Fibromyalgia is poorly understood and as a result the development of treatment has been challenging. Treatments are often not effective and patients go from one therapy to another, accumulating disappointments and side effects. Unfortunately, people living with fibromyalgia often have adverse reactions to medication further limited treatment options.
There is increasing interest in medical cannabis as a treatment for fibromyalgia. Cannabis has been used to treat cramps and pain as far back as 5,000 years ago in ancient China. This is not just due to its effects on pain (analgesic properties) but also due to its potential to help with other associated symptoms such as insomnia, anxiety and depression.
The Endocannabinoid System
Cannabis contains over 500 active compounds including at least 140 cannabinoids—the number has been gradually growing in the past few years due to new research—that can affect the body by interacting with and activating the endocannabinoid system (ECS). The ECS is divided into three main parts: receptors that are distributed throughout the body, cannabinoid molecules that combine with and activate the receptors and metabolic enzymes. There are particularly high concentrations of cannabinoid receptors found in the nervous system, immune system, bones and joints, which is where the ECS has its main functions. The central role of the enzymes is to synthesize the molecules that activate the ECS or to break them down and stop them activating the receptors.
Cannabinoid molecules that activate the ECS can be found in three different environments: within the body, in the cannabis plant, and in pharmaceutical preparation.
When naturally-occuring in the body they are called endocannabinoids (“endo” means inside in Greek) and play an important role in the bodies “homeostasis,” or balance. Endocannabinoids are produced by the body in reaction to different types of stress including physical and psychological. The exact functions of the ECS are still in the process of being understood.
The other naturally-occurring cannabinoids are present in the plant Cannabis sativa and are known as phytocannabinoids. The most-studied phytocannabinoid molecules are tetrahydrocannabinol (THC) and cannabidiol (CBD). These phytocannabinoids have similarities to the endocannabinoids in their ability to activate the ECS.
Finally cannabinoids have also been synthesized as pharmaceutical preparations. Most of the pharmaceutical preparations are synthesized cannabinoid molecules that are analogues of (similar or almost identical to) THC, for example Nabilone, which has been approved by the FDA for use in the United States.
There have been two cannabinoid receptors identified to date, and it’s likely that more receptors will be identified through future research. Both cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) can be activated by combining with cannabinoid molecules—whether endocannabinoids, phytocannabinoids or synthetic cannabinoids. The combination of the cannabinoid molecules and the cannabinoid receptor activates specific signalling pathways within cells. One of the central results of these signalling pathways in cells is to decrease neurotransmitter release. Neurotransmitters are the primarily signals of the nervous system, which are involved in many processes including pain perception and other brain functions such as sleep and anxiety. CB1 receptors are mainly located in the nervous system in both the brain and peripheral nerves that extend from the spinal cord. CB2 receptors, on the other hand, have been found mainly located on cells of the immune system and different types of musculoskeletal cells. It is these effects on pain and sleep and anxiety that may be helpful in fibromyalgia.
Fibromyalgia & Cannabis
Research into medical cannabis is relatively new, mainly due to its legal status—it’s impossible or at least very difficult to perform medical studies on illicit substances. Since regulations have changed there is increasing interest and an increasing number of trials being performed. However, this area of research is still relatively young and therefore there is still not a lot of data regarding the effects of cannabis in fibromyalgia.
A well designed study published by Pain Medicine in October 2020 looked at how high-THC cannabis oil could affect the symptoms and quality of life of fibromyalgia patients. The study looked at 17 women with fibromyalgia in the city of Florianopolis, Brazil, who were given one drop of THC a day, which was increased according to their symptoms.
The subjects were given a Fibromyalgia Impact Questionnaire (FIQ) to fill out on several occasions over the eight week study, and researchers found that “the cannabis group presented a significant decrease in FIQ score in comparison with the placebo group.” Namely, they found that the cannabis group reported significant improvements in the following measurement: “feel good,” “pain,” “do work,” and “fatigue.”
A recent high quality but very small study (randomized placebo-controlled trial) examined the analgesic (pain control) effect of pharmaceutical grade cannabis in 20 patients with fibromyalgia. The four groups received either cannabis high in THC content with minimal CBD, equal THC and CBD, high CBD with minimal THC or placebo (no THC or CBD). After treatment patients measured spontaneous pain levels (meaning pain that is present without any obvious trigger) and underwent pain tests (pain that as elicited by a trigger). Patients receiving the combination of CBD and THC had statistically improved pain scores in the induced pressure pain test—30% decreased pain score compared to placebo. None of the treatments had an effect on spontaneous pain levels. CBD without THC cannabis did not demonstrate any effects of pain levels.
Two other randomized controlled trials looked at the effect of the synthetic cannabinoid Nabilone on fibromyalgia. One trial compared treatment with Nabilone to placebo and the other trial compared Nabilone to Amitriptyline (a tricyclic antidepressant used in fibromyalgia). The trial comparing Nabilone to placebo provided low-quality evidence that the cannabinoid provided improvement in pain control and measure of quality of life. No effect on fatigue or depression was seen. The study that examined Nabilone vs Amitriptyline found low quality evidence of improved sleep with cannabinoid treatment. In contrast to the previous trial there was no effect on pain or quality of life.
A larger observational trial of 367 patients was recently published examining plant-based medical cannabis that may have been either THC or CBD rich. Eighty percent of patients reported an improvement in their symptoms such as sleep and depression. There were also significant improvements in pain and quality of life. In terms of side effects, the most frequent were dizziness (8%), dry mouth (7%), nausea & vomiting (5%) and hyperactivity (5%). Hallucinations was reported in 1% of the participating patients. The results of this trial seem very encouraging; nonetheless it is important to recognize that this is an observation trial. That means in terms of the methodology there are many issues where the results may have been affected by factors other than the treatment.
Regarding the side effects of cannabinoid treatment: the most significant include immediate effects on motor and cognitive function that may last up to 5 hours. Additionally, smoking cannabis may be a risk factor for developing respiratory disease. Cannabis use has also been associated with psychosis, paranoia and anxiety especially related to THC.
So far, the current research demonstrates low- to medium-quality evidence that treatment with cannabinoids, either plant based or synthetic, have a beneficial effect on people living with fibromyalgia. The strongest evidence is that this effect is produced by THC in contrast to limited evidence of the effectiveness of CBD in fibromyalgia. Clinical research into treatment with cannabinoids is relatively new and the majority of the described trials are small. It is likely that with larger high-quality trials the effects of cannabinoid treatment in fibromyalgia will become clearer.
There are known associations between fibromyalgia, migraines and irritable bowel syndrome (IBS). It has been suggested that these diseases/syndromes share a similar underlying cause and that they may all be treated with cannabis. The proposed cause is endocannabinoid deficiency. There is some research that has found decreased endocannabinoid levels in patients with migraines and decreased levels in a study of mouse models with pain hypersensitivity. There is also increasing data showing that the ECS may play a role in the development of altered gastrointestinal function. However, currently there are no studies examining endocannabinoid levels in fibromyalgia or IBS. Thus endocannabinoid deficiency is still a theory, there is little data and it is an area of ongoing research.
Fibromyalgia is a debilitating disease with limited treatment. Medical cannabis may provide a new treatment option. Despite limited data the research increasingly seems to demonstrate beneficial effects. The decision to start treatment should be taken with the treating physician having been discussed and considered the pros and cons.
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