Introduction

Multiple Sclerosis (MS)¹ is an autoimmune disease caused by the destruction of myelin around nerve fibres within the central nervous system. This inhibits the flow of information from the brain to the body. Several types of symptoms have been linked to the presence of MS, such as muscle spasms, pain, fatigue, and mobility difficulties, characterised as the most common symptomatology, very considerably impairing the quality of life in patients with this disease.

In the past few years, there has been a growing interest in cannabis-based therapies, which have been utilised as treatments in managing MS symptoms. Cannabis contains compounds such as THC and CBD that have been proven to cause relaxation in muscle spasms, relieve pain, and improve sleep in patients with MS. The clinical potential of cannabis remains to be fully understood, and research studies suggest that it may be helpful in those conditions in which currently available conventional treatment cannot cure. The use of cannabis in medicine, particularly in MS, remains a subject of controversy. Therefore, further clinical research must be done to better understand its benefits and side effects. This article aims to provide an overview of the array of research into cannabis-based Multiple Sclerosis therapies.

Cannabis compounds relevant to multiple sclerosis treatment

Cannabinoids² consist of various compounds, two of which are the most prevalent: THC (tetrahydrocannabinol) and CBD (cannabidiol). Both of these chemicals interact with the endocannabinoid system (ECS) of the body. The ECS can be regarded as a network of two forms of receptors known as CB1 and CB2, which regulate normal processes such as pain, inflammation, and immune reactions. This system is very important in treating symptoms of multiple sclerosis.³ THC binds mainly to CB1 receptors in the central nervous system and the brain, where it produces psychoactive effects. It has been shown to have the ability to control spasticity, stiffness, and pain from spasm in patients with MS. The above interactions at the receptor sites decrease those neurological manifestations that lead to discomfort and hinder mobility in the patient.⁴

CBD interacts, on the other hand, with CB2 receptors, mainly located within the immune system. Its anti-inflammatory and neuroprotective features may further inhibit the immune system from causing its toxins to further destroy nerve cells and may improve the symptoms and delay the progression of the disease.

The emerging research identifies other minor cannabinoids such as CBG (cannabigerol), CBN (cannabinol) and terpenes as supportive for enhancing symptom relief. The pharmacological concept is known as the entourage effect,⁵ an interactive effect of these compounds that acts synergistically, amplifying the actual therapeutic benefits of cannabis.

Current research findings 

Sativex (nabiximols)⁶ is an oral cannabis extract spray approved for treating spasticity caused by multiple sclerosis. Consisting of equally balanced preparation containing THC (tetrahydrocannabinol) and CBD, it reduces the physical symptoms such as stiffness of muscles, pain, and even the limitation of mobility. Notably, clinical trials have demonstrated a decrease in spasticity for patients, and other symptoms such as pain, difficulty in walking, and daily spasms and incontinence also improved.

The present studies also indicate that Sativex not only relieves symptoms but also impacts cortical and spinal excitability. It enhances SICI and reduces IC. These findings indicate its role in the activity of circuits governing the inhibition process in the brain. SICI refers to the strength of neurons in inhibiting others and is crucial for the control of muscle tone and spasticity. However, this may alleviate the excessive muscle contraction, common in MS, with Sativex treatment. On the contrary, ICF reduction or facilitation in excitatory pathways means Sativex decreases their overactivity and is thus therapeutically effective.

In contrast, studies of smoked cannabis⁷ revealed some positive effects on treatment-resistant spasticity and pain in MS patients, although cognitive effects were reported. While the inconsistently modest results from orally administered cannabinoids, such studies have shown a considerable reduction in pain and spasticity.

The acute cognitive effects seen with smoked cannabis were crossed with participants remaining within normal cognitive ranges. As such, these findings may contribute support for the use of cannabis-based therapies like Sativex and smoked cannabis as a viable management tool for MS symptoms, although long-term cognitive impact research is ultimately required.

Challenges and gaps in research

Among the main challenges hindering broader acceptance of cannabis in the therapeutic practice for such conditions as MS, there appears to be a lack of standardisation, that is, varieties of cannabis strain, dosage, and delivery may cause inconsistent effects for therapy. With many cannabinoids and terpenes at different levels in different strains, side effects and efficacy could be influenced, putting healthcare providers in challenging positions regarding prescriptions.⁸

Furthermore, difficulty in reproduction goes hugely against what seems to be a strong evidence base from cannabis therapy. Clinical studies are often too small or lack enough control groups to allow for comparison of outcomes between studies, which also makes generalisation to the greater MS population problematic.

Legal and regulatory restrictions also muddy the playing field for cannabis research and treatment. International regulations on cannabis differ from one jurisdiction to the next, with issues over financing its research, access, and possibilities concerning legality in study conduct. In some countries, it is not even legal or is strictly controlled, meaning that patients will not be able to get access to the said treatment and health professionals may not even prescribe the substance at all.⁹

Lastly, there is limited long-term safety data regarding the psychological effects of cannabis use. Concerns of potential dependence and abuse in patients with a history of drug use disorders have remained a constant theme. All these considerations hence call for research and standardisation in the administration of cannabis therapy to ensure safe and effective treatment in patients suffering from MS and other conditions. These challenges will continue to be critical in making the clinical practice of cannabis in medicine advance effectively.

Future directions for research

Key strategies to further develop cannabis-based treatments in MS should therefore focus on expanded clinical trials with better, larger, and diverse populations to allow understanding of efficacy across different populations. This should, therefore, help differentiate the variations in response based on age, sex, or even disease progression. In addition, studies are needed on long-term consequences, safety, and dosing recommendations.¹⁰ The clear delineation of dosing parameters will help healthcare providers prescribe cannabis with more comfort and in a safe manner. Critical to a comprehensive treatment is understanding how MS symptoms change over time when cannabis is used.

Novel drug delivery mechanisms, such as transdermal patches or inhalers,¹¹ can improve bioavailability, increase the speed of onset, and facilitate improved patient compliance and satisfaction. Precision medicine approaches will also enable personalisation of cannabis treatment based on genetics and individual patient preferences. Lastly, the potential of cannabis in combination with the existing drugs, such as immunomodulatory,¹² may provide additive results, meaning better overall outcomes, as well as reduced side effects of the combination.

Collectively, these approaches will have the potential to take the clinical use of cannabis in MS forward, thereby ensuring that the patients are offered safe and effective, as well as personalised, treatment options.

Ethical, legal and social considerations

Improving access and reducing cost are essential challenges to making cannabis therapy available for patients with MS. Most insurance plans do not include these therapies. This can be quite impactful for resource-limited individuals, translating into unequal access, hurting marginalised groups who are already disadvantaged in accessing healthcare services.

Added to such difficulties is the stigma attached to cannabis use, preventing a large number of patients from pursuing these treatments. Misconceptions about cannabis being a recreational substance rather than a legitimate treatment may contribute to unawareness about therapeutic potential for non-users, reluctance to discuss with health care providers, or social isolation.

Patient advocacy plays an important role in these issues by letting patients and caregivers know the benefits and costs associated with cannabis therapy, prognosis and side effects through policy changes and healthcare communication, which will improve access and insurance coverage. For instance, open dialogue and patient education among providers help reduce stigma and increase equity in accessing cannabis so that patient outcomes related to MS improve as well.

Summary

• MS is an autoimmune disease which causes destruction of myelin around nerve fibres, producing multiple symptoms, such as spasms in the muscles, pain, fatigue, and mobility disorders
• In the past few decades, research has focused on the treatment with cannabis-based medicine because of chemical constituents, including THC and CBD, which ease some of these symptoms.
• The oral cannabis extract spray was used to prepare the spray Sativex with a combination of THC and CBD that reduced spasticity and all its secondary symptoms
• Major challenges to cannabis-based therapy include: variability in strains and dosages, regulatory barriers and limited long-term safety information about potential psychological effects and dependency
• Phase III trials should be conducted on a more diverse population for efficacy and safety definition over time. Promoting conversations about access and affordability to reduce stigma and focus on patient advocacy will enhance the acceptance of cannabis therapies for MS patients