Multiple Sclerosis and Complementary Health Approaches: What the Science Says

Cannabinoids

Orally administered cannabinoids (cannabis extract, synthetic tetrahydrocannabinol [THC]), mucosally delivered cannabinoids (cannabis THC and cannabidiol [CBD] extract oral spray, nabiximols (brand name Sativex)), and smoked cannabis have all been studied for therapeutic effects in MS. 

Based on available evidence, cannabinoids may relieve spasticity and/or pain in people with MS; however, no marijuana-derived medications are approved by the U.S. Food and Drug Administration (FDA) to treat MS. Sativex (equal mix of THC and CBD) has received regulatory approval in several European countries, including Spain, and Canada for the treatment of spasticity (muscle stiffness/spasm) due to MS. 

There is insufficient data to determine if smoking marijuana ameliorates symptoms of MS. Additionally, the psychoactive properties and other potential adverse effects need to be considered.

What Does the Research Show?

• A 2022 Cochrane review of 25 randomized controlled trials involving a total of 3,763 participants found that compared with placebo, nabiximols probably reduces the severity of spasticity in the short term in people with MS. The reviewers were less certain about the effect on chronic neurological pain and health-related quality of life. A 2018 systematic review and meta-analysis of 17 trials involving a total of 3,161 participants found limited efficacy of cannabinoids such as THC, CBD, THC:CBD formulations, pharmaceutical cannabinoids (dronabinol and nabilone), smoked cannabis, and oral cannabinoid extracts for the treatment of spasticity, pain, and bladder dysfunction in patients with MS. Another 2018 systematic review of 11 reviews providing data from 32 studies (including 10 moderate-to-high quality randomized controlled trials) found sufficient evidence that cannabinoids may be effective for symptoms of pain and/or spasticity in MS. Results from a 2024 randomized controlled trial involving 68 participants did not indicate a significant treatment effect on spasticity using a clinician-rated measure of velocity-dependent lower limb muscle tone.
• Oral cannabinoids. The 2014 evidence-based guidelines issued by the American Academy of Neurology, which were reaffirmed in 2023, concluded that oral cannabis extract is established as effective for reducing patient-reported spasticity symptoms and pain. This subjective benefit is possibly maintained for 1 year. The guidelines also concluded that THC is probably effective for reducing patient-reported symptoms of spasticity and pain. This subjective benefit is possibly maintained for 1 year. However, the guidelines state that oral cannabis extract and THC are probably ineffective for reducing both objective spasticity measures and MS-related tremor symptoms. Oral cannabis extract and THC are possibly effective for reducing symptoms and objective measures of spasticity over 1 year.
• Oromucosal cannabinoid spray. The 2014 American Academy of Neurology evidence-based guidelines, which were reaffirmed In 2023, concluded that Sativex oromucosal cannabinoid spray is probably effective for improving subjective spasticity symptoms and is probably ineffective for reducing objective spasticity measures over 6 weeks or bladder incontinence episodes over 10 weeks. Further, the guidelines state that Sativex oromucosal spray is possibly ineffective for reducing MS-related tremor over 15 weeks. In addition, a 2010 meta-analysis reported on 666 patients with MS who were given either nabiximols (363) or placebo (303); all the patients had spasticity that was not well controlled using existing treatments. Results showed nabiximols effects are typically seen within 3 weeks. Furthermore, about one-third of the MS patients given nabiximols had a 30 percent improvement from baseline. The authors noted the treatment appeared reasonably safe.
• Smoked cannabis. Based on two small studies, the 2014 evidence-based guidelines issued by the American Academy of Neurology, which were reaffirmed in 2023, concluded that data are inadequate to determine the safety or efficacy of smoked cannabis used for spasticity/pain, balance/posture, and cognition.

Safety

• In the studies that were the basis for the 2014 American Academy of Neurology guidelines, which were reaffirmed in 2023, cannabinoids were generally well tolerated, although some serious adverse effects were reported. Mild or moderate side effects including dizziness, somnolence, drowsiness, lightheadedness, memory disturbance, and difficulty concentrating were more common in participants receiving cannabinoids vs placebo. Less common effects included increased appetite, nausea, vomiting, constipation, dry/sore mouth, myalgia, seizures, and others. The guidelines noted that because cannabinoids have known psychoactive properties, their potential for psychopathologic and neurocognitive adverse effects is a concern, especially in a patient population that may be vulnerable due to underlying disorders.
• The guidelines recommend that clinicians counsel patients about the potential for psychopathologic/cognitive and other adverse events associated with cannabinoids. Sativex oromucosal cannabinoid spray is not approved by the FDA and is unavailable in the United States. Further, the guidelines suggest caution should be exercised with regard to extrapolation of results of trials of standardized oral cannabis extract (which are unavailable commercially) to other nonstandardized, nonregulated cannabis extracts (which may be commercially available in states with medical marijuana laws).
• Although people sometimes think that CBD products are completely safe, they may not be. Unlike Epidiolex (the purified CBD product sold as an FDA-approved prescription drug), over-the-counter CBD products may contain more or less CBD than stated on their labels, and because of inadequate quality control, they may also contain contaminants, such as THC. 

Ginkgo biloba

According to clinical practice guidelines issued by the American Academy of Neurology in 2014 and reaffirmed in February 2023, there is strong evidence that Ginkgo biloba is ineffective for improving cognitive function in people with MS. The guidelines also state that there is weak evidence that Ginkgo biloba is possibly effective for reducing fatigue.

What Does the Research Show?

• The 2014 evidence-based guidelines from the American Academy of Neurology, which were reaffirmed in February 2023, concluded that Ginkgo biloba is ineffective for improving cognitive function in people with MS, but that it is possibly effective over 4 weeks for reducing fatigue in MS. These conclusions are based on four small studies.
• A 2012 randomized controlled trial involving 120 participants with MS with some cognitive impairment found that Ginkgo biloba twice a day for 12 weeks did not improve cognitive performance.
• A 2013 Cochrane review of four randomized controlled trials evaluated pharmacologic treatments, including Ginkgo biloba, for memory disorder in MS. The reviewers concluded that based on available evidence, there is no convincing evidence to support the use of Ginkgo biloba as an effective treatment for memory disorder in MS patients.

Safety

• Side effects of ginkgo may include headache, nausea, gastrointestinal upset, diarrhea, dizziness, or allergic skin reactions. More severe allergic reactions have occasionally been reported.
• There are some data from animal models to suggest that ginkgo can have an effect on the pharmacokinetics of several drugs; however, current available clinical evidence suggests that low doses do not pose a risk for clinically relevant herb-drug interactions.
• Fresh ginkgo seeds contain large amounts of ginkgotoxin, which can cause serious adverse reactions, including seizures and death. Roasted seeds can also be toxic. Products made from standardized ginkgo leaf extracts contain little ginkgotoxin and appear to be safe when used orally and appropriately.
• National Toxicology Program (NTP) studies showed that rats and mice developed tumors after being given a specific ginkgo extract for up to 2 years. Further studies are needed to find out what substances in ginkgo caused the tumors and whether taking ginkgo as a dietary supplement affects the risk of cancer in people.

Omega-3 Fatty Acid Supplementation

Although some studies on omega-3 fatty acid supplementation have shown some beneficial effects on relapse rates, inflammation, and improving quality of life, currently there is insufficient evidence to assess any real beneficial effects of omega-3 fatty acid supplementation on MS.

Evidence-based guidelines from the American Academy of Neurology, which were issued in 2014 and reaffirmed in February 2023, concluded that a low-fat diet with fish oil supplementation is probably ineffective for reducing MS-related relapse, disability, or magnetic resonance imaging (MRI) lesions, or for improving fatigue or quality of life.

What Does the Research Show?

• The 2014 evidence-based guidelines from the American Academy of Neurology concluded that, based on three reviewed studies, a low-fat diet with fish oil supplementation is probably ineffective for reducing MS-related relapse, disability, or MRI lesions, or for improving fatigue or quality of life.
• A 2020 Cochrane review of 30 trials examining dietary interventions, including polyunsaturated fatty acids (PUFAs) and dietary plans with recommendations for specific whole foods, macronutrients, and natural health products, concluded that PUFA administration may not differ when compared to alternatives with regards to relapse rate, disability worsening, or overall clinical status in people with MS; however, evidence is uncertain.

Safety

• Omega-3 fatty acid supplements usually do not have negative side effects. When side effects do occur, they typically consist of minor gastrointestinal symptoms.

Vitamin D

To date, results of studies have been conflicting as to whether vitamin D may provide a therapeutic benefit for people with MS. A 2018 Cochrane review found very low-quality evidence suggesting no benefit of vitamin D for patient-important outcomes among people with MS. 

What Does the Research Show?

• A 2024 systematic review and meta-analysis of 9 studies involving 867 participants found that vitamin D supplementation had no significant impact on clinical outcomes in people with MS.
• A 2018 Cochrane review of 12 randomized controlled trials involving a total of 933 participants with MS found very low-quality evidence suggesting no benefit of vitamin D for patient-important outcomes. The reviewers concluded that vitamin D appears to have no effect on recurrence of relapse, worsening of disability, and MRI lesions. Effects on health-related quality of life and fatigue were unclear.
• Results of a large, 5-year randomized trial in 468 participants with MS suggest that low blood levels of vitamin D may be a risk factor for long-term disease activity and progression. Moreover, higher levels of serum levels of 25-hydroxyvitamin D (25[OH]D), a marker of vitamin D status, were associated with lower degree of MS activity, MRI lesion load, brain atrophy, and clinical progression during the 5 years of follow-up. More controlled studies, however, are needed to determine if further supplementation of already adequate vitamin D levels is therapeutic in any way that may affect disease course and progression.

Safety

• Limited intervention studies in MS suggest that vitamin D supplements are generally well tolerated in MS.
• High doses may cause fatigue, abdominal cramps, nausea, vomiting, renal damage, and other adverse effects.