Introduction 

Multiple sclerosis (MS) is a chronic, immune-mediated disease characterised by inflammation and demyelination of the central nervous system (CNS). This degenerative disease impairs nerve signal transmission, resulting in a variety of emotional, mental, and physical difficulties.¹ Amongst the many symptoms of multiple sclerosis, up to 80% of people have spasticity, a disorder characterised by stiffness and involuntary muscle spasms that severely reduce mobility, everyday functioning, and overall quality of life.¹ In addition to complicating illness management, spasticity can present in a range of severities, from minor pain to debilitating immobility.¹

Traditional pharmaceutical therapies for spasticity include diazepam, tizanidine, and baclofen, which relax muscles. Although some patients may find relief from these drugs, their effectiveness is frequently limited, and they are linked to serious adverse effects such as drowsiness, muscle weakness, and the possibility of dependency.² Alternative treatment approaches that provide efficient symptom management with fewer side effects are therefore becoming increasingly necessary.

In recent years, cannabis and its derivatives have shown promise as treatments for spasticity associated with multiple sclerosis. Tetrahydrocannabinol (THC) and cannabidiol (CBD), two active substances found in cannabis, interact with the body's endocannabinoid system to exert therapeutic effects.³ This article examines the mechanisms by which cannabis can reduce spasticity, evaluates the clinical data supporting its use, and discusses the potential advantages and challenges associated with this approach.

Mechanisms of cannabis in spasticity management

The main way that cannabis works involves the endocannabinoid system, which is made up of endogenous cannabinoids (endocannabinoids), cannabinoid receptors (CB1 and CB2), and related enzymes.³ The mechanism is essential for controlling muscle contraction, inflammation, and pain.

Endocannabinoid modulation's function

CB1 and CB2 receptors are bound by naturally occurring lipid-based neurotransmitters called endocannabinoids, which include anandamide and 2-arachidonoylglycerol (2-AG).³ This system is dysregulated in MS, which leads to motor neuron hyperexcitability and spasticity. Exogenous cannabinoids, such as THC and CBD, balance the body by supplementing the endogenous cannabinoids, which decreases muscle stiffness and spasms.³

A decrease in the release of neurotransmitters

By activating the CB1 receptor, THC prevents excitatory neurotransmitters like glutamate and acetylcholine from being released at neuromuscular junctions. By reducing the reflex arcs linked to spasticity, this activity alleviates symptoms.⁴

The synergistic function of CBD

CBD works indirectly, for instance by raising anandamide levels by preventing its enzymatic degradation, but it has a lower affinity for CB1 and CB2 receptors than THC. CBD's ability to relax muscles and reduce pain is also attributed to its modulation of additional receptors, such as serotonin and vanilloid receptors.⁵

Reduced inflammatory effects 

When immune cells' CB2 receptors are activated, pro-inflammatory cytokines such as interleukins and tumour necrosis factor-alpha (TNF-α) are suppressed. This technique tackles the underlying cause of spasticity, as inflammation is the primary driver of demyelination and axonal damage in multiple sclerosis.⁶

Benefits of cannabis in spasticity management

Improved quality of life

Cannabis has shown potential in improving the general quality of life for MS patients by reducing spasticity and related symptoms like pain and sleep problems. Patients can carry out everyday tasks more easily when their muscle stiffness and spasms are relieved, which promotes independence and higher self-esteem.⁷ Furthermore, patients frequently report increased mobility and decreased reliance on carers, which can have a favourable effect on social connections and emotional health. Improved daytime performance and general vitality are further facilitated by better management of sleep difficulties, a typical complaint in multiple sclerosis. These advantages add up to enable a more comprehensive strategy for managing symptoms.⁷

Reduced polypharmacy

Cannabis may make it possible to lower the dosage or perhaps stop using other drugs that are typically used to treat spasticity, like opioids, muscle relaxants, or antispasmodics.⁸ The likelihood of adverse effects, such as drowsiness, cognitive decline, and gastrointestinal distress, which are frequently linked to traditional therapy, can be reduced by reducing polypharmacy. Additionally, fewer drugs mean fewer chances of drug-drug interactions, which makes treatment plans easier to follow and increases medication adherence.⁸ In addition to helping the patient, this simplified method lessens the financial strain of treating long-term illnesses.

Broad symptomatic relief

Cannabis treats a variety of additional MS-related symptoms in addition to spasticity, providing a more thorough therapeutic approach. It has been shown that cannabinoids can effectively relieve neuropathic pain, a crippling ailment that frequently defies conventional medications.⁹ Furthermore, some research indicates that cannabis may assist in treating bladder dysfunction by lessening incontinence and urgency, which would increase patient comfort and convenience.¹⁰ Cannabis use has also been shown to alleviate fatigue, one of the most prevalent and difficult symptoms of multiple sclerosis, enabling patients to participate more fully in day-to-day activities.⁹ Given the complexity and interconnectedness of MS symptoms, cannabis's diverse benefit profile highlights its value as a flexible and adaptable supplement to treatment plans.

Clinical evidence supporting cannabis for spasticity in MS

Several clinical studies and systematic reviews have investigated the efficacy of cannabis-based medicines in managing MS-related spasticity.

Randomised controlled trials (RCTs) with Sativex 

The study involved 337 participants over 15 weeks. The results showed that Sativex led to a greater reduction in spasticity symptoms compared to a placebo, particularly in those who followed the treatment protocol correctly (79% of subjects).¹¹ Specifically, Sativex reduced spasticity by 1.3 points on a 0-10 scale, compared to 0.8 points for the placebo. Additionally, 36% of participants using Sativex saw a 30% or more improvement in symptoms, compared to 24% in the placebo group.¹¹ The study concluded that Sativex is an effective treatment for MS-related spasticity, providing considerable relief for patients who did not respond well to conventional therapies.

Meta-Analyses and systematic reviews

According to a comprehensive meta-analysis conducted by the National Academies of Sciences, Engineering, and Medicine, there is robust evidence suggesting that cannabis can be beneficial in alleviating spasticity in patients with multiple sclerosis (MS), particularly when conventional treatments fail to provide adequate relief.¹² The analysis points to cannabis as a promising therapeutic option for managing symptoms of spasticity, a common and debilitating issue in MS.

Patient-Reported outcomes


High levels of satisfaction with cannabis-based treatments for spasticity are routinely reported by patients. A study found that a significant number of MS patients had used cannabis to manage their symptoms, with many reporting a positive impact on spasticity, pain, and overall quality of life.¹³ Over half of the participants noted significant relief from spasticity, with some even preferring cannabis to traditional pharmaceutical treatments due to fewer side effects and greater effectiveness.¹³ The study also highlighted that patients used cannabis in various forms, and the decision to use it was often driven by a lack of satisfactory results from conventional medications.¹³

Potential risks and challenges

• Adverse effects: THC-dominant cannabis frequently causes dry mouth, cognitive impairment, and dizziness as side effects. Dependence and, in certain situations, a worsening of mental symptoms have been linked to prolonged use³
• Response Variability & Genetic Variations: The course of the disease and previous exposure to cannabinoids all contribute to the wide range of responses that people have to cannabis. Standardising dosage and treatment is made more difficult by this diversity¹⁴
• Accessibility and Regulatory Concerns: Different jurisdictions have different legal statuses for medical cannabis, which makes it difficult for patients to get it. Financial hurdles may also arise since insurance may not cover the cost of cannabis-based drugs like Sativex³
• Limited Long-Term Data: Long-term evidence on cannabis's effects, especially on disease progression and cognitive outcomes, is still limited, despite short-term research demonstrating its safety and effectiveness in treating spasticity³

Future directions


Several topics require further research to maximise the potential of cannabis in managing MS-related spasticity. Advances in pharmacogenomics could enable the customisation of cannabis-based treatments tailored to individual patient profiles, optimising therapeutic benefits while minimising risks.¹² Developing standardised formulations and evidence-based dosing guidelines would enhance the consistency and reproducibility of cannabis treatments.¹² Additionally, exploring the synergy between cannabinoids and other pharmaceuticals could reveal novel combination therapies for spasticity management. Finally, large-scale, long-term randomised controlled trials (RCTs) are essential to confirm the safety and efficacy of cannabis for MS-related spasticity and to investigate its impact on other aspects of the condition.¹²

Summary

For MS patients with spasticity, cannabis holds promise, especially for those who have not responded to traditional treatments. Strong preclinical and clinical data support its effectiveness, and its several modes of action target the underlying causes of spasticity as well as its symptoms. But there are obstacles to overcome, like varying patient reactions, possible adverse effects, and legal restrictions. Cannabis has the potential to be a key component in the treatment of MS-related spasticity with additional research and the creation of standardised treatment protocols.