CBD + THC for Multiple Sclerosis Symptoms

Overseen By David Johnson

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Tiffany J. Braley, MD, MS

Must not be taking: Cannabinoids, Warfarin, Valproate, others

Disqualifiers: Severe depression, Schizophrenia, Cardiovascular, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

166 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how CBD (Cannabidiol) and THC (Tetrahydrocannabinol), either alone or combined, can help people with multiple sclerosis (MS) improve sleep and reduce pain. Researchers aim to determine if these treatments can also ease pain through improved sleep. The trial seeks participants with MS who have experienced moderate to severe pain for at least three months. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires participants to maintain a stable pain medication regimen during the study. However, you must stop using cannabinoids 30 days before the study and avoid certain medications like warfarin, valproate, clobazam, and others that interact with the study drugs.

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

Research has shown that both CBD and THC have been studied for their safety in people with multiple sclerosis (MS). Medical cannabis oils containing CBD and THC have been found to be safe and well-tolerated. These studies indicate they can help reduce pain, muscle stiffness, and sleep problems in people with MS.

Specifically for CBD, research suggests it may help lessen stiffness and discomfort. However, more than 10% of people using cannabis, including CBD, reported side effects such as dizziness and dry mouth.

For THC, studies have not identified any major safety concerns. Patients generally found THC helpful for managing their symptoms. Like CBD, common side effects include dizziness and dry mouth.

The combination of CBD and THC has also been tested and appears to be a safe and well-tolerated option for managing muscle stiffness in MS.

While these findings are promising, consulting a healthcare provider before joining any clinical trial is important to ensure it is a safe choice for individual health needs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for multiple sclerosis, which often include medications like interferons or monoclonal antibodies, the treatments in this trial involve cannabinoids, specifically Cannabidiol (CBD) and Tetrahydrocannabinol (THC). Researchers are excited about these treatments because they tap into the body's endocannabinoid system, which may help in managing symptoms like pain and muscle spasticity differently than traditional therapies. CBD and THC offer a novel approach by potentially providing symptom relief with a different mechanism of action compared to existing drugs. Additionally, combining both CBD and THC may enhance therapeutic effects while minimizing side effects, offering a more balanced treatment option.

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

Research has shown that both cannabidiol (CBD) and tetrahydrocannabinol (THC) may benefit people with multiple sclerosis (MS). Studies indicate that CBD can reduce muscle tightness and pain, common symptoms of MS. THC has also improved muscle stiffness and pain, aiding many patients. In this trial, participants will join different treatment arms to evaluate these effects. One arm will receive CBD with a placebo for THC, another will receive THC with a placebo for CBD, and a third arm will receive both CBD and THC together. These findings suggest that CBD and THC could effectively manage MS-related symptoms, particularly pain and sleep problems. ^{1 4 6 7 8}

Who Is on the Research Team?

Tiffany Braley

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for people with multiple sclerosis (MS) who have had moderate to severe chronic pain for at least 3 months. They must be on a stable MS medication without liver issues and agree to keep their pain treatment the same during the study. People can't join if they use certain drugs, have serious heart problems, are pregnant or breastfeeding, have a history of drug abuse or certain mental health conditions, or work in jobs that require alertness.

Inclusion Criteria

I have MS and have been on a stable medication dose for 3+ months without liver issues.

Willingness to maintain stable analgesic regimen during study period

Recent serum aspartate transaminase, alanine transaminase, and bilirubin testing within 90 days of screening

Exclusion Criteria

I don't have any health conditions that could risk my safety in the trial.

I am currently experiencing severe depression.

I am not currently using any strong CYP2C19 drugs, except for certain allowed medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either CBD, THC, both, or placebo to assess effects on sleep and pain

12 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cannabidiol (CBD)
• Tetrahydrocannabinol (THC)

Trial Overview

The study tests how CBD and THC affect sleep and pain in MS patients. Participants will receive either CBD, THC, both, or placebos to see if these substances improve sleep quality and reduce pain levels.

How Is the Trial Designed?

Group I: Cannabidiol (CBD) Experimental Treatment 2 Interventions

Cannabidiol (Epidiolex® 100 mg/mL solution) will initially be prescribed as 50 mg (0.5 mL) twice daily during the first seven days of active treatment (half of full anticipated dose), followed by 100 mg (1 mL) twice daily for the remainder of the treatment interval (full dose). PLUS Placebo Tetrahydrocannabinol (TCH) capsules which contain no active ingredients. Matching placebo capsules will be taken twice per day in the same schedule and manner as active dronabinol.

Group II: Tetrahydrocannabinol (THC) Active Control 2 Interventions

Tetrahydrocannabinol (Dronabinol capsules) will initially be prescribed as 2.5 mg twice daily during the first seven days of active treatment (half of full anticipated dose), followed by 5 mg twice daily for the following days of active treatment (full dose). PLUS Placebo CBD (A matching placebo oral solution to Epidiolex® will be used that consists of all of the excipients in the active solution without the cannabidiol component). The placebo will be dosed in the same schedule and manner as active Epidiolex®.

Group III: CBD + THC Active Control 2 Interventions

Cannabidiol (Epidiolex® solution) will initially be prescribed as 50 mg (0.5 mL) twice daily during the first seven days of active treatment (half of full anticipated dose), followed by 100 mg (1 mL) twice daily for the remainder of the treatment interval (full dose). PLUS Tetrahydrocannabinol (Dronabinol capsules) will initially be prescribed as 2.5 mg twice daily during the first seven days of active treatment (half of full anticipated dose), followed by 5 mg twice daily for the following days of active treatment (full dose).

Group IV: Placebo CBD + Placebo THC Placebo Group 2 Interventions

Placebo CBD (A matching placebo oral solution to Epidiolex® will be used that consists of all of the excipients in the active solution without the cannabidiol component). The placebo will be dosed in the same schedule and manner as the active CBD. PLUS Placebo Tetrahydrocannabinol (TCH) capsules which contain no active ingredients. Matching placebo capsules will be taken twice per day in the same schedule and manner as active drug.

Cannabidiol (CBD) is already approved in United States, European Union for the following indications:

Approved in United States as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in European Union as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Who Is Running the Clinical Trial?

Tiffany J. Braley, MD, MS

Lead Sponsor

Trials

1

Recruited

170+

National Center for Complementary and Integrative Health (NCCIH)

Collaborator

Trials

886

Recruited

677,000+

Published Research Related to This Trial

In a study of 50 patients with multiple sclerosis, the combination of THC and CBD was effective in reducing spasticity in 80% of cases, suggesting it could be a beneficial alternative treatment for this symptom.

The treatment had an acceptable safety profile, with adverse effects reported in a minority of patients, including dizziness and somnolence, indicating that while some side effects occurred, they were manageable and did not outweigh the benefits for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experiences with cannabinoids in spasticity management in multiple sclerosis. Lorente Fernández, L., Monte Boquet, E., Pérez-Miralles, F., et al.[2022]

In a 6-week randomized controlled trial, Sativex, which contains THC and CBD, significantly improved spasticity in patients with multiple sclerosis, with a mean treatment exposure of 334 days in the follow-up safety trial involving 146 patients.

The treatment was generally well-tolerated, with most adverse events being mild to moderate, and no new safety concerns were identified; serious adverse events were rare, and there was no evidence of developing tolerance to the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis. Serpell, MG., Notcutt, W., Collin, C.[2022]

In a pilot study involving 12 patients with multiple sclerosis, the use of a THC/CBD oromucosal spray significantly reduced spasticity symptoms, as indicated by a decrease in the Numerical Rating Scale (NRS) scores from a median of 6 to 3.5 (P < 0.001).

The study found a significant correlation between the plasma concentrations of THC and CBD and the reduction in spasticity, suggesting that higher levels of these cannabinoids in the blood are associated with greater clinical effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetrahydrocannabinol/Cannabidiol Oromucosal Spray in Patients With Multiple Sclerosis: A Pilot Study on the Plasma Concentration-Effect Relationship. Contin, M., Mancinelli, L., Perrone, A., et al.[2018]

In a study of 1845 Italian patients with multiple sclerosis, 81.4% experienced a significant improvement in spasticity after using the THC:CBD oromucosal spray, with a notable reduction in symptoms observed at both 4 weeks and 72 weeks.

Despite the initial effectiveness, nearly 50% of patients discontinued the therapy by 18 months, primarily due to loss of efficacy or adverse events, highlighting the need for ongoing evaluation of treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nabiximols discontinuation rate in a large population of patients with multiple sclerosis: a 18-month multicentre study. Chisari, CG., Solaro, C., Annunziata, P., et al.[2021]

Cannabidiol (CBD) shows strong potential as an effective treatment for multiple sclerosis (MS) in animal models, particularly for its anti-inflammatory and immunosuppressive properties, with excellent tolerability even at high doses.

However, clinical evidence in humans is limited and often negative, suggesting a need for more studies with optimized dosing and better-defined efficacy endpoints to fully understand CBD's effects in MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulatory Potential of Cannabidiol in Multiple Sclerosis: a Systematic Review. Furgiuele, A., Cosentino, M., Ferrari, M., et al.[2023]

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 mouse model of multiple sclerosis, cannabidiol (CBD) treatment significantly reduced symptoms of the disease, including paralysis and T cell infiltration in the central nervous system, indicating its potential as an anti-inflammatory agent.

CBD treatment increased the number of myeloid-derived suppressor cells (MDSCs), which were crucial for inhibiting T cell activity and contributed to the observed reduction in disease severity, highlighting a novel mechanism of action for CBD in managing neuroinflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Attenuates Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis Through Induction of Myeloid-Derived Suppressor Cells. Elliott, DM., Singh, N., Nagarkatti, M., et al.[2022]

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]

Topical application of a 1% CBD-cream significantly reduced the clinical symptoms of autoimmune encephalomyelitis (EAE) in mice, improving hind limb paralysis and decreasing disease severity compared to untreated EAE mice.

The CBD-cream treatment also showed neuroprotective effects by reducing inflammation markers and T cell activation in the spinal cord and spleen, suggesting its potential as a therapeutic option for managing multiple sclerosis symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new formulation of cannabidiol in cream shows therapeutic effects in a mouse model of experimental autoimmune encephalomyelitis. Giacoppo, S., Galuppo, M., Pollastro, F., et al.[2018]

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