Cannabidiol to Improve Mobility in People with Multiple Sclerosis
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Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that affects an estimated 2.3 million people worldwide (1). The symptoms of MS are highly varied but frequently include pain, muscle spasticity, fatigue, inflammation, and depression. These symptoms often lead to reduced physical activity, negatively impact functional mobility, and have a detrimental impact on patients’ quality of life. Although recent years have seen significant advances in disease modifying therapy, none of the current treatments halts or cures MS related symptoms (2). As a consequence, many people with MS (PwMS) look for alternative and complementary therapies such as cannabis.
The cannabis plant contains many biologically active chemicals, including ~60 cannabinoids (3). Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are typically the most concentrated chemical components of cannabis and believed to primarily drive therapeutic benefit. There is evidence that CBD has a number of beneficial pharmacological effects (4, 5). It is anti-inflammatory, antioxidative, antiemetic, antipsychotic, and neuroprotective. The review of 132 original studies by Bergamaschi et al. (6) describes the safety profile of CBD by highlighting that catalepsy is not induced and physiological parameters (heart rate, blood pressure, and body temperature) are not altered. Moreover, psychomotor and psychological functions are not negatively affected. High doses of up to 1,500 mg per day and chronic use have been repeatedly shown to be well tolerated by humans (6). Additionally, there is also evidence that CBD may reduce the negative psychotropic effects, memory impairment, and appetite stimulation, anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions (7, 8).
Currently, many PwMS utilize cannabis to manage a variety of symptoms. Kindred et al. (9) showed in a web-based survey, which was hosted by the National Multiple Sclerosis Society that 66% of PwMS currently use cannabis for symptom treatment. Furthermore, a study from Canada found that approximately 50% of PwMS would consider the usage of cannabis if the legal status is clear and scientific evidence is available (10). Cannabis is legal in twenty-nine states for the use of specific medical conditions—including MS. Sixteen more states have passed laws that explicitly allow the medical use of CBD. It is suggested that recent increases in the social acceptance of CBD will lead to increases in the number of PwMS using cannabis to treat their symptoms. Anecdotal reports indicate that an increasing number of PwMS use cannabis (medical marijuana) as a supplement to improve their mobility.
Based on the following considerations, it is our opinion that CBD supplementation maybe advisable for PwMS to reduce fatigue, pain, spasticity, and ultimately improve mobility. An overview of the potential impacts of CBD on mobility of PWMS is show in Figure Figure1 1 .
Impacts of CBD on mobility.
Cannabidiol Reduces Spasticity, Pain, Inflammation, Fatigue, and Depression in PwMS
Despite the common use of and interest in cannabis by people with MS (PwMS), there is very limited empirical data pertaining to its impact on physical mobility. The benefits related to cannabis use in PwMS are still under investigation. However, data indicates that cannabis, with 1:1 or greater CBD:THC ratio, reduces muscle spasticity (11) and pain in PwMS (12). The American Academy of Neurology (13) has highlighted cannabis’ safety profile as well as these benefits. However, there are currently no studies, which investigated the effects of cannabis on mobility in PwMS, some studies have suggested that cannabinoids may exert positive effects on health by decreasing inflammation and decreasing pain (6). Furthermore, inflammation plays an important role in the generation of MS related fatigue (14). Specifically, chronic peripheral inflammation and a resulting overactivity of the vagus nerve are related to fatigue in PwMS (14). There is indirect evidence that reductions in spasticity, pain, and fatigue may result in improvements in the mobility of PwMS (15–17). Furthermore, it is suggested that CBD showed a dose-dependent antidepressant-like effect in the animal model (18). The exact mechanism underlying such activity is still unknown. Depression is an important contributory factor to the observed impaired mobility in PwMS (15). Based on extant evidence we propose that the impact of cannabidiol (CBD) on mobility to be investigated.
Cannabis Reduces the Usage of Prescription Drugs, Particularly Pharmaceutical Opiods, Benzodiazepines, and Antidepressants
These medications continue to be widely prescribed in the majority of PwMS suffering from pain, spasticity, anxiety, and panic disorders. Common side effects of opioid administration include physical dependence, dizziness, sedation, nausea, vomiting, tolerance, constipation, and respiratory depression. Physical dependence and addiction are clinical concerns that may prevent accurate prescribing and in turn insufficient pain management. Traditional benzodiazepines are associated with sleep disturbances and anterograde amnesia. Another concern with long duration benzodiazepines such as diazepam or flurazepam, is drowsiness and “hangover effect.” Antidepressants can cause a wide range of unpleasant side effects, including nausea, fatigue and drowsiness, blurred vision, dizziness, and anxiety. It is obvious that those drugs delay or even prevent successful physical rehabilitation. A recent epidemiological study by Piper et al. (19) showed that among people that frequently used opioids, over three-quarters (77%) indicated that they reduced their use since they started cannabis. Approximately two-thirds of patients decreased their use of antianxiety (72%), migraine (67%), and sleep (65%) drugs following medical cannabis which significantly exceeded the reduction in antidepressants or alcohol use. Complete or part replacement of these drugs by specific cannabis products should definitely be the long-term goal.
However, objections to the notion that cannabinoids should be used to improve the mobility in PwMS include the following: (1) limited scientific evidence for the effectiveness of cannabis on mobility in PwMS; (2) uncertainty of legal status; (3) social stigmatization from friends, family, and authorities such as employers, landlords, and law enforcement; (4) incidence of dependency; and (5) negative psychoactive effects of cannabis. These objections have some merit and should be taken into consideration. It is important to note that the psychoactive effects of cannabis, such as cognitive impairments, psychosis, and anxiety are due to tetrahydrocannabinol (THC). However, CBD has antipsychotic properties and can also counter several negative side effects of THC. Most PwMS prefer to avoid feeling high. Therefore, individuals should seek out strains of cannabis containing equal or higher levels of CBD, compared to THC. Another concern is the risk of addiction. It is estimated that ~9% of individuals utilizing cannabis will become dependent on the drug (20). Although a significant risk, this incidence of dependency is significantly lower than that of approved chronic pain management pharmaceuticals (21). Observing for cannabis dependency is suggested for all patients.
Things to Consider
Serious drug interactions have not been seen with CBD in combination with any other drugs.
However, CBD and other plant cannabinoids can potentially interact with many pharmaceuticals. For example, the activity of liver enzymes such as cytochrome P450 is impacted. More than 60 percent of marketed pharmaceuticals are metabolized by this group of enzymes. At high enough dosages, CBD will temporarily deactivate these liver enzymes, thereby altering how a wide range of compounds is metabolized. The exact mechanisms are unknown and more human studies, which monitor CBD-drug interactions are needed (22). PwMS who are taking any prescription medications are strongly advised to consult with a medical professional.
Labeling Accuracy of CBD Extracts
A major concern is the often labeling accuracy of CBD extracts. Bonn-Miller et al. (23) found a wide range of CBD concentrations among CBD products purchased online. The tested products contain 26% less CBD than labeled, which could negate any potential clinical benefit. The over labeling of CBD products and that THC was detected (up to 6.43 mg/mL) in 18 of the 84 samples tested suggest that there is a need for federal and state regulatory agencies to take steps to ensure label accuracy of CBD products sold online and in dispensaries.
Can a Cannabidiol User Test Positive for Marijuana?
In the CBD products without THC, then a urine test would not yield a positive result for THC metabolites. However, most CBD products contain minimal amounts of THC in CBD. An important aspect in cannabinoid compounds is the entourage effect. The entourage effect means that the compounds in cannabis work more sufficient together than if the compounds are isolated. Therefore, CBD products may contain more cannabis compounds, including THC, to increase the effectiveness of the product (7). Furthermore, often a study by Merrick et al. (24) is cited which showed that CBD could be converted into THC after prolonged exposure to “simulated” gastric acid. However, there is no scientific evidence that this reaction occurs in vivo in humans (25). If someone is using a CBD product and needs to undergo urine drug tests, lab reports should be requested and examined to ensure that the CBD product contain exactly what is expecting and on the label.
It is clear that more research is needed. However, because of the safety of CBD and if the concerns listed above are accounted, we are in the opinion that we already have some good reasons to believe that CBD enriched cannabis is useful to improve the mobility of PwMS.
TR and JS contributed to drafting the article and revising it critically for important intellectual content. All the authors approved the final version of the manuscript.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
1. Browne P, Chandraratna D, Angood C, Tremlett H, Baker C, Taylor BV, et al. Atlas of multiple sclerosis 2013: a growing global problem with widespread inequity . Neurology (2014) 83 :1022–4.10.1212/WNL.0000000000000768 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
2. Ziemssen T, Derfuss T, de Stefano N, Giovanonni G, Palavra F, Tomic D, et al. Optimizing treatment success in multiple sclerosis . J Neurol (2016) 263 :1053–65.10.1007/s00415-015-7986-y [PMC free article] [PubMed] [CrossRef] [Google Scholar]
3. Ebert T, Zolotov Y, Eliav S, Ginzburg O, Shapira I, Magnezi R. Assessment of Israeli physicians’ knowledge, experience and attitudes towards medical Cannabis: a Pilot Study . Isr Med Assoc J (2015) 17 :437–41. [PubMed] [Google Scholar]
4. Mannucci C, Navarra M, Calapai F, Spagnolo EV, Busardo FP, Cas RD, et al. Neurological aspects of medical use of cannabidiol . CNS Neurol Disord Drug Targets (2017) 16 ( 5 ):542–53.10.2174/1871527316666170413114210 [PubMed] [CrossRef] [Google Scholar]
5. Russo EB. Cannabidiol claims and misconceptions . Trends Pharmacol Sci (2017) 38 :198–201.10.1016/j.tips.2016.12.004 [PubMed] [CrossRef] [Google Scholar]
6. Bergamaschi MM, Queiroz RH, Zuardi AW, Crippa JA. Safety and side effects of cannabidiol, a cannabis sativa constituent . Curr Drug Saf (2011) 6 :237–49.10.2174/157488611798280924 [PubMed] [CrossRef] [Google Scholar]
7. Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid–terpenoid entourage effects . Br J Pharmacol (2011) 163 :1344–64.10.1111/j.1476-5381.2011.01238.x [PMC free article] [PubMed] [CrossRef] [Google Scholar]
8. Niesink RJ, van Laar MW. Does cannabidiol protect against adverse psychological effects of THC? Front Psychiatry (2013) 4 :130.10.3389/fpsyt.2013.00130 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
9. Kindred JH, Li K, Ketelhut NB, Proessl F, Fling BW, Honce JM, et al. Cannabis use in people with Parkinson’s disease and multiple sclerosis: a web based investigation . Complement Ther Med (2017) 33 :99–104.10.1016/j.ctim.2017.07.002 [PubMed] [CrossRef] [Google Scholar]
10. Banwell E, Pavisian B, Lee L, Feinstein A. Attitudes to cannabis and patterns of use among Canadians with multiple sclerosis . Mult Scler Relat Disord (2016) 10 :123–6.10.1016/j.msard.2016.09.008 [PubMed] [CrossRef] [Google Scholar]
11. Wade DT, Makela P, Robson P, House H, Bateman C. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients . Mult Scler (2004) 10 :343–441.10.1191/1352458504ms1082oa [PubMed] [CrossRef] [Google Scholar]
12. Rog DJ, Nurmikko TJ, Friede T, Young CA. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis . Neurology (2005) 27 :812–9.10.1212/01.wnl.0000176753.45410.8b [PubMed] [CrossRef] [Google Scholar]
13. Koppel BS, Brust JCM, Fife T, Bronstein J, Youssof S, Gronseth G, et al. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders . Neurology (2014) 82 :1556–63.10.1212/WNL.0000000000000363 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
14. Sander C, Hildebrandt H, Schlake HP, Eling P, Hanken K. Subjective cognitive fatigue and autonomic abnormalities in multiple sclerosis patients . Front Neurol (2017) 8 :475.10.3389/fneur.2017.00475 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
15. Zwibel HL. Contribution to impaired mobility and general symptoms to the burden of multiple sclerosis . Adv Ther (2009) 26 ( 12 ):1043–57.10.1007/s12325-009-0082-x [PubMed] [CrossRef] [Google Scholar]
16. Berthoux F, Bennett S. Introduction: enhancing mobility in multiple sclerosis . Int J MS Care (2011) 13 ( 1 ):1–3.10.7224/1537-2073-13.1.1 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
17. Sumowski JF, Leavitt VM. Body temperature is elevated and linked to fatigue in relapsing-remitting multiple sclerosis, even without heat exposure . Arch Phys Med Rehabil (2014) 95 :1298–302.10.1016/j.apmr.2014.02.004 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
18. El-Alfy A, Ivey K, Robinson K, Ahmed S, Radwan M, Slade D, et al. Antidepressant-like effect Δ9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L . Pharmacol Biochem Behav (2010) 95 :434–42.10.1016/j.pbb.2010.03.004 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
19. Piper BJ, DeKeuster RM, Beals ML, Cobb CM, Burchman CA, Perkinson L, et al. Substitution of medical cannabis for pharmaceutical agents for pain, anxiety, and sleep . J Psychopharmacol (2017) 31 ( 5 ):569–75.10.1177/0269881117699616 [PubMed] [CrossRef] [Google Scholar]
20. Lopez-Quintero C, Pérez de los Cobos J, Hasin DS, Okuda M, Wang S, Grant BF, et al. Probability and predictors of transition from first use to dependence on nicotine, alcohol, cannabis, and cocaine: results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) . Drug Alcohol Depend (2011) 115 ( 1–2 ):120–30.10.1016/j.drugalcdep.2010.11.004 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
21. Hood SD, Norman A, Hince DA, Melichar JK, Hulse GK. Benzodiazepine dependence and its treatment with low dose flumazenil . Br J Clin Pharmacol (2014) 77 ( 2 ):285–94.10.1111/bcp.12023 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
22. Iffland K, Grotenhermen F. An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies . Cannabis Cannabinoid Res (2017) 2 :139–54.10.1089/can.2016.0034 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
23. Bonn-Miller MO, Loflin MJE, Thomas BF, Marcu JP, Hyke T, Vandrey R. Labeling accuracy of cannabidiol extracts sold online . JAMA (2017) 7 :1708–9.10.1001/jama.2017.11909 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
24. Merrick J, Lane B, Sebree T, Yaksh T, O’Neill C, Bnks SL. Identification of psychoactive degradents of cannabidiol in simulated gastric and physiological fluid . Cannabis Cannabinoid Res (2016) 1 :102–12.10.1089/can.2015.0004 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
25. Grotenhermen F, Russo E, Zuardi AW. Even high doses of oral cannabidol do not cause THC-like effects in humans . Cannabis Cannabinoid Res (2017) 2 :1–4.10.1089/can.2016.0036 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
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.
How CBD Reduces Multiple Sclerosis Symptoms Has Now Been Revealed
Multiple Sclerosis (MS) is a chronic, sometimes debilitating, autoimmune disease which affects the brain and spinal cord. Symptoms, and the severity of those symptoms, can vary dramatically over time with many sufferers reporting symptoms worsening steadily over time, or going through periods of relapse and remission where symptoms come and go.
The disease is most commonly characterized by issues with mobility, ranging anywhere from numbness in one or more limbs, to paralysis. People with MS also report experiencing one, or a combination of, the following symptoms: problems with their vision, pain or muscle spasms, cognitive impairment, and fatigue.
Though it is still unknown exactly causes MS, studies on animals with experimental autoimmune encephalomyelitis (EAE), the animal model for MS in humans, revealed antigen-specific T cells crossing the blood-brain barrier which triggered neuroinflammation. This led to the destruction of myelinated neuronal cells and produced symptoms of paralysis as a result of this demyelination.
CBD oil and MS
Cannabidiol (CBD), the main non-psychoactive component of cannabis, is known to exhibit both anti-inflammatory and neuroprotective effects against known and suspected autoimmune diseases, such as ulcerative colitis and Alzheimer’s disease. Given what little is known about the etiology of MS, it was theorized that medicinal CBD could also be of benefit to MS patients. Drugs such as Sativex, a cannabis oil consisting mainly of CBD and Δ9-tetrahydrocannabinol (THC), can now be prescribed to MS patients living in countries and states with medicinal cannabis programs who feel that their symptoms are not being relieved by traditional pharmaceuticals.
While clinical studies show that patients receiving Sativex do report a better quality of life and lower spasticity than they did prior to starting CBD oil treatment, the exact method through which CBD interacts with the mechanisms that are thought to cause MS remains unclear.
New research from the Department of Pathology in the University of South Carolina School of Medicine, Columbia, published last week in Frontiers in Immunology studied the treatment of murine EAE with CBD oil in order to characterize the previously unknown biochemical mechanisms through which CBD inhibits MS-like symptoms.
CBD and multiple sclerosis
The research team induced EAE in groups of female mice using the peptide MOG35-55 as an antigen. These mice were then treated with either CBD or a control vehicle once the first EAE symptoms were observed. The progression of disease was tracked using clinical scores associated with different symptom expressions. The scores were measured on a scale of 0 to 6, representing the full range of observable symptoms from no clinical signs all the way to death. The mean score for each group of mice was calculated daily and the scores for CBD treated mice (EAE-CBD) and the control group treated with the vehicle (EAE-VEH) were compared to assess the objective effectiveness of CBD treatment.
The EAE-VEH mice developed EAE at a steady rate, with a maximum mean clinical score of 4.1 over the course of the study. A clinical score of 4 in this study corresponds to a state of tetraparalysis. The EAE-CBD mice experienced a slower onset of symptoms, and at their peak the mean clinical score of symptoms was 2.2, which indicates only partial paralysis of the hind limbs.
With confirmation that CBD treatment does have a clear effect on EAE, the researchers carried out a number of in vivo and ex vivo tests to try to pinpoint exactly what biochemical mechanisms were responsible for the effectiveness of the treatment.
Marijuana and MS
It is already known that EAE in mice is triggered by Th1 and TH17 cells, so the researchers first chose to examine the effect of CBD on the cytokines that affect these cells, as well as some additional cytokines and transcription factors that are closely related.
It was found that EAE-VEH mice had considerably higher levels of the transcription factors T-bet and RORγT compared to mice who did not have EAE. These levels were not seen in EAE-CBD mice, indicating that treatment with CBD may affect these transcription factors.
Analysis of the cytokine levels in EAE-VEH mice re-stimulated with MOG showed heightened levels of IFNγ, IL-17, TNFα, and IL-10 cytokines. By comparison, the EAE-CBD mice displayed far lower levels of IFNγ and IL-17, but had a similar TNFα reading, and production of IL-10 in the mice had increased.
Taking into account both the differences in cytokine and transcription factors, the data indicates that CBD treatment leads to the suppression of cytokines and transcription factors that are known to display pro-inflammatory effects, while also promoting the production of IL10, a cytokine which is known to have strong anti-inflammatory properties.
The importance of MDSCs
MDSCs, or myeloid-derived suppressor cells, are another suspected factor in the onset of MS and MS-like symptoms as they are known to take part in the suppression of neuroinflammation. It is thought that MDSCs also play a role in autoimmune diseases by affecting T cell function and so the effect of CBD on MDSCs was also studied as an alternate route by which CBD might be suppressing MS symptoms.
EAE-CBD mice were found to show dramatically higher counts of CD11b+Gr-1+ MDSCs than the EAE-VEH mice in the peritoneal cavity where the CBD was injected, but that these levels were not heightened in the central nervous system, spinal cord, or brain. Levels in the central nervous system were actually slightly reduced in comparison to EAE-VEH mice. It is theorized that this difference is due to the MDSCs in the periphery being unable to migrate to the central nervous system, but by inhibiting T cell induction in secondary lymphoid organs it was possible for the CBD-induced MDSCs to prevent the T cells from proliferating and causing the clinical disease. This was supported by the total viable cell number of the T cells, which showed that the MDSCs were not killing the T cells after they were triggered by the autoimmune disease, but that they were being suppressed and inhibited from proliferating.
Importantly, MDSCs are known to produce IL-10. Researchers noted a dose-dependent response from CBD treatment on MDSC levels in this study, indicating that CBD’s ability to mediate EAE symptoms could be a result of both its direct IL-10 induction, and by an indirect effect through raising the MDSC levels which in turn produces more of the anti-inflammatory IL-10.
An additional experiment was carried out to investigate the effects of MDSC depletion on clinical symptoms. Lowering MDSC levels by injection of the antibody RB6-8C5 into mice that had been successfully treated with CBD reversed the effects of the treatment. This further supports the theory that indirect manipulation of MDSCs is a significant contributing factor to the effectiveness of CBD treatment.
The new model for CBD’s action on MS symptoms
The research carried out in this study has identified two previously unknown mechanisms through which CBD can act to curb the clinical effects of MS and MS-like conditions – the first being through a direct positive influence on the levels of anti-inflammatory cytokines and a similar negative influence on pro-inflammatory cytokines; the second being via an indirect manipulation of anti-inflammatory MDSCs which inhibit the T cell induction that normally occurs in autoimmune disease. The discovery of these mechanisms provides the field of cannabis science with a better understanding of the action of CBD in the body, which is important in the efforts to discover more effective drugs to combat autoimmune diseases.
The authors of the study conclude their research paper with the recommendation that “CBD may constitute an excellent candidate for the treatment of MS and other autoimmune diseases” as a novel non-psychoactive therapeutic. Further study of MDSC manipulation by cannabinoid-based drugs could lead to the development of novel drugs and other future advances in autoimmune disease treatment.
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