Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review
Cannabis therapy has been considered an effective treatment for spasticity, although clinical reports of symptom reduction in multiple sclerosis (MS) describe mixed outcomes. Recently introduced therapies of combined Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD) extracts have potential for symptom relief with the possibility of reducing intoxication and other side effects. Although several past reviews have suggested that cannabinoid therapy provides a therapeutic benefit for symptoms of MS, none have presented a methodical investigation of newer cannabinoid treatments in MS-related spasticity. The purpose of the present review was to systematically evaluate the effectiveness of combined THC and CBD extracts on MS-related spasticity in order to increase understanding of the treatment’s potential effectiveness, safety and limitations.
We reviewed MEDLINE/PubMed, Ovid, and CENTRAL electronic databases for relevant studies using randomized controlled trials. Studies were included only if a combination of THC and CBD extracts was used, and if pre- and post-treatment assessments of spasticity were reported.
Six studies were systematically reviewed for treatment dosage and duration, objective and subjective measures of spasticity, and reports of adverse events. Although there was variation in the outcome measures reported in these studies, a trend of reduced spasticity in treated patients was noted. Adverse events were reported in each study, however combined TCH and CBD extracts were generally considered to be well-tolerated.
We found evidence that combined THC and CBD extracts may provide therapeutic benefit for MS spasticity symptoms. Although some objective measures of spasticity noted improvement trends, there were no changes found to be significant in post-treatment assessments. However, subjective assessment of symptom relief did often show significant improvement post-treatment. Differences in assessment measures, reports of adverse events, and dosage levels are discussed.
Spasticity, an involuntary increase in muscle tone or rapid muscle contractions, is one of the more common and distressing symptoms of multiple sclerosis (MS). Medicinal treatment may reduce spasticity, but may also be ineffective, difficult to obtain, or associated with intolerable side effects [1, 2]. Cannabis, a psychotropic drug known for its analgesic properties, also has a long history as an effective and tolerable treatment for spasticity [3, 4]. Demographic evidence has shown that many people with MS use cannabis for symptom management .
Clinical studies, animal models, and anecdotal reports [6–8] have suggested that cannabis may be an effective treatment of MS spasticity. The antispastic effect of cannabis has been supported through a demonstration of the inhibitory properties in exogenous agonists for cannabis receptors found in the CNS . Early clinical trials reporting the efficacy and safety of cannabis use in MS have focused on the effects of Δ 9 -tetrahydrocannabinol (THC). Although these clinical studies reported a therapeutic benefit for MS symptoms, there were concerns of potential intoxication and other side effects of cannabis-based treatment . Another clinical study using a cannabidiol (CBD) extract documented a reduction in spasticity-related pain but not in spasticity .
More recent combination therapies using whole plant extracts of both THC and CBD have been introduced and there is evidence that CBD, which is not psychotropic, may reduce THC levels in the brain and attenuate its psychotropic side effects [11–14]. Such therapies may potentially provide a tolerable yet effective treatment for MS symptoms . A number of recent studies [15–22] have investigated the potential efficacy and safety of whole plant extracts of THC and CBD. One of the first large-scale studies of cannabis treatment for MS-related spasticity compared whole plant cannabis extracts with THC and a placebo, and found mixed evidence for the therapeutic benefit of spasticity in MS. A recent review  that included a number of these recent studies provided additional support for the benefit of cannabinoids in MS-related spasticity but called for further study into long-term treatment and side effects. A systematic evaluation of recent research had not previously been conducted, and was needed in order to provide organized evidence of cannabinoid treatments and direction for future clinical studies. We therefore systematically reviewed studies that used a combination extract of THC and CBD for the treatment of spasticity.
We conducted a comprehensive search using MEDLINE/PubMed, Ovid, and CENTRAL (Cochrane Central Register of Controlled Trials) for English-language only literature published from 1999 to April 2009 using different combinations of the following MeSH and free text terms: cannabis, cannabinoid, THC, CBD, multiple sclerosis, spasticity, spasms. Reference lists from retrieved reports were reviewed for additional studies. Unpublished data were not sought and abstracts, letters, case reports, and review articles were excluded. (See Additional file 1 for a Quality of Reporting of Meta-analyses (QUOROM) statement checklist.)
Selection and quality assessment
Only randomized, placebo-controlled, human studies of shorter treatment periods (under 6 months) were included. Studies were evaluated for methodological quality using Jadad scores  and only studies with Jadad scores of 4 or higher were considered for inclusion. Relevant trials included those that had administered a combination THC and CBD extract, those in which clinically stable spasticity had been established prior to trial and those that reported objective measures of pre- and post-treatment spasticity. Studies that used active control groups were not excluded. Abstracts were reviewed for relevancy and full text versions of potentially relevant randomized controlled studies were reviewed. Reports not considered relevant were excluded and all included reports were read in entirety.
Data were extracted independently by the authors and any disagreements were resolved by consensus. The following information was extracted from each report: study type, study objective, sample size, controls, type and amount of cannabinoid used, treatment duration, objective and subjective outcome measures, and reported adverse events.
A qualitative summary of the data was completed to compare the various outcome measures used across the included studies. In addition, a quantitative analysis of the one common outcome measure (Ashworth scale) used by the included studies was performed in order to assess statistical heterogeneity.
Flow of included studies
Electronic searches found 38 studies that were potentially relevant to the present review. Of these, 33 did not meet the inclusion/exclusion criteria, including 27 reports that were not randomized, controlled trials. One study was excluded for focusing on spasticity-related pain and two were excluded for not assessing the effects of a combined extract of THC and CBD. Two studies were excluded for reporting long-term follow-up data (see Figure 1).
Flow diagram of included studies.
Six double-blind, randomized, placebo-controlled trials published between 2002 and 2007 were analyzed [15–20]. These studies included a total of 481 patients with MS who were administered a combined extract of both THC and CBD. Three trials used a crossover design. Three trials used a parallel design in which 339 patients were administered a placebo only. Trial periods ranged from 2 to 15 weeks. Objective spasticity measures were extracted when included in the assessment data from at least two studies. All six trials reported an adjusted mean change score in the Ashworth scale assessment. Other measures of spasticity included mean changes from a baseline score in the following assessments: Visual Analogue Scale (VAS), a rating scale to measure the severity of spasticity; walk time; Rivermead Mobility Index (RMI), a measure of disability related to mobility; and self-reported ratings of spasm frequency or severity. (See Table 1 for the specific characteristics of each reviewed study.)
Table 1 Analysis of six randomized controlled trials reporting measures of spasticity after THC-CBD treatment
Overall reduction of spasticity
Five studies [16–20] concluded that cannabis extract may decrease spasticity and improve mobility in patients with MS. One study  reported no reduction in spasticity. Adverse effects were reported in each study; however side effects from combined extracts of THC and CBD were generally well-tolerated. Two blinded studies comparing combined extracts of THC and CBD to extracts of THC alone found a lower incidence of adverse events in the combined THC and CBD trials [16, 17], and one study found a higher incidence of adverse events . In all three comparison studies, there was no distinction in efficacy between THC extracts and combined THC and CBD extracts.
In one study , 50 patients were assessed with the Ashworth scale for muscle tone and showed significant improvement during the active treatment trial. The other five studies reported little to no improvement in their versions of the Ashworth scale. It should be noted that the Ashworth scale is subject to individual assessor evaluation and there may have been variation between studies in the modification of scale measures.
Visual Analogue Scale
Three studies reported data from VAS scores [15, 17, 19]. Two studies reported that patients on active treatment showed a significant improvement in VAS scores [17, 19], and one reported no significant difference . In one study , daily recorded assessment data from 14 MS patients were mixed with data from six patients with other neurological disorders. The other studies recorded daily  or weekly  assessments.
Although five studies included walk time in their proposed assessments, only two studies [16, 19] reported data from 160 patients with MS. Although both showed a trend for improvement in walk time, P-value did not reach statistical significance in one study  and was not reported in the other .
Rivermead Mobility Index
Three studies [16–18] reported RMI scores for 275 MS patients. Although there was a trend for improvement from baseline to study completion, mean changes in assessment were significant in one study  and insignificant in the other two studies.
Other subjective rating scales
All six studies reported an additional measure of subjective assessment. Rating scales were completed by a total of 379 patients in order to record various changes in spasticity throughout the trials. Five studies [16–20] reported significant improvements in spasticity as subjectively rated by patients with MS and one reported deterioration .
Three of the studies [15, 19, 20] did not report adequate (mean and standard deviation) Ashworth scale data for inclusion in the quantitative meta-analysis. This left three studies for the calculation of the pooled mean difference in Ashworth scores. The chi-square test for heterogeneity showed evidence of significant variation between the three studies (χ 2 = 5.25, P = .07, l 2 = 62%). Given that only three of the six studies reported adequate Ashworth scale data [16–18], of these three only one demonstrated statistically significant findings , and the high level of heterogeneity, a quantitative analysis of the data was deemed inappropriate.
There were some limitations to the systematic review. First, this review did not include unpublished data. There may be ongoing clinical trials of combination THC and CBD therapy as it is a relatively recent therapy. There is also the possibility that other clinical reports using whole plant cannabis extracts may have been appropriate for review, but were not included without report of specific methodology. A meta-analytical review of the effects of cannabis on spasticity would be useful, but was not deemed appropriate for the present review because of the variation in assessment data.
Subjective vs. objective measures
The validity of the Ashworth scale as an outcome measure has been previously questioned . However, we have shown that other objective measures of spasticity (i.e. RMI, walk time) may also fail to adequately support the improvements found in scores from more subjective measures (i.e. rating scales, diary entries). A long-term follow-up study  showed a significant improvement in the Ashworth scale, however, the change was still small and was found in the THC group only. Another concern is that participants of both active and placebo trials may not be entirely blind to their treatment status , and this may affect subjective assessments. It remains that, without a validated, objective measure of spasticity, it will be difficult to accurately measure the effects of cannabis therapy on MS spasticity.
Adverse effects were reported in each trial in which patients received active treatment (including THC-only treatment). There is some evidence that combined extracts of THC and CBD may attenuate side effects of THC alone, and future studies are needed to compare the safety of combined cannabis extracts with traditional treatment. Dosage is another concern that should be considered in the context of side effects. Incidence of side effects varies greatly depending on the amount of cannabis needed to effectively limit spasticity. In one study , it was noted that the initially permitted dosage level sometimes resulted in marked side effects, and the dosage was thereafter reduced. The careful monitoring of symptom relief and side effects is critical in reaching an individual’s optimal dose. Finally, it should be noted that several adverse events were also reported in each trial in which patients received a placebo. In a long-term follow-up  of one of the reviewed studies , it was determined that most of the reported adverse events were unrelated to cannabis treatment. Considering the distress and limitations spasticity brings to individuals with MS, it would be important to carefully weigh the potential for side effects with the potential for symptom relief, especially in view of the relief reported in subjective assessment.
We found evidence that combined extracts of THC and CBD may reduce symptoms of spasticity in patients with MS. Although the subjective experience of symptom reduction was generally found to be significant, objective measures of spasticity failed to provide significant changes. In a previous study of spasticity-related pain, MS patients also reported a subjective perception of symptom reduction with cannabinoids . However, since at least one past animal study has provided objective, physiological evidence for the antispastic properties of cannabinoids , the distinction between perceived symptom relief and objective physiological changes in humans should therefore be primary in future research efforts.
Given that adverse events occurred in each reviewed trial, we also encourage future comparison studies of cannabis treatments at a wide range of dosage in order to balance potential side effects with maximum therapeutic benefit.
Finally, there is evidence that cannabinoids may provide neuroprotective and anti-inflammatory benefits in MS. Neuroinflammation, found in autoimmune diseases such as MS, has been shown to be reduced by cannabinoids through the regulation of cytokine levels in microglial cells . The therapeutic potential of cannabinoids in MS is therefore comprehensive and should be given considerable attention.
What Are the Benefits of CBD for Multiple Sclerosis?
Research on CBD for MS is limited, but shows it might reduce pain and spasticity
Kelly Burch is a freelance journalist who has covered health topics for more than 10 years. Her writing has appeared in The Washington Post, The Chicago Tribune, and more.
Verywell Health articles are reviewed by board-certified physicians and healthcare professionals. These medical reviewers confirm the content is thorough and accurate, reflecting the latest evidence-based research. Content is reviewed before publication and upon substantial updates. Learn more.
Emily Dashiell, ND, is a licensed naturopathic doctor who has worked in group and private practice settings over the last 15 years. She is in private practice in Santa Monica, California.
Multiple sclerosis (MS) is an autoimmune disease that causes a range of symptoms, including fatigue, cognitive impairment, and muscle weakness. MS can manifest in many ways, but patients have one thing in common: the symptoms of MS have a big impact on their quality of life.
To manage symptoms, some MS patients turn to cannabidiol, or CBD, a non-psychoactive compound found in the cannabis plant. Scientists are still researching the benefits of CBD for people with MS, but early indications show that CBD might help control some MS symptoms, such as pain and muscle stiffness.
This article will review what you should know about CBD and multiple sclerosis, including the potential benefits, safety concerns, and optimal dosage.
Verywell / Michela Buttignol
Immune System and Multiple Sclerosis
Multiple sclerosis is an autoimmune disease. That means that the symptoms of the disease occur because the immune system is attacking healthy cells in the way that it’s supposed to attack viruses and other pathogens.
In MS, the immune system targets the myelin sheath, a protective coating that wraps around nerve cells in the spinal cord and brain. When the immune system attacks this barrier, it causes inflammation and damage, which can impair the nerve signaling that facilitates movement, breathing, thinking, and more.
The severity of MS symptoms varies, depending on the location of the attack and the extent of the damage to the myelin sheath, but they most often include fatigue, muscle weakness or stiffness, and cognitive dysfunction.
Cannabinoids and the Immune System
Cannabinoids are a group of compounds found in the cannabis plant. The two main cannabinoids are THC (the psychoactive ingredients in marijuana) and CBD (which does not have a psychoactive component).
The body processes cannabinoids via cannabinoid receptors, which are found in the brain and in immune cells. This is all part of the endocannabinoid system, which regulates inflammation, immune function, motor control, pain, and other bodily functions commonly affected by MS.
This connection helps explain why CBD can be beneficial for MS. Cannabinoids have been shown to reduce inflammation and regulate immune response. CBD does this without mind-altering properties, making it appealing to people looking for relief from MS symptoms without the “high” of marijuana.
Benefits of CBD for MS
In a recent meta-analysis, researchers concluded that cannabinoids, including CBD, are “probably effective” at alleviating certain symptoms of MS, including pain and abnormal muscle tightness (spasticity), but “probably not effective” for treating muscle tremors or incontinence.
Additional research supported using CBD for MS. Here are some key findings:
- A 2018 scientific review found that CBD supplementation reduced pain, fatigue, inflammation, depression, and spasticity in people with MS, while improving mobility. The authors concluded that recommending CBD supplementation for people with MS would be advisable.
- A 2014 scientific review found that Sativex (nabiximols), a CBD nasal spray, can help reduce pain, spasticity, and frequent urination in patients with MS.
- Two different 2021 medical reviews found that in animal models, CBD helps regulate the immune system, reducing the autoimmune response that causes MS symptoms. More research is needed, but in the future this may mean that cannabis-derived medications and CBD could be used to treat the progression of MS, not just the symptoms.
Are There Any Side Effects?
CBD is generally considered safe, and it does not have mind-altering properties. A dose of up to 300 mg daily of CBD is safe for up to six months. Higher doses are safe for a shorter amount of time.
However, like any other supplements or medication, CBD may have side effects in some individuals. These may include:
- Low blood pressure
- Damage to the liver
In addition, CBD may interact with many other prescription drugs. It’s best to speak with your healthcare provider before supplementing with CBD, especially if you are pregnant or breastfeeding. Most doctors who treat MS are familiar with CBD, since at least 20% of MS patients are currently using CBD.
CBD is legal for consumption in the United States, but cannabis products that contain THC are illegal at the federal level. Be sure to understand the legal and professional implications of using CBD, especially if you are regularly screened for drug use.
Keep in mind that the Food and Drug Administration does not oversee or regulate any CBD supplements, so it’s important to purchase CBD products from a reputable source.
How to Use CBD for MS
CBD is available in many different forms, including topicals, tinctures, edibles, and nasal sprays.
You’ll also have to decide whether you want to take a full or broad-spectrum CBD, which contains other cannabinoids, or a CBD isolate, which contains just cannabidiol. Limited research suggests there may be a benefit to the “entourage effect”: It’s believed that having other cannabinoids present may make CBD more effective.
Consulting your healthcare provider can help you decide where to start with CBD supplementation. They can offer insight as to what has worked for other patients and guide you toward an appropriate dose of CBD.
How to Buy CBD for MS
It’s important to deal with reputable dispensaries when purchasing CBD for MS. Here’s what you should consider when buying CBD to treat MS:
- The legal status of CBD in your state, including whether you need a medical cannabis card
- The possible impact of taking CBD on your professional licenses or other areas in your life
- Your goals in taking CBD, and the symptoms you would most like to address
- Whether you would like a CBD isolate or a full-spectrum product that contains other cannabinoids
- Whether the retailer is licensed in your state
- Where the product was sourced (grown)
- Whether the product has a COA, or certificate of analysis, which shows the chemical composition of a substance
A Word from Verywell
MS can have a huge impact on your quality of life, which is why so many people look for relief from MS symptoms. The research around CBD and MS is very promising: It shows that some people experience reduced pain and spasticity when they use CBD supplements.
In the future, CBD-derived medication may even be used to control the progression of the disease by reducing inflammation.
Unfortunately, use of CBD for MS is still in its infancy, and there’s a clear need for more research. For now, it’s best to talk with your doctor and trusted peers when deciding whether CBD is right for you. Don’t be shy about speaking up: Research has shown that up to 60% of MS patients are currently using cannabis and 90% would consider it.
You shouldn’t feel any shame or hesitation about investigating this treatment option. However, it’s important to understand any legal and professional implications for where you live, especially if you use a product containing THC.
Although there is a lot of promise for CBD to treat MS, there is no FDA-approved treatment. Using it in combination with more traditional medically sanctioned treatment is likely a good course of action.
Frequently Asked Questions
Research indicates that CBD likely helps with muscle spasticity in people with MS. A UK-based study found that physicians did not measure a large improvement in spasticity in people taking CBD versus a supplement. However, the people taking CBD reported a reduction in spasticity compared with those taking a placebo. Because of that, the Multiple Sclerosis Society says that CBD is likely effective for spasticity.
CBD is generally considered safe, and some research shows that it likely helps treat pain and spasticity caused by MS. However, CBD is not FDA approved for treating MS or its symptoms. You should speak with your healthcare provider about using CBD to treat MS.
Much of the research on using CBD for MS pain has been done using oral supplements and nasal sprays. Some people also report benefits from smoking CBD flowers or cannabis. It’s best to speak with your healthcare provider and consider the legal standing of CBD and cannabis in your state as you decide how best to use CBD to treat MS pain.