Cannabis, marijuana, and CBD oil for fibromyalgia and other pain conditions

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In this video, we will look at what cannabis, marijuana, and CBD oil are and the effects on fibromyalgia and other chronic pain conditions.  


My name is Andreas Persson and I am a physiotherapist and specialist in pain and pain rehabilitation.


Cannabis also called hemp or marijuana is a plant that has many uses. Different genetic variants of cannabis have been cultivated for different purposes. Varieties of cannabis and different parts of the plant are used in the treatment of various medical conditions, for recreational use and to make clothes, paper, rope, supplements, and food.(1) 


Scientists have found more than 140 pharmacologically active substances in cannabis.(2) In connection to the isolation and study of the substances, receptors, and molecules in the body that they affect have been discovered. The receptors that are influenced by the substances in cannabis and the body’s own substances that affect the same receptors, as well as the effects that occur as a result of the activation are called the endocannabinoid system.(1)


The system is believed to be relatively inactive most of the time but is activated under certain circumstances such as high nerve cell activity during stress, anxiety, and pain. When the system is activated, it has a calming effect in the central nervous system, which provides relaxation, reduced anxiety, and possibly also reduced pain. In the body, the activated system leads to reduced metabolism.(3) 


Important parts of the endocannabinoid system are cannabinoid receptors 1 and 2 often called CB 1 and CB 2. CB 1 is found in both the brain and in the body, while CB 2 is mainly found in the immune system. The endocannabinoid system is of course not created for smoking marijuana. The system has its own neurotransmitters that are released when the system is being activated. Two proprietary neurotransmitters that act in the system are anandamide and 2-arachidonylglycerol.(1) 


These neurotransmitters are called endocannabinoids while the substances that come from the cannabis plant and have their effect in the same system are called phytocannabinoids.(1) 


The reason why the phytocannabinoids affect the endocannabinoid system is that they are similar to the body’s own neurotransmitters, which among other things means that they can bind to the same receptors.(1) 


The two best-known phytocannabinoids are tetrahydrocannabinol which is abbreviated THC and cannabidiol which is abbreviated CBD.(1) 


THC is the substance that makes you high when you smoke cannabis. THC has an inhibitory effect on the release of neurotransmitters by different neurons thru binding to the CB-1 receptor on the presynaptic neurons.(1) 


Cannabidiol works by other mechanisms such as increasing the activity of serotonin receptors and by increasing the levels of the body’s own cannabinoids.(1) 


Some varieties of the cannabis plant have been cultivated to contain as much THC as possible. The leaves and flowers are dried and can be smoked. Extracts with a high content of THC can also be extracted and consumed in other ways such as thru drinking or eating. These products usually also contain CBD and other phytocannabinoids.(1) 


Other varieties of the cannabis plant are grown so that the leaves and flowers contain as little THC and as much cannabidiol and other phytocannabinoids as possible. From these variants, CBD oil and other oils with different combinations of phytocannabinoids are extracted. Oils with many different phytocannabinoids are sometimes called full-spectrum oils.(1) 


These products have no intoxicating effect because they contain such a low content of THC, which means that in the US and also in Europe they are classified differently than the products that contain more THC. This means that they may be sold according to specific rules and that they are legal in certain areas, where cannabis products with a higher THC content are not.(1) 


Seeds from the cannabis plant are extracted and processed into seed oil. This oil contains no THC and very little CBD. However, it contains omega 3, omega 6, other fatty acids, and antioxidants which are used in supplements.(1) 


What are the effects of cannabis substances on the body?


The endocannabinoid system is complicated. Although the system generally has an inhibitory effect on nerve cells, it both inhibits nerve cells that stimulate other nerve cells and nerve cells that inhibit other nerve cells. (4) This means that various substances that are added to the body by for example smoking marijuana or consuming CBD oil can both inhibit and stimulate various parts of the nervous system as well as other cells and organs in the body.(3) And even though the researchers know a lot about how the substances affect the body, they know far from everything. What we will look at are just a few selected effects of cannabis that may be relevant to people with chronic pain.


As I have mentioned in previous videos, there is a descending pain modulating system in the brain stem. Here we see a pain signal coming in from the body because an apple fell on Åke’s arm.

Here we have an abstract variant of the pain system with the pain signal that travels up to the brain.


The descending pain modulating system can both amplify and inhibit the upward going pain signals.(5)


There are plenty of CB-1 receptors in the descending pain modulating system. (4) CB-1 receptors are the receptors that can be activated by THC. This makes it likely that intake of THC may in some way affect pain through the descending system.


There are also CB-1 receptors in the system that make you feel full and satisfied when eating a meal. Increased activity in the system with more neurotransmitters (either the bodies own or added from the outside as THC) stimulates the CB-1 receptors and causes you to eat more and gain weight.(3)


A synthetic variant of THC called Dronabinol is in fact used as a medicine to make people with HIV / AIDS, or anorexia, gain weight.(6) 


Unlike THC, CBD can increase the activity of serotonin receptors and also affect the body’s own cannabinoids, which in turn can also affect the immune system. However, CBD has no effect on the CB1 receptors, which means that they have no intoxicating effect and neither any of the other effects caused by stimulation of the CB-1 receptors.(1)


So these are examples of some specific effects that different phytocannabinoids have. But the important thing is not what specific effects the substances have at the molecular level, but what effects they have on pain, well-being, and health in fibromyalgia and other pain conditions. And the most reliable way to get knowledge about it is to look at the scientific studies that have been done.


Effects of various cannabis products on fibromyalgia and other long-term pain conditions


According to a review of scientific studies by Amnon and colleagues published in 2020, no randomized controlled trials have been conducted to test the effect of substances from the Cannabis Plant on patients with fibromyalgia..(2)

Randomized controlled trials, also called RCT studies, mean that participants have been randomized into one of two or more groups, where participants in the different groups receive different treatments. The different groups are then compared to see if the effect of the different treatments differs. This is the gold standard for scientific studies and it usually takes several fairly large RCT studies with similar results to be able to say whether a treatment works or not.


Two small RCT studies have been done with a drug called Nabilone. Nabilone is a chemically developed substance to resemble THC and its effect. The first study showed a significant reduction in pain and anxiety as well as an overall reduction in the impact of fibromyalgia on life in the treatment group. The second study did not show a difference in these factors but improved sleep quality in those with fibromyalgia with sleep problems when compared with those who received an antidepressant drug..(2)


There are some other studies with other designs that do not have as high evidential value.


In an observational study with 102 people with fibromyalgia who received cannabis oil with 6% or 22% THC, 44% had better sleep quality and 33% of the participants experienced a reduced impact of fibromyalgia on life. It is important to point out that this means that 56% did not get better sleep quality and 67% did not get a reduced impact of fibromyalgia on life..(2)


In a study from Israel with 367 participants with fibromyalgia who used cannabis, the median pain value for those who continued the study after six months had decreased from 9 to 5 on a scale from 0-10 where 0 was no pain and 10 was the worst possible pain..(2)


It is important to point out that the participants in all the studies mentioned have received the substance THC or drugs with a similar effects. Very few studies appear to have been performed in people with fibromyalgia with CBD products containing little or no THC..(2)


In a study comparing inhalation of THC and CBD in people with fibromyalgia, it was only in those who received THC that it was possible to see pain relief 3 hours after ingestion..(2)


What is the evidence for Cannabis in other pain conditions?


In a review of RCT studies and also observational studies that tested cannabinoids for the treatment of all types of chronic pain conditions except those caused by cancer, it was concluded that there was no good evidence that the substances reduce the pain and the other related symptoms, except in neuropathic pain, that is, pain due to nerve damage, where there was some evidence of pain relief.(7) 

A systematic review and meta-analysis of RCT studies in all types of pain from 2017 show that there is some evidence that cannabis helps with neuropathic pain. There was a statistically significant difference in favor of cannabis treatment compared to placebo overall also for other chronic pain conditions, but the effect size was not considered large enough to make any real difference. It was even the case that the effect on pain after surgery was the opposite. It turned out that a placebo was more effective than cannabis, which suggests that cannabis may instead have increased the pain.(8)


What are the side effects?


But what about the side effects of different cannabis products. In a study with Cannabidiol, that is CBD, in people with epilepsy, drowsiness, decreased appetite, and diarrhea occurred in 36% of the participants.(1) Another article also mentions sleep disorders and elevated liver enzymes as side effects of cannabidiol.(2)


Reported side effects that have occurred with short-term use of cannabis with a high content of THC are impaired short-term memory, altered judgment, psychosis, and paranoia.(2)


With long-term use, the following side effects have been reported: addiction, altered brain development, chronic bronchitis, chronic psychosis, and schizophrenia.(2)


In contrast, in a study that followed people with chronic pain who used cannabis for a year, the participants showed no more side effects than the control group.(2)


In a study where two groups of experts on drugs and addiction assessed how dangerous and addictive different drugs were, it could be seen that cannabis was judged to be less dangerous and less addictive than both alcohol and tobacco.(9) Such information makes me question why cannabis is illegal in many places while alcohol and tobacco are not.


Summary

In summary, there are many different cannabis products. Some are used as supplements, for food, and in other products such as clothes and ropes and some have a pharmacological effect when consumed.


Among those that have a pharmacological effect, some contain THC the compound which makes people high, and some do not contain THC.


In addition to THC, many other phytocannabinoids affect the body’s cannabinoid system. Cannabidiol or CBD is the most well-known and researched of them.


There is no good evidence that CBD reduces the symptoms of fibromyalgia or other pain conditions.


There is some evidence that cannabis products with THC can reduce pain and other symptoms of fibromyalgia and several other pain conditions.


The pain condition for which there is the best evidence for pain relief is neuropathic pain

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References

1. Harrison JVD, Bauer BA, Mauck KF. Clinicians’ Guide to Cannabidiol and Hemp Oils. Mayo Clin Proc. 2019;94(9):1840-51. 

2. Berger AA, Keefe J, Winnick A, Gilbert E, Eskander JP, Yazdi C, et al. Cannabis and cannabidiol (CBD) for the treatment of fibromyalgia. Best Pract Res Clin Anaesthesiol. 2020; 34(3):617-31. 

3. Woods SC. The Endocannabinoid System: Mechanisms Behind Metabolic Homeostasis and Imbalance. Am J Med. 2007;120(2 Suppler 1):9-17. 

4. Bouchet CA, Ingram SL. Cannabinoids in the descending pain modulatory circuit: Role in inflammation. Pharmacol Ther. 2020;209:107495. 

5. Lockwood S, Dickenson AH. What goes up must come down: insights from studies on descending controls acting on spinal pain processing. J Neural Transm (Vienna). 2020;127(4):541-9. 

6. Badowski ME, Yanful PK. Dronabinol oral solution in the management of anorexia and weight loss in AIDS and cancer. Ther Clin Risk Manag. 2018;14:643-51. 

7. Stockings E, Campbell G, Hall WD, Nielsen S, Zagic D, Rahman R. Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions: a systematic review and meta-analysis of controlled and observational studies. Pain. 2018;159(10):1932-54. 

8. Aviram J, Samuelly-Leichtag G. Efficacy of Cannabis-Based Medicines for PainManagement: A Systematic Review and MetaAnalysis of Randomized Controlled Trials. Pain Physician. 2017;20(6):E755-96. 

9. Nutt D, King LA, Saulsbury W, Blakemore C. Development of a rational scale to assess the harm of drugs of potential misuse. Lancet. 2007;369(9566):1047-53. 

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