due to ineffectiveness, withdrawal, side effects). Side effects: dizziness (n=11), somnolence (6), muscle weakness (7), others mild.

Sativex does not negatively affect fitness to drive and statistically significantly improves self-reported spasticity severity.

n=33 MS patients with treatment-resistant spasticity, 4-6 weeks Sativex add-on therapy. Fitness-to-drive tests (validated computer-based test battery) showed no deterioration under treatment; only 2 patients changed classification (1 to 'fit', 1 to 'unfit'). Mean spasticity severity (self-report) improved statistically significantly (p<0.05). Sativex well tolerated.

Pain, spasticity and sleep disturbances decreased significantly; no impairment in degree of disability, ambulation, dexterity or processing speed.

Prospective safety study in n=28 MS patients, sublingual cannabis oils (THC-rich/CBD-rich/combined) over 4-week titration, mean doses THC 4,0 mg/CBD 7,0 mg daily; spasticity NRS reduction from median 6 to 2,5 (p=0,01), pain NRS from 7 to 4 (p=0,01), sleep disturbances NRS from 7 to 3 (p<0,001); most common side effects: dry mouth, drowsiness, dizziness, nausea (mild-moderate); 2 treatment discontinuations due to pronounced symptoms.

Significant improvements in processing speed and auditory-verbal memory performance within the first 6 months; spasticity improved significantly; mood and anxiety showed no significant changes.

Prospective pilot study on long-term cognitive effects of nabiximols (THC/CBD spray) in n=20 MS patients with spasticity over 12 months. Significant improvements in processing speed (SDMT: p<0,001) and auditory verbal memory (CVLT: p=0,0001) after 6 months. NRS spasticity score significantly improved from baseline (p<0,0001). Mood and anxiety without significant change.

Dronabinol reduced or eliminated refractory spasticity in 12 of 16 pediatric palliative patients.

Retrospective open study, n=16 pediatric palliative patients with refractory spasticity (age 1,3–26,6 years); dronabinol 0,08–1,0 mg/kg/d (median 0,33 mg/kg/d); 12/16 patients with marked improvement or resolution of spasticity; mean treatment duration 181 days (range 23–1429 days); adverse effects: only vomiting and agitation each in 1 patient.

Nabiximols showed good tolerability and a safe profile in the treatment of spasticity and chronic pain in everyday clinical practice, with frequent but expected side effects (dizziness, fatigue, somnolence) and a low rate of serious adverse events (3,1% in MS spasticity studies).

Systematic review of k=24 observational studies, registry analyses and case reports on nabiximols (THC:CBD spray) in MS spasticity (n=4.351); consistent side effects were dizziness, fatigue and somnolence. SAE rate 3,1% (137/4.351), 39 treatment-related SAEs in 32 patients, all (where specified) resolved. Real-world experience shows good tolerability and safety profile.

Cannabinoids show probable efficacy for MS-associated spasticity and pain, but are associated with relevant safety risks.

Narrative review on cannabinoids in MS spasticity; Nabiximols, oral cannabis extract and synthetic THC 'probably effective' for reducing patient-reported spasticity symptoms in MS (20–40 mg THC/day); no significant effect on physician-assessed spasticity measures (no effect on Ashworth scale). Adverse effects more frequent in cannabinoid groups, but serious events rare.