Cannabis for Multiple Sclerosis

(CANSEP Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Pierre Duquette, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) afflicting over 77,000 Canadians. Unfortunately, the therapeutic arsenal to relieve MS symptoms is limited. It is therefore essential to develop better approaches to treat the symptoms of MS. The use of cannabis for recreational purposes is now legal in Canada. However, for many years, people with Multiple Sclerosis (PwMS) have used cannabis either to relax, to reduce pain and spasticity, or to improve sleep and daily functioning. Currently, there is little scientifically established evidence that cannabis works on these symptoms in people with MS. It is therefore important to carry out studies to better understand the efficacy Δ-9-tetrahydrocannabinol (THC), and cannabidiol (CBD) on MS symptoms . THC is known for its analgesic, neuroprotective and anti-inflammatory properties and CBD seems to have positive effects on anxiety and cognitive abilities (memory, concentration). For this study, investigators hypothesize that administering different doses of THC alone, CBD alone, and THC and CBD combined will result in a significant beneficial effect on spasticity relief compared to placebo.

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.

What data supports the effectiveness of the drug for treating multiple sclerosis?

Research shows that nabiximols (Sativex), a spray containing THC and CBD, is effective in treating spasticity (muscle stiffness) in multiple sclerosis patients. It has also been studied for its effects on pain and bladder issues, with generally mild side effects. ^{1 2 3 4 5}

Is cannabis-based treatment safe for humans, particularly for those with multiple sclerosis?

Cannabis-based treatments like Sativex (THC:CBD oromucosal spray) have been used by over 45,000 patients and are generally well-tolerated, with common side effects including dizziness and fatigue. Serious side effects are rare, and there is no evidence of abuse or dependence, but some patients may experience psychiatric issues or falls. Long-term safety data supports its use, but potential for dependence and long-term effects are still being studied. ^{1 4 5 6 7}

How is the drug Sativex unique for treating multiple sclerosis?

Sativex is unique because it is an oromucosal spray containing a balanced mix of THC and CBD, specifically designed to manage spasticity, pain, and bladder dysfunction in multiple sclerosis patients who do not respond well to other treatments. Unlike many oral medications, it has shown good long-term tolerability with mild to moderate side effects. ^{1 3 5 8 9}

Research Team

Pierre Duquette, MD

Principal Investigator

Centre hospitalier de l'Université de Montréal (CHUM)

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Cannabis oil (Cannabinoid)

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.

Participant Groups

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 for the following indications:

Approved in Canada as Cannabis oil for:

• Pain relief
• Spasticity relief
• Sleep improvement

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Dr. Réjean Lapointe

Centre hospitalier de l'Université de Montréal (CHUM)

Chief Medical Officer since 2023

MD from Université de Montréal

Dr. Fabrice Brunet

Centre hospitalier de l'Université de Montréal (CHUM)

Chief Executive Officer since 2015

MD from Université de Montréal

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Dr. Paul C. Hébert

Canadian Institutes of Health Research (CIHR)

Chief Executive Officer

MD, University of Ottawa

Dr. Paul C. Hébert

Canadian Institutes of Health Research (CIHR)

Chief Medical Officer

MD, University of Ottawa

Multiple Sclerosis Society of Canada

Collaborator

Trials

17

Recruited

990+

Findings from Research

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

The influence of physiotherapy intervention on patients with multiple sclerosis-related spasticity treated with nabiximols (THC:CBD oromucosal spray). [2020]

2. United States pubmed.ncbi.nlm.nih.gov

The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of cannabinoid oromucosal spray for multiple sclerosis spasticity. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Resting-state functional connectivity in multiple sclerosis patients receiving nabiximols for spasticity. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Evaluation of the tolerability and efficacy of Sativex in multiple sclerosis. [2017]

6. New Zealand 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. [2022]

7. Canada pubmed.ncbi.nlm.nih.gov

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

8. Switzerland pubmed.ncbi.nlm.nih.gov

Tetrahydrocannabinol:Cannabidiol Oromucosal Spray for Multiple Sclerosis-Related Resistant Spasticity in Daily Practice. [2022]

9. Switzerland 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. [2018]