Cannabis for Multiple Sclerosis

(CANSEP Trial)

Overseen By Amel Zertal

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Must not be taking: Cannabis, Cannabinoids, Botulinum toxin, others

Disqualifiers: Schizophrenia, Epilepsy, Cardiac dysfunction, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different cannabis oils might help people with multiple sclerosis (MS) manage muscle stiffness, known as spasticity. Researchers are testing three treatment options: THC alone, CBD alone, and a combination of both, to determine which is most effective compared to a placebo. People diagnosed with MS for at least six months and experiencing spasticity not relieved by their current treatment might be suitable for this trial. The study aims to provide clearer evidence on whether cannabis can effectively ease MS symptoms like muscle stiffness. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of your current standard therapies for at least 30 days before starting and throughout the study. However, you must stop using cannabis or cannabinoid-based medications at least 7 days before the study and for its duration.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cannabis treatments, such as THC and CBD, are generally safe for treating multiple sclerosis (MS) symptoms.

For THC alone, studies found that while some side effects might occur, they are usually mild to moderate and dose-dependent. No major safety issues were reported, making THC a well-tolerated option for many patients.

CBD alone also appears safe and well-tolerated in MS patients. It has been linked to reducing symptoms like muscle stiffness and pain, with few safety concerns.

When combined, THC and CBD remain well-tolerated, according to research. This combination may even reduce some unwanted effects, like feeling overly happy, while enhancing symptom relief.

Overall, these findings support the safety of cannabis-based treatments for MS, especially when used in controlled doses. However, individual responses can vary with any treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike traditional treatments for multiple sclerosis (MS) that often focus on immune system modulation or symptom management, cannabis oil offers a unique approach by potentially easing symptoms through its active compounds, THC and CBD. Researchers are particularly excited about THC and CBD because they target the body's endocannabinoid system, which may help in reducing inflammation and pain more naturally. The combination of THC and CBD may offer a synergistic effect, potentially enhancing the therapeutic benefits compared to using either compound alone. Plus, the treatment is administered in easy-to-take softgel capsules, offering a convenient and controlled way to manage dosing.

What evidence suggests that this trial's treatments could be effective for multiple sclerosis?

Research has shown that THC (tetrahydrocannabinol) can reduce muscle stiffness and pain in people with multiple sclerosis (MS). One study found that taking cannabis orally doubled the relief from muscle stiffness. In this trial, some participants will receive THC alone. CBD (cannabidiol) also effectively addresses muscle spasms and pain, especially when the mix contains more CBD than THC. Another group in this trial will receive CBD alone. Real-life evidence indicates that using both THC and CBD together works well and is safe for managing severe MS symptoms. This trial will also include a group receiving both THC and CBD together. These findings suggest that cannabis, whether THC, CBD, or both, could help relieve MS-related muscle stiffness. ^{1 6 7 8 9}

Who Is on the Research Team?

Pierre Duquette, MD

Principal Investigator

Centre hospitalier de l'Université de Montréal (CHUM)

Are You a Good Fit for This Trial?

This trial is for adults over 21 with Multiple Sclerosis (MS) who experience spasticity not relieved by current therapy. Participants must have stable MS treatments for the last 30 days and be able to follow study procedures. They should not have severe psychiatric disorders, substance abuse issues, significant liver or heart problems, or plans to conceive.

Inclusion Criteria

I can speak and read English or French at a ninth-grade level.

I am 21 years old or older.

My MS-related muscle stiffness has been severe for over a month and current treatments aren't helping.

Exclusion Criteria

My kidney function is reduced with a creatinine clearance below 50 ml/min.

My liver isn't working well, as shown by tests being three times above the normal limit.

I am a man with fertility issues and plan to have children in the future.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive THC, CBD, or a combination, or placebo for 4 weeks, with dose escalation if tolerated

4 weeks

Weekly visits (in-person) with courtesy calls between visits

Extended Treatment

Responders continue treatment for an additional 12 weeks

12 weeks

Monthly visits (in-person) with courtesy calls between visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cannabis oil

Trial Overview

The study tests whether cannabis oil containing different doses of THC alone, CBD alone, or both combined can help relieve spasticity in MS compared to a placebo. The effectiveness of these cannabinoids on symptoms like pain and cognitive abilities will also be evaluated.

How Is the Trial Designed?

Group I: THC and CBD combined Experimental Treatment 1 Intervention

* Dosage form : Softgel * Dosage \& frequency : 40 mg /day of CBD up to 200 mg and 4 mg /day of THC up to 20 mg in two doses a day * Duration : 4 weeks of treatment followed by 12 additional weeks of follow up.

Group II: THC alone Experimental Treatment 1 Intervention

* Dosage form : Softgel * Dosage \& frequency : 4 mg /day of THC up to 20 mg in two doses a day * Duration : 4 weeks of treatment followed by 12 additional weeks of follow up.

Group III: CBD alone Experimental Treatment 1 Intervention

* Dosage form : Softgel * Dosage \& frequency : 40 mg /day of CBD up to 200 mg in two doses a day * Duration : 4 weeks of treatment followed by 12 additional weeks of follow up.

Group IV: Placebo Placebo Group 1 Intervention

* Dosage form : Softgel * Dosage \& frequency : caps of placebo twice a day * Duration : 4 weeks of treatment followed by 12 additional weeks of follow up.

Cannabis oil is already approved in Canada, European Union for the following indications:

Approved in Canada as Cannabis oil for:

• Pain relief
• Spasticity relief
• Sleep improvement

Approved in European Union as Nabiximols for:

• Moderate to severe muscle spasticity in MS

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Multiple Sclerosis Society of Canada

Collaborator

Trials

17

Recruited

990+

Published Research Related to This Trial

In a study of 297 patients with moderate to severe MS-related spasticity, nabiximols (Sativex) demonstrated significant effectiveness, with a mean reduction in spasticity scores from 7.6 to 5.5 over 12 weeks.

Patients undergoing physiotherapy alongside nabiximols treatment had a higher likelihood of achieving clinically relevant improvement and were less likely to discontinue treatment, indicating that combining PT with nabiximols may enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of physiotherapy intervention on patients with multiple sclerosis-related spasticity treated with nabiximols (THC:CBD oromucosal spray). Grimaldi, AE., De Giglio, L., Haggiag, S., et al.[2020]

In a study of 1615 Italian patients with multiple sclerosis, Sativex (a THC:CBD oromucosal spray) demonstrated significant effectiveness, with 70.5% of patients achieving at least a 20% improvement in spasticity after one month of treatment.

Despite its effectiveness, 39.5% of patients discontinued Sativex within six months, primarily due to lack of effectiveness or adverse events, indicating the need for careful monitoring of patient responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of cannabinoid oromucosal spray for multiple sclerosis spasticity. Patti, F., Messina, S., Solaro, C., et al.[2022]

In a study of 12 multiple sclerosis patients treated with nabiximols (Sativex®), 58.3% showed a significant reduction in spasticity, indicating its potential efficacy in managing MS-related symptoms.

Functional MRI analysis revealed that nabiximols treatment was linked to increased global brain connectivity, particularly in responders, and changes in connectivity in motor areas and the cerebellum, suggesting a possible mechanism of action for its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resting-state functional connectivity in multiple sclerosis patients receiving nabiximols for spasticity. Gajofatto, A., Cardobi, N., Gobbin, F., et al.[2023]

Sativex® (THC:CBD) has been used for over 45,000 patient-years in treating treatment-resistant spasticity in multiple sclerosis, with a registry study involving 941 patients showing that 83% reported benefits from the treatment.

The long-term safety profile of Sativex® appears consistent with known safety data, with only 6% of patients experiencing significant psychiatric adverse events and no new long-term safety concerns identified, indicating it is well-tolerated for MS spasticity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An observational postmarketing safety registry of patients in the UK, Germany, and Switzerland who have been prescribed Sativex® (THC:CBD, nabiximols) oromucosal spray. Etges, T., Karolia, K., Grint, T., et al.[2022]

Cannabinoids, including pharmaceutical options like nabiximols and nabilone, show sufficient evidence for effectively managing pain and spasticity in multiple sclerosis (MS) based on a review of 11 systematic reviews and 32 studies.

While cannabinoids may have modest effects on MS symptoms, further research is needed, particularly studies comparing cannabinoids to non-cannabinoid treatments to fill existing evidence gaps.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews. Nielsen, S., Germanos, R., Weier, M., et al.[2023]

In a study of 241 patients with multiple sclerosis spasticity, the THC:CBD oromucosal spray significantly improved spasticity symptoms compared to placebo, regardless of the number of previous ineffective treatments.

The spray not only enhanced spasticity-related symptoms like sleep quality and walking speed but also demonstrated good tolerability, indicating it is a safe add-on treatment option for patients with a history of failed antispasticity therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of Previous Failed Antispasticity Therapy on the Efficacy and Tolerability of THC:CBD Oromucosal Spray for Multiple Sclerosis Spasticity. Haupts, M., Vila, C., Jonas, A., et al.[2018]

Sativex, a cannabis-based oromucosal spray containing THC and CBD in a 1:1 ratio, has shown significant effectiveness in reducing neuropathic pain and other symptoms like spasticity in patients with multiple sclerosis, based on five randomized controlled trials involving 368 patients.

While Sativex is effective for managing certain neurological symptoms, common side effects include dizziness, sleepiness, and fatigue, and the long-term safety and potential for dependence remain uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sativex for the management of multiple sclerosis symptoms. Perras C, .[2016]

In a study involving 433 patients with drug-resistant spasticity due to multiple sclerosis, the THC:CBD oromucosal spray (Sativex®) significantly improved spasticity and related symptoms after 3 months of treatment, enhancing quality of life and daily activities.

The treatment was well-tolerated, with only 10.4% of patients reporting adverse events, none of which were severe, indicating a favorable safety profile in everyday clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetrahydrocannabinol:Cannabidiol Oromucosal Spray for Multiple Sclerosis-Related Resistant Spasticity in Daily Practice. Vermersch, P., Trojano, M.[2022]

Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in the form of Sativex has shown therapeutic effects on refractory spasticity, central neuropathic pain, and bladder dysfunction in multiple sclerosis patients, addressing common symptoms that current oral medications struggle to effectively manage.

The use of THC/CBD is generally well-tolerated, with most adverse effects being mild to moderate, and a low rate of discontinuation suggests good long-term safety for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the tolerability and efficacy of Sativex in multiple sclerosis. Moreno Torres, I., Sanchez, AJ., Garcia-Merino, A.[2017]

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