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

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to compare the effects of cannabidiol (CBD), tetrahydrocannabinol (THC), or both, on sleep and pain in persons with multiple sclerosis (MS). Little is known about how CBD and/or THC may help sleep, reduce pain, or perhaps even treat pain through better sleep.

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.

What data supports the effectiveness of the drug CBD + THC for Multiple Sclerosis symptoms?

Research suggests that CBD, a component of the drug, has anti-inflammatory properties and may help reduce symptoms in a mouse model of Multiple Sclerosis. Additionally, a combination of THC and CBD has been used to manage spasticity, a common symptom in MS patients. ^{1 2 3 4 5}

Is the combination of CBD and THC safe for humans, particularly for those with multiple sclerosis?

The combination of CBD and THC, as found in Sativex, has been studied for safety in people with multiple sclerosis. Most side effects were mild to moderate, with dizziness and fatigue being the most common. Serious side effects were rare, and no new safety concerns were identified with long-term use. ^{1 3 4 6 7}

How is the CBD + THC drug unique for treating multiple sclerosis symptoms?

The CBD + THC drug is unique because it combines cannabidiol (CBD), known for its anti-inflammatory and immunosuppressive properties, with tetrahydrocannabinol (THC) in an oromucosal spray form, specifically targeting spasticity in multiple sclerosis patients who do not respond to other treatments. ^{1 4 7 8 9}

Research Team

Tiffany Braley

Principal Investigator

University of Michigan

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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 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 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 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]

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

Immunomodulatory Potential of Cannabidiol in Multiple Sclerosis: a Systematic Review. [2023]

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

Tetrahydrocannabinol/Cannabidiol Oromucosal Spray in Patients With Multiple Sclerosis: A Pilot Study on the Plasma Concentration-Effect Relationship. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

A new formulation of cannabidiol in cream shows therapeutic effects in a mouse model of experimental autoimmune encephalomyelitis. [2018]

4. Spain pubmed.ncbi.nlm.nih.gov

Clinical experiences with cannabinoids in spasticity management in multiple sclerosis. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Cannabidiol Attenuates Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis Through Induction of Myeloid-Derived Suppressor Cells. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis. [2022]

7. England pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Nabiximols discontinuation rate in a large population of patients with multiple sclerosis: a 18-month multicentre study. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

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