What multiple sclerosis spasticity is
Multiple sclerosis (MS) is a chronic condition in which the immune system attacks the protective myelin sheath around nerve fibres in the brain and spinal cord. This damage disrupts the normal transmission of nerve signals, producing a range of neurological symptoms. Spasticity is one of the most common and disabling symptoms of MS, estimated to affect between 60 and 84 per cent of people with the condition.
Spasticity in MS arises from damage to the upper motor neuron pathways that regulate muscle stretch reflexes. It produces increased muscle tone that is velocity-dependent — the faster a muscle is stretched, the stronger the resistance. This leads to stiffness, painful involuntary muscle spasms, difficulty with movement and positioning, and disrupted sleep. When spasticity does not respond adequately to first-line oral treatments such as baclofen, gabapentin, or tizanidine, it is described as treatment-resistant or refractory.
Cannabis research on Multiple sclerosis spasticity
Nabiximols (brand name Sativex) is an oromucosal spray containing THC and CBD in an approximately 1-to-1 ratio. It is licensed by the Medicines and Healthcare products Regulatory Agency (MHRA) as an add-on treatment for moderate to severe spasticity in MS when other anti-spasticity medicines have not provided adequate relief.
A key double-blind, placebo-controlled, randomised trial by Novotna and colleagues, published in 2011, used an enriched design. In the first phase, 572 people with MS and treatment-resistant spasticity received nabiximols in a four-week single-blind period. The 272 participants who achieved at least a 20 per cent improvement in their spasticity numerical rating scale (NRS) score were then randomised to continue nabiximols or switch to placebo for 12 weeks. The primary endpoint, the change in spasticity NRS score, showed a statistically significant difference in favour of nabiximols (p=0.0002). This finding came from an intention-to-treat analysis. Secondary endpoints including spasm frequency, sleep disturbance, and the clinical global impression of change — assessed by the patient, carer, and clinician — were also significantly better in the nabiximols group.
The enriched design is a deliberately structured clinical trial method. The randomised phase only included people who had already shown a response, which means the results apply to people who demonstrate an initial benefit rather than to everyone with MS spasticity.
The 2015 systematic review and meta-analysis by Whiting and colleagues rated the quality of evidence for cannabinoids in MS spasticity as moderate. The review included trials of both nabiximols and oral cannabinoid preparations.
An animal study by Mecha and colleagues, published in 2013, examined CBD in a viral mouse model of MS. The study found that CBD provided protection against the inflammatory effects of the disease, an outcome the authors linked to adenosine A2A receptor activation. This is an animal model finding and does not establish the same effect in people with MS.
Compounds studied for Multiple sclerosis spasticity
THC has been studied in human RCTs as a component of nabiximols for MS spasticity. The CB1 receptors activated by THC are present in motor control pathways in the brain and spinal cord. The clinical trial evidence for THC in spasticity comes from the specific nabiximols formulation, not from isolated THC or cannabis flower. See THC.
CBD has been examined in an animal model of MS, where it reduced markers of inflammation and demyelination. This is laboratory and animal research. No human RCT has tested isolated CBD for MS spasticity as a primary outcome. See CBD.
CBG has been studied in cell and animal research for neuroprotective and anti-inflammatory properties. Human clinical trial data for CBG in MS or spasticity are absent. See CBG.
THCA has been noted in laboratory research for anti-inflammatory and neuroprotective properties. No human RCT has tested THCA for MS or spasticity outcomes. See THCA.
Caryophyllene binds to the CB2 receptor, which is expressed on immune cells involved in neuroinflammatory processes. Cell and animal research has examined caryophyllene for anti-inflammatory effects in models relevant to neuroinflammation. Human trial data for caryophyllene in MS are absent. See beta-caryophyllene.
Myrcene has been studied in rodent models for muscle-relaxant effects. It has not been tested in human RCTs for spasticity. See myrcene.
Limonene has been examined in laboratory and animal studies for anti-inflammatory properties. No human clinical trial has tested isolated limonene for MS or spasticity. See limonene.
Limits of the evidence for Multiple sclerosis spasticity
The main RCT evidence comes from an enriched-design study, which means the randomised comparison was restricted to people who had already shown a response to the treatment during an initial open-label phase. The absolute treatment effect in people with MS spasticity who have not been pre-selected for response is less certain.
The licensed product is a specific pharmaceutical formulation with a defined ratio of THC to CBD and a standardised oromucosal delivery method. Trial results for nabiximols do not provide evidence that smoked cannabis, vaporised cannabis, or non-standardised cannabis preparations produce the same effects on spasticity.
The controlled trial data cover periods of weeks to months. While observational studies report sustained effects over longer periods, these do not include a placebo comparison and cannot exclude confounding.
In the enriched trial, roughly half of the initial participants did not show a sufficient response in the single-blind phase to enter the randomised phase. This means that about half of people with MS spasticity who try this treatment may not achieve a clinically meaningful response within the initial assessment period.
Sources
1. Novotna A, Mares J, Ratcliffe S, et al. A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols (Sativex), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur J Neurol. 2011;18(9):1122-1131. doi:10.1111/j.1468-1331.2010.03328.x. PMID: 21362108. Study record
2. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015;313(24):2456-2473. doi:10.1001/jama.2015.6358. PMID: 26103030. Study record
3. Mecha M, Feliu A, Inigo PM, Mestre L, Carrillo-Salinas FJ, Guaza C. Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: a role for A2A receptors. Neurobiol Dis. 2013;59:141-150. doi:10.1016/j.nbd.2013.06.016. PMID: 23851394. Study record
