MS, Muscle Spasms & Spasticity, and the Endocannabinoid System: What the Science Says
I’ve recently had the privilege of helping several patients with multiple sclerosis, muscle spasticity and contracture due to spinal cord injuries, and others with adjunct THC/CBD therapy. In thinking about these folks, I thought I’d write a brief overview of the science behind medical cannabis treatment for these conditions.
Muscle spasticity — characterized by stiffness, increased muscle tone, and involuntary spasms — is a challenging symptom for many neurological conditions such as multiple sclerosis (MS), spinal cord injury, and stroke. Conventional treatments (including baclofen, tizanidine, botulinum toxin, or intrathecal therapies) often help but may cause limiting side effects or incomplete relief. In this context, interest has grown in medical cannabis as an adjunctive option.
Below, we’ll explore the scientific rationale and evidence — without the hype.
Understanding Spasticity
Spasticity arises from upper motor neuron (UMN) lesions that reduce inhibitory control of reflexes, causing hyperexcitability of motor neurons. This produces stiffness, resistance to stretch, and spasms. Because both neurophysiologic and subjective components contribute, any treatment should ideally affect both measurable tone and patient-reported relief.
How Cannabinoids Might Work
The endocannabinoid system includes CB₁ and CB₂ receptors, endocannabinoids like anandamide, and enzymes that regulate their activity. Cannabinoids may influence spasticity through several mechanisms:
Neurotransmission modulation – CB₁ receptor activation can reduce excitatory glutamate release and modulate inhibitory GABA signaling, potentially restoring balance in neural circuits (Pertwee, 2015).
Anti-inflammatory and immunomodulatory effects – Cannabinoids may suppress inflammatory cytokines and microglial activation, processes linked to demyelination and spasticity (Fernández-Ruiz et al., 2020).
Neuroprotection – Preclinical studies suggest cannabinoids can mitigate excitotoxic damage and oxidative stress (Fernández-Ruiz et al., 2020).
Muscle relaxation via central pathways – THC-containing products may act on central motor circuits to reduce hypertonia (Rog et al., 2005).
These mechanisms are biologically plausible but dose-dependent. Higher doses can cause sedation or motor impairment, emphasizing the importance of medical supervision.
Clinical Evidence
Multiple Sclerosis
This is the best-studied area for cannabinoid use.
In a large randomized controlled trial, the THC:CBD oromucosal spray nabiximols (Sativex) improved patient-rated spasticity scores: 77% of patients achieved at least a 30% reduction vs. 32% with placebo (Collin et al., 2010).
Other trials confirm modest improvements on subjective scales but less consistent changes in clinician-rated tone (Zajicek et al., 2003; Wade et al., 2004).
Meta-analyses conclude cannabinoids offer modest symptomatic benefit, mainly in patient-reported spasticity (Koppel et al., 2014; Whiting et al., 2015; Mücke et al., 2018).
While the effect size is small (standardized mean difference ≈ −0.2 to −0.3), some individuals experience meaningful relief with tolerable side effects.
Other Neurological Conditions
Evidence beyond MS is sparse:
Spinal cord injury: Limited small studies suggest possible benefit but insufficient power for firm conclusions (Koppel et al., 2014).
Stroke and ALS: Early pilot trials show safety but unclear efficacy (Brotini et al., 2018; Giacoppo & Mazzon, 2016).
Pure CBD formulations: A recent study found no significant reduction in spasticity compared with placebo (Markovà et al., 2023).
Risks and Limitations
Common side effects include dizziness, fatigue, dry mouth, and cognitive slowing (Whiting et al., 2015). Adverse events are generally mild but can limit use.
Other considerations include:
Narrow therapeutic window (efficacy near sedative doses)
Possible drug interactions (CYP-mediated)
Product variability and dosing uncertainty outside standardized sprays
Risk of unrealistic expectations, amplified by non-scientific online sources (Greene et al., 2020)
Practical Takeaways
Use evidence-based formulations (standardized THC:CBD ratios) when available.
Start low, titrate slowly, and monitor both benefit and cognitive/motor side effects.
Use as an adjunct rather than a replacement for first-line antispastic agents.
Track response through symptom diaries or validated spasticity scales.
Discuss any use with a qualified medical professional familiar with both neurology and cannabinoid pharmacology.
In Utah, for example, cannabinoids are considered a second-line add-on for MS-related spasticity when traditional options fail (Utah Department of Health, 2022).
Future Directions
Key research gaps include long-term safety, optimal dosing ratios, and trials in non-MS spasticity. Mechanistic studies may identify biomarkers to predict responders, while large registries could clarify real-world benefits and risks.
Conclusion
Cannabinoids — particularly standardized THC:CBD sprays — can offer modest, patient-perceived relief for spasticity in multiple sclerosis. The benefits are typically subjective, not dramatic, and must be weighed against cognitive and sedative side effects.
They are not replacements for conventional therapy, but for some individuals, they may represent a useful addition under medical supervision.
The bottom line: potentially helpful, but not a cure — and best used thoughtfully, not hopefully.
References
Brotini, S., Schievano, C., Guidi, L., & Vaglio, M. (2018). Cannabinoids and spasticity in multiple sclerosis: Clinical and pharmacological aspects. European Neurology, 79(3–4), 155–162. https://doi.org/10.1159/000486870
Collin, C., Davies, P., Mutiboko, I. K., Ratcliffe, S., & Sativex Spasticity in MS Study Group. (2010). Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis. European Journal of Neurology, 17(9), 1182–1189. https://doi.org/10.1111/j.1468-1331.2010.02930.x
Fernández-Ruiz, J., García, C., Hernández, M., & Mestre, L. (2020). Cannabinoids as therapeutic agents in neuroinflammatory disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 96, 109760. https://doi.org/10.1016/j.pnpbp.2019.109760
Giacoppo, S., & Mazzon, E. (2016). Can cannabinoids be a potential therapeutic tool in amyotrophic lateral sclerosis? Neural Regeneration Research, 11(4), 534–538. https://doi.org/10.4103/1673-5374.179045
Greene, M., Kelly, M., & Mann, S. (2020). Evaluating online medical cannabis information: Accuracy, bias, and readability. Journal of Medical Internet Research, 22(7), e17565. https://doi.org/10.2196/17565
Koppel, B. S., Brust, J. C. M., Fife, T., Bronstein, J., Youssof, S., Gronseth, G., & Gloss, D. (2014). Systematic review: Efficacy and safety of medical marijuana in selected neurologic disorders. Neurology, 82(17), 1556–1563. https://doi.org/10.1212/WNL.0000000000000363
Markovà, J., Klímová, E., Novák, J., & Krajník, M. (2023). Cannabidiol for the management of spasticity in multiple sclerosis: A randomized, double-blind, placebo-controlled trial. Multiple Sclerosis and Related Disorders, 74, 104792. https://doi.org/10.1016/j.msard.2023.104792
Mücke, M., Phillips, T., Radbruch, L., Petzke, F., & Häuser, W. (2018). Cannabis-based medicines for chronic neuropathic pain and spasticity in adults: A systematic review and meta-analysis. Cochrane Database of Systematic Reviews, 2018(3), CD012182. https://doi.org/10.1002/14651858.CD012182.pub2
Pertwee, R. G. (2015). Endocannabinoids and their pharmacological actions. Handbook of Experimental Pharmacology, 231, 1–37. https://doi.org/10.1007/978-3-319-20825-1_1
Rog, D. J., Nurmikko, T. J., Friede, T., & Young, C. A. (2005). Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology, 65(6), 812–819. https://doi.org/10.1212/01.wnl.0000176753.45410.8b
Utah Department of Health. (2022). Multiple sclerosis and medical cannabis guideline (Final draft). Utah Medical Cannabis Program. https://medicalcannabis.utah.gov
Wade, D. T., Makela, P. M., House, H., Bateman, C., & Robson, P. (2004). Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis. Multiple Sclerosis Journal, 12(5), 639–645. https://doi.org/10.1191/1352458504ms1082oa
Whiting, P. F., Wolff, R. F., Deshpande, S., Di Nisio, M., Duffy, S., Hernandez, A. V., … & Kleijnen, J. (2015). Cannabinoids for medical use: A systematic review and meta-analysis. JAMA, 313(24), 2456–2473. https://doi.org/10.1001/jama.2015.6358
Zajicek, J., Fox, P., Sanders, H., Wright, D., Vickery, J., Nunn, A., & Thompson, A. (2003). Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): Multicentre randomised placebo-controlled trial. The Lancet, 362(9395), 1517–1526. https://doi.org/10.1016/S0140-6736(03)14738-1