Multiple sclerosis (MS) is a disease that affects the central nervous system (CNS), which includes the brain, spinal cord and optic nerves. MS involves an abnormal response of the body’s immune system, which is directed against the person’s own CNS. The immune system targets myelin, a substance that surrounds and insulates nerves. Damaged myelin then forms scars (sclerosis), giving the disease its name, and these scars are thought to be responsible for most of the wide-ranging symptoms that people with MS experience. Various FDA-approved medications can help reduce the frequency of MS relapses, slow progression of disability from MS, and relieve symptoms of MS, but none of these medications are completely effective. Many people continue to experience relapses, progression, and symptoms from their MS. It is now becoming more common for some people to use cannabis (marijuana) to try to alleviate their MS symptoms. Although people have used cannabis for thousands of years, systematic study of the compounds in cannabis as therapeutic treatment has only occurred in about the last 20 years. MS is a type of autoimmune disease that attacks the central nervous system (CNS), which includes the spine, the brain, the eyes, and their respective nerves. The inflammation associated with MS can damage myelin (the insulation that surrounds the nerves) and the actual nerves. This causes scarring in multiple damaged areas, lending to the name multiple sclerosis. Sclerosis is another term for hardening or scarring of tissue.
This damage disrupts information being sent to and from the brain through the nerves and leads to a wide variety of symptoms. Symptoms typically include difficulty walking, spasticity (i.e. stiffness or involuntary muscle spasms – typically in the legs), muscle weakness or numbness, tiredness, pain, cognitive problems, bladder and bowel issues, and changes in mood. These symptoms can be different for every patient and may change as time goes on.
MS is one of the more researched diseases regarding its relationship to CBD due to the drug approved in the EU, Sativex. This is the same drug as Nabiximols in the U.S. and is currently an investigational product seeking FDA-approval. Sativex is a mouth spray that contains THC and CBD in a 1:1 ratio. It is indicated for treatment of moderate to severe spasticity associated with MS in those who have not responded well to other anti-spasmodic medications.
A lot of the data is valid and supports the use of CBD (with THC) in MS, especially regarding the symptom of spasticity. There is other data to help support its use with MS patients who also have pain or overactive bladder. For CBD alone, there is preclinical data to support CBD helping to decrease the immune system attacking itself and to reduce inflammation.
In 1998, an article was published in the Proceedings of the National Academy of Sciences that discussed how the cannabinoids CBD and THC are antioxidants and neuroprotective. The authors suggested that because of their antioxidant properties, they would have therapeutic uses as neuroprotective agents, making them ideal candidates for drug targets for certain diseases.
Due to this revolutionary report, the U.S. government issued a patent on “Cannabinoids as antioxidants and neuroprotectants”. The patent states:
The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and HIV dementia. Non-psychoactive cannabinoids, such as cannabidiol, are particularly advantageous to use because they avoid toxicity that is encountered with psychoactive cannabinoids at high doses useful in the method of the present invention.
Currently, this patent is still active. However, it will soon be expiring. The expiration date is April 21st, 2019 which is great news for all of the CBD research teams. This U.S. government patent has likely prevented many investigators from pursuing this research avenue for CBD. If they are not able to market CBD as a neuroprotectant and make money to pay for the trials they put on, then what is the point of doing it? There has not been an incentive for them to do research in this area, but now it seems that there might be.
Therefore, this patent expiration could mean more clinically relevant studies being performed about CBD and neuroplasticity, as it relates to its neuroprotective and antioxidant qualities. This also could mean that they may come up with a drug product, like Epidiolex which is indicated for rare childhood seizures, for a neurodegenerative disease in the somewhat near future.
Cannabis-based treatment induces polarity-reversing plasticity assessed by theta burst stimulation in humans.
This 2009 study looked at the effects of Sativex, which contains both THC and CBD, on synaptic (the area of the cells where two nerve cells join together) plasticity in humans with multiple sclerosis (aka MS).
They found that the endocannabinoid system does play a role in synaptic plasticity. Specifically, they looked at the motor cortex of the brain, which is the part of the brain that affects movement. Since their study population was made up of MS patients, this makes sense because they have motor coordination problems as part of their disease. Also, Sativex is indicated for symptoms of MS in the EU.
Of note, this study did not solely look at the effects of CBD.
Evidence supporting the use of cannabis to treat symptoms of MS Cannabis has been studied for many uses in many different conditions. This section focuses on the evidence about cannabis to treat symptoms commonly experienced by people with MS. This is not a comprehensive review of all studies that have been conducted, but highlights the largest and highest quality studies. Spasticity Spasticity that causes muscle spasms and stiffness is common in people with MS – over 85% of people with MS have some spasticity, 50% have at least mild spasticity, and up to 17% have severe spasticity. [14] Although several medications can be used to treat spasticity, they may not be completely effective and their use or dose may be limited by side effects. The CAMS (Cannabinoids in MS) study is the largest randomized control trial to date to examine the effectiveness of cannabis on MS symptoms. [15] In this study, 630 people with MS from 33 centers in the United Kingdom were assigned to receive dronabinol, cannador or placebo twice daily for 15 weeks. Although there was no significant difference between groups in changes in the physician-administered test of spasticity, those taking either of the cannabis products (dronabinol or cannador) reported significantly greater improvements in spasticity, spasms, and sleep compared to those taking placebo. There were no significant changes in tremor or bladder symptoms in any of the groups. At the end of the study, participants could elect to continue taking their assigned study medication and were followed for another 12 months. [16] At that time, they found that those taking dronabinol had a small improvement on the physician-administered test of spasticity, the Ashworth scale, but this was not seen in the Cannador or placebo group, and no other measures were administered. The explanation for these findings is unclear.
The MUSEC trial (MS and Extract of Cannabis) in 2012 also examined patients’ perceptions of changes in muscle stiffness. [17] In this study, 279 people with MS took either Cannador or placebo for 12 weeks. People taking cannabis extract had almost twice as much relief from muscle stiffness as those taking placebo at both 4 and 8 weeks, and they also had improvements in spasms and sleep. Studies have also looked at the effect of nabiximols on spasticity. In two similar studies, one study with 160 people and another with 189 people, the groups using nabiximols had statistically significantly greater improvement in self-reported spasticity compared to those using placebo [18,19], but there were no significant improvements in other symptoms, including pain or urinary symptoms. [18] Next, a study with 337 patients found that nabiximols improved self-reported spasticity more than placebo, and that the response in the first four weeks tended to predict the ongoing response for the entire 15-week study. [20] Finally, a two-part study in 2011 looked at the effects of nabiximols on patient-rated spasticity. [21] First, 572 people with MS-related spasticity that was not relieved by medications were treated with either nabiximols or placebo for 4 weeks. Those in the nabiximols group who had at least a 20% reduction in spasticity went on to the second part of the study. This group of 241 individuals was assigned to use either nabiximols or placebo for 12 weeks. The group taking nabiximols had significantly improved self-reported spasticity. Overall, as of a 2015 systematic review, there have been 11 randomized studies with a total of 2138 patients comparing the effect cannabinoids of any type with placebo on spasticity related to MS. Although the specific details of the studies vary, most studies suggest that cannabinoids are associated with improvements in self-reported spasticity, but the improvements in objectively measured spasticity generally do not reach statistical significance [22].
MS-Related Pain
Before we get into how CBD oil interacts within our system and the possible uses of CBD oil for pain, we must first discuss what happens organically within our system. It’s called the endocannabinoid system (ECS). The ECS is a biological system composed of endocannabinoids, which are human made lipid-based regressive neurotransmitters that bind to cannabinoid receptors. In simpler terms, endocannabinoids are just the cannabinoids that our body naturally produces. The ECS is also made up of cannabinoid receptor proteins that are expressed throughout the vertebrate of the central nervous system (including the brain) and the peripheral nervous system. The ECS is involved in regulating a variety of physiological and cognitive processes including appetite, pain sensation, mood, memory, and in mediating the pharmacological effects of cannabis. It is also involved in creating some of the physiological and cognitive effects of physical exercise in humans. The ECS is what gives people a “runner’s high” when working out.
Cannabinoids ingested from plants influence our body’s ECS which means they can affect the functions that are listed above. The reason why marijuana causes a euphoria is because the THC binds to the cannabinoid receptors in the brain. CBD, however, barely touches these receptors at all and manages to affect the system through other pathways in addition to the cannabinoid receptor pathways.
For chronic pain use, there have been more studies on both animals and humans that show great promise in the management of chronic pain. One major review was conducted on studies of hemp oil from the late 1980s to 2007. It stated the average conclusion from these studies was that CBD oil seemed to be effective in overall pain management without any major side effects. It was also concluded from this review that hemp oil had some potential in treating insomnia related to chronic pain. A more recent study from 2012 also concluded that CBD oil can potentially reduce pain and inflammation, supporting the other studies. From this study, it was also stated that the subjects were not likely to build up a tolerance to the effects of CBD oil. This means that, unlike opioids where tolerance is a major issue and people must take more and more to get the same effect (leading to toxicities and overdoses), the dose for CBD oil can be maintained without ramping it up.
Knowing that CBD oil potentially requires no increasing dosage as time goes on, it is no wonder why this could prove beneficial in treating various types of pain, including neuropathic pain. Current treatment options for neuropathic pain are very limited, have moderate efficacy, and have dose-limiting side effects. A review of multiple studies ranging from the history of CBD oil, to pharmacologic development and even clinical trials results, showcased the benefits of using CBD for neuropathic pain. Another study that focused on neuropathic pain developed from the autoimmune disease multiple sclerosis (aka MS) concluded that CBD oil can potentially help treat neuropathic pain in patients with multiple sclerosis. More studies for neuropathic pain need to be done.
As you can see, pain is a complex phenomenon involving many different chemicals, neurotransmitters, and receptors. Pain is a common symptom of MS, affecting around two-thirds of people with MS. People with MS can experience many different types of pain, including headache (43%), nerve pain in their arms or legs (26%), back pain (20%), painful spasms (15%) and trigeminal neuralgia (3.8%). [23] Most pain experienced by people with MS is central neuropathic pain (pain caused from damage to the central nervous system) or pain from spasms. The role of cannabis in pain relief is complex and not well understood. Some evidence suggests that the CB1 receptors in the brain and peripheral nerves play a role in modulating and processing pain. [24] Cannabis may also decrease pain by decreasing inflammation. [25] Several studies have looked at the effect of cannabis on neuropathic pain in people with MS. One study lasting four weeks in 64 people with MS found a 41% decrease in mean pain intensity in the group taking nabiximols compared to a 22% decrease in pain in the group taking the placebo. [26] Similar effects on pain were found in two additional studies, one with 630 people and the other with 279 people, comparing the effects of oral cannabinoids (cannador or dronabinol), with placebo. [15,17] In addition, a recent small study with 15 people with MS with neuropathic pain found that adding nabilone to gabapentin was effective and well-tolerated for MS-related neuropathic pain. [27]
Fewer studies have examined the effectiveness of inhaled cannabis on pain and none of these have been carried out in people with MS. Two studies comparing the effectiveness of inhaled cannabis with placebo for neuropathic pain due to peripheral neuropathy or other neurologic conditions found that neuropathic pain was reduced more in the group using inhaled cannabis when compared to the placebo group. [28,29] A 2011 systematic review of randomized controlled trials performed before 2010 examined the effects of cannabinoids of any type (smoked cannabis, oral extracts, nabilone, synthetic THC, nabiximols) on chronic non-cancer pain (including but not limited to pain from MS). In 15 of the 18 studies, the cannabinoids provided at least modest pain relief. [30] A 2015 update by the same authors that evaluated 11 additional studies performed between 2010 and 2014 found that 7 of these 11 studies also showed that cannabinoids were more effective than placebo. [31]
Research
The medical use of cannabis remains controversial. In addition to the legal status of the drug, the limited research evidence remains a major barrier to our understanding of the potential benefits and risks of cannabis use in people with MS. The last two decades have seen an increase in the amount of scientific research in this area. However, case report, and anecdotes still greatly outnumber high-quality studies. High quality scientific methods and standards like those used to study conventional medications need to be applied to the study of cannabis to fully understand its potential for medical use. Clinical trials researching cannabis are limited in part because cannabis research is difficult. In the USA, researchers must file an Investigational New Drug (IND) application with the FDA, obtain a Schedule I license from the US Drug Enforcement Administration (DEA), and obtain cannabis for the study. When botanical or smoked cannabis is investigated, it must come from the same plot grown by the FDA, leaving unexplored other strains and hybrids that patients may encounter. These obstacles can make conducting these studies more time-consuming and challenging than other investigations. There is also the question of how widely the results of these studies can be applied since some studies examine liquid extracts, others use the single molecule preparations, others use smoked cannabis. Despite the restrictions and limitations, scientific research on cannabis and cannabinoids continues to grow. Also, more and more people are showing interest in using cannabis to treat their MS symptoms. It is therefore important for people with MS and their providers to understand the available evidence and to work together to make the choices that are right for them. For specific questions about cannabis and your health, do not hesitate to contact your health-care provider.
It is important to keep in mind that, as with most topics surrounding CBD, most of this research is pre-clinical or anecdotal evidence due to it being performed in animal models or small groups of humans. This means that it is not definitive by any means but is hypothesis-generating. It allows for more specific research to be conducted and eventually clinical trials to be completed.
Multiple Sclerosis
A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex(®) ), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis.
This randomized, double-blind, placebo-controlled 2011 trial was done in patients with MS who had not responded to other anti-spasmodic medications. They were given Sativex in addition to other spasticity medications.
The researchers used a Numeric Rating Scale (NRS) to measure the severity of spasticity in the patients. They found that the there was a significant difference in this score between the groups, with lower scores in the group receiving Sativex.
From this, the authors concluded that Sativex (in addition to other medications) was effective at reducing spasticity in MS patients. Of note, this study did not look at CBD by itself, but in combination with THC.
A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis.
This randomized, double-blind, placebo-controlled 2013 trial was done in patients with MS who did not have adequate responses to pain medications. They were given Sativex in addition to other pain medications.
The primary endpoint of this study was not significant. They compared responsiveness of medication in the Sativex group and the placebo group and found them to be similar. However, in the next phase of their trial they found that people had failed treatment faster in the placebo group than in the Sativex groups. They also found that the Sativex group had lower pain scores and higher sleep quality scores.
These results make sense because traditional pain medications are effective at reducing pain when first given, however patients begin to develop tolerance to them, and they start to not work as well for their pain. So, this supports the idea that Sativex could be a better option for chronic pain due to the time to treatment failure being longer in that group. Of note, this study did not look at CBD by itself, but in combination with THC.
Randomized controlled trial of Sativex to treat detrusor overactivity in multiple sclerosis.
This randomized, double-blind, placebo-controlled 2010 trial was done in patients with MS who also had overactive bladder (OAB). They were given Sativex in addition to other bladder medications.
Their primary endpoint, reduction in daily number of urinary incontinence episodes, was not significant. However, other symptoms such as nocturia (waking up and needing to urinate at night) and number of voids per day were significant in favor of Sativex.
The authors concluded that although their primary endpoint was not significant, Sativex did have a positive impact on the symptoms associated with OAB and may provide some use for bladder dysfunction in MS patients. Of note, this study did not look at CBD by itself, but in combination with THC.
Purified Cannabidiol, the main non-psychotropic component of Cannabis sativa, alone, counteracts neuronal apoptosis in experimental multiple sclerosis.
This 2015 study was performed in mice and sought out to see if CBD could help with MS-induced apoptosis (self-killing of cells).
They found that CBD did impact mediators involved with apoptosis. They also found that there was not formation of apoptotic bodies in the spine.
From this, the authors concluded that this provides a different mechanism behind how CBD alone can help with MS through its “anti-apoptotic power”.
Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: a role for A2A receptors.
This 2013 study utilized a viral model of MS to determine if CBD can protect against the harmful effects of inflammation associated with this disease.
They found that CBD decreased pro-inflammatory mediators and decreased the number of other harmful mediators involved with inflammation. They also found that the A2A adenosine receptor was involved in the anti-inflammation mechanism.
The authors concluded that CBD has anti-inflammatory effects that can have significant potential in treating MS.
The research surrounding CBD and MS is different than other research regarding CBD. It has more data in humans, and clinical trials that are the golden standard of randomized, double-blind, and placebo controlled. With this, the data supporting the use of CBD and MS is valid and can be used more confidently to give suggestions regarding MS. Therefore, currently professional judgement can be used when deciding if the data is “good” or not, and that varies from person to person based on their diverse experiences.
It is always best practice to talk with a health care professional before using CBD to help with any health conditions you may have. They can help you evaluate the research and decide if it is the best option for you. They can also help you determine if any drug interactions exist with any current medications you might be taking and give suggestions for how to avoid them.
