Assessing the Role of Cannabis in Managing Spasticity in Multiple Sclerosis: A Systematic Review and Meta-Analysis

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“Background: Multiple sclerosis (MS) is a complex, heterogeneous disease, and its management remains challenging due to varying symptoms and patient responses to treatments. While injectable therapies like glatiramer acetate and beta-interferon are common, they have limitations such as side effects and varying efficacy. Cannabis has garnered attention as a potential alternative treatment, particularly for symptoms like spasticity and pain.

Objective: This study aims to evaluate the efficacy of cannabis-based therapies for managing MS-related spasticity.

Methods: Nine clinical trials involving 2544 MS patients were included, with studies conducted between 2003 and 2021 across multiple countries. Cannabinoid therapies studied included whole-plant extracts, oils, and smoked cannabis containing delta-9-tetrahydrocannabinol and/or cannabidiol. Spasticity was assessed using standardized scales, including the Ashworth scale (AS), visual analog scale, and numeric rating scale (NRS). Effect sizes were pooled using random or fixed effects models, and heterogeneity and publication bias were evaluated using I², Tau², and funnel plots.

Results: The overall meta-analysis revealed a standardized mean difference (MD) of 39.19 (95% CI: 34.32-44.05) in spasticity scores, indicating notable improvement post-treatment. Subgroup analyses showed a MD of 20.36 (95% CI: 20.35-20.37) for AS and 1.18 (95% CI: 1.16-1.21) for NRS. However, substantial heterogeneity (I² = 100% for overall and AS analyses; 91% for NRS) and asymmetry in funnel plots suggest possible publication bias and study variability. Short-term studies demonstrated modest changes (MD = 4.53, 95% CI: -0.06 to 9.12), while long-term studies yielded larger effects (MD = 75.81, 95% CI: 66.39-85.22). Adverse events were generally mild, including dizziness and dry mouth.

Conclusion: Cannabis-based therapies are associated with clinically meaningful improvements in MS-related spasticity, particularly over longer durations. Despite the promising findings, high heterogeneity and suspected bias necessitate caution. Further high-quality randomized trials with standardized protocols and comprehensive safety assessments are warranted to validate efficacy and long-term outcomes.”

https://pubmed.ncbi.nlm.nih.gov/40753057/

Pilot Study of Cannabidiol for Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in Breast Cancer

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“Introduction: Aromatase inhibitor (AI) therapy reduces breast cancer recurrence risk. However, some patients stop treatment early because of AI-associated musculoskeletal symptoms (AIMSS). AIMSS is due in part to systemic inflammation. Cannabidiol (CBD) has anti-nociceptive and anti-inflammatory properties, making it a potential treatment option for AIMSS.

Methods: Women with stage 0-3 hormone receptor-positive breast cancer experiencing AIMSS enrolled in this phase 2 clinical trial. Patients received CBD (Epidiolex), titrated over 4 weeks to 100 mg BID, for a total of 15 weeks. Patient-reported outcomes were collected serially. The primary endpoint was the number of patients with at least a 2-point reduction in worst pain from baseline to 15 weeks. Statistical analysis was completed using paired t-tests and linear mixed models.

Results: Of 39 eligible patients, 28 completed protocol-directed study treatment. Eleven discontinued treatment due to toxicity (n = 5) or per patient preference (n = 6). Seventeen of 39 patients met the primary endpoint (43.6%, 95% CI [28%, 60%]). Worst pain improved 0.13 per week of treatment (p < 0.001) for all patients; average improvement in worst pain was 1.95 points at the end of 15 weeks. Of the 28 patients who completed the study, average reduction in worst pain was 2.36 points (95% CI [-3.22, -1.49]) between baseline and Week 15.

Conclusion: Treatment with CBD was safe, tolerable, and associated with improvement in joint pain for a subset of patients. Additional studies are needed to further understand the impact of CBD on AIMSS and which patients are most likely to benefit from CBD treatment.”

https://pubmed.ncbi.nlm.nih.gov/40751295/

“Treatment with CBD was associated with an improvement in AIMSS for a subset of patients. Use of CBD was safe and tolerable for women with hormone receptor-positive breast cancer.”

https://onlinelibrary.wiley.com/doi/10.1002/cam4.71117

Efficacy and safety of cannabidiol in a single-center pediatric drug-resistant epilepsy cohort: a retrospective study

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“Background: Pharmacoresistance to conventional antiseizure medications has been described in approximately 30% of the pediatric epileptic patients, making pharmacological management particularly challenging for physicians. Currently, cannabidiol (CBD) is approved as an adjunctive therapy in combination with clobazam for Dravet Syndrome (DS), Lennox-Gastaut Syndrome (LGS), and as adjunctive treatment for Tuberous Sclerosis Complex (TSC). Studies on drug-resistant epilepsy (DRE) suggested that CBD antiepileptic properties may benefit a wider range of pharmacoresistant epilepsy syndromes.

Objective: Our observational, retrospective, monocentric study aimed to evaluate the effect and safety of CBD in a real-world pediatric cohort with DRE.

Methods: We recruited 15 pediatric patients (7 females, 8 males; mean age: 12.33 ± 4.37 years) affected by pharmacoresistant epilepsy treated with CBD as adjunctive therapy. Inclusion criteria required a diagnosis of DRE, initiation of CBD treatment before 18 years of age, and at least 6 months period of follow-up after CBD initiation. Clinical, demographic, and instrumental data were retrospectively extracted from the medical records and caregivers’ reports. Based on seizure reduction, patients were stratified into “responders” (>50%), “partial responders” (30-50%), and “non-responders” (<30%) groups.

Results: CBD was used as an add-on therapy in 8/15 patients on-label (for DS, LGS, and TSC) and in 7/15 off-label. The maximum dose of CBD administered was 21 mg/kg/day, with an average dose of 16.5 mg/kg/day. 11/15 patients showed a reduction in seizure frequency: 7 were responders (2/7 seizure-free) and 5 were partial responders. Additionally, 11/15 patients showed improved social and environmental participation, as assessed using the Clinical Global Impression scale. Interestingly, brain magnetic resonance imaging revealed structural abnormalities in 5/15 patients, with 6/15 showing malformations of cortical development (4/6 responders, including 1 seizure-free).

Conclusion: CBD demonstrated a good safety and tolerability profile and appeared to be a promising therapeutic option for the management of DRE. It offers a valuable alternative for seizure control and has a positive impact on social interaction, with overall improvement in the quality of life for patients and their caregivers.”

https://pubmed.ncbi.nlm.nih.gov/40740850/

“In conclusion, CBD may represent a promising therapeutic option capable of enhancing the clinical management of DRE. Indeed, it offers a valuable alternative for seizure treatment and positively impacts social interaction and quality of life for the patients and their caregivers.”

https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1616480/full

Expanding the Therapeutic Profile of Topical Cannabidiol in Temporomandibular Disorders: Effects on Sleep Quality and Migraine Disability in Patients with Bruxism-Associated Muscle Pain

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“Background: Cannabidiol (CBD) has demonstrated potential as a therapeutic agent for muscle tension, pain, and sleep bruxism, yet its broader impact on comorbid conditions such as sleep disturbance and migraine disability remains underexplored. This study aimed to assess the effects of topical CBD on sleep quality and migraine-related disability in patients with bruxism-associated muscular pain. 

Methods: In a randomized, double-blind clinical trial, 60 participants with bruxism were allocated equally into three groups: control (placebo gel), 5% CBD gel, and 10% CBD gel. Participants applied the gel intraorally to the masseter muscles nightly for 30 days. Sleep quality and migraine-related disability were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Migraine Disability Assessment Scale (MIDAS), respectively. Surface electromyography (sEMG) and the Bruxoff® device were used for objective evaluation of muscle tension and bruxism intensity. 

Results: Both CBD treatment groups demonstrated statistically significant improvements in PSQI and MIDAS scores compared to the control group (p < 0.001). No significant differences were observed between the 5% and 10% CBD groups, suggesting comparable efficacy. The sEMG findings corroborated a reduction in muscle tension. Improvements in sleep and migraine outcomes were positively correlated with reductions in muscle activity and pain. 

Conclusions: Topical CBD gel significantly improved sleep quality and reduced migraine-related disability in patients with bruxism-associated muscular pain, supporting its role as a multifaceted therapeutic option in the management of TMD and related comorbidities. Further research is needed to confirm long-term benefits and determine optimal dosing strategies.”

https://pubmed.ncbi.nlm.nih.gov/40732351/

“This study demonstrates that topical application of cannabidiol (CBD) gel, at both 5% and 10% concentrations, significantly improves sleep quality and reduces migraine-related disability in patients with bruxism-associated muscular pain. These effects were observed alongside reductions in muscle tension and pain, suggesting a broader therapeutic impact of CBD beyond localized symptom relief. Notably, no substantial differences were found between the two concentrations, indicating that lower doses may achieve comparable clinical outcomes.

The findings support the use of topical CBD as a well-tolerated, non-invasive adjunct in the multimodal management of temporomandibular disorders (TMD), especially in patients experiencing comorbid sleep and headache disturbances. Future research should explore long-term efficacy, optimal dosing, and underlying mechanisms through objective neurophysiological and sleep assessments”

https://www.mdpi.com/1424-8247/18/7/1064