Today we are going to learn about how CBD can be used to help with arthritis symptoms.
We reviewed clinical and preclinical studies that looked at:
- The potential anti-inflammatory and analgesic properties of CBD
- What mechanisms of action give CBD its anti-arthritic properties
- How different CBD products are processed in your body
At the end of this article, you will learn how CBD interacts with your body and what types of CBD oils are best for arthritis.
Table of contents:
How Might CBD Reduce Arthritis?
Cannabidiol (CBD) is one of 113 phytocannabinoids (pCBs) found in the species Cannabis sativa. THC and CBD are the two most abundant pCBs in Cannabis plants (16). Both compounds have a myriad of therapeutic effects.
One major difference between THC and CBD is that unlike the former, CBD has no psychoactive effects (13).
Like other pCBs, CBD interacts with the Endocannabinoid System (ECS). This system helps regulate the nervous system, immune function, and homeostasis (18).
The ECS is not unique to humans. It can be found in many animals, including all vertebrates.
The body makes its own cannabinoids (e.g. anandamide) that bind to ECS receptors, but pCBs can also interact with them (16)
Two receptors that are part of the ECS are:
- Cannabinoid receptor 1 (CB1)
- Cannabinoid receptor 2 (CB2)
CBD interacts with both CB1 and CB2 by acting as an indirect antagonist. CBD also inhibits the uptake of endocannabinoids, and can even reverse the psychoactive effects of THC by interacting with CB1 (8).
How is the ECS related to arthritis?
The ECS is known to regulate pain, inflammation, and joint homeostasis (2) (16). Both CB1 and CB2 are expressed in different joint tissues, and CB2 has been tied to regulating joint pain specifically.
Aside from joint pain, people with arthritis can also have:
- Neuropathic pain;
- Inflammation;
- Joint degeneration;
- Decreased range of motion
CBD interacts with receptor types outside the ECS that are related to these symptoms, including:
- Transient receptor proteins (TRP);
- Peroxisome proliferator-activated receptors (PPAR);
- Alpha-3 glycine;
- Serotonin 5-HT receptors;
- Adenosine A2A;
- Opioid receptors
CBD reduces arthritis pain and inflammation by activating vanilloid receptors
Like cannabinoid receptors in the ECS, TRPs help regulate pain and inflammation.
TRP and CB2 receptors occur co-locally and regulate joint pain by working through many of the same signaling pathways.
The vanilloid receptors TRPV1 and TRPA1 are TRPs that process painful stimuli and mediate inflammatory and chronic pain responses.
When activated, they produce a heightened sense of pain. Both of these receptors heavily influence the development of Osteoarthritis (18).
TRPV1 expression increases after inflammation, prompting the release of the TNF-a signaling protein. This increases TRPV1 expression in joint cells, which leads to more inflammation (9).
This is especially relevant for arthritis because TNF-a is highly expressed in joint tissues in animal models of arthritis (3).
CBD disrupts this inflammatory pathway by potently binding to TRPV2 and TRPA1 receptors. This results in reduced release of TNF-a and lower pain sensitivity (7).
CBD Activates Serotonin Receptors Tied to Pain Regulation
Serotonin 5-HT receptors are involved in CBD's analgesic effects (19)
For example, the Serotonin 5-HT1A receptor plays a critical role in pain regulation and relief. CBD is a strong activator of 5-HT1A, which results in pain reduction (11)
5-HT2A and 5-HT3A receptors can also be regulated by CBD to a lesser degree (22) (16).
CBD Reduces Neuroinflammation Associated with Arthritis
The Adenosine A2A receptor is known to affect neurogenic inflammation, a common symptom of Rheumatoid Arthritis (RA) and Osteoarthritis (OA).
CBD helps relieve this symptom by acting as an agonist at the A2A receptor. In other words, it binds to this receptor, inhibiting adenosine transport and uptake.
Adenosine agonists and uptake inhibitors have anti-inflammatory action. So, CBD reduces neuroinflammation because it is an adenosine agonist. So is THC, but it is less potent in this regard (4)
Multiple preclinical animal studies have shown that CBD can reduce neuroinflammation. However, CBD does not just act on the A2A receptor. It also interacts with these receptors:
- TRPV1
- Serotonin 5-HT1A
- GPR55 (1)
More Receptor Interactions with CBD
Alpha-3 glycine receptors are a known target for pCBs. These receptors mediate how CBD and pCBs similar in chemical structure suppress chronic pain (24).
Opioid receptors regulate pain relief and are a common target of arthritis medications.
Lastly, CBD indirectly regulates opioid receptors by increasing the activity of other proteins that bind to these receptors.
So, if CBD is taken alongside compounds that target these receptors, it may increase their effectiveness.
CBD and Conventional Arthritis Drug Interactions
Because of how CBD interacts with opioid receptors, it may increase the effectiveness of other arthritis drugs that target these receptors (19).
This synergistic effect extends to anti-rheumatic drugs as well (12).
Pain relief is the most commonly cited reason for Cannabis use.
Many conventional pain relievers increase the activity of the ECS.
Pain relief is the most commonly cited reason for Cannabis use. Unlike opiates, cannabinoid-based pain relievers do not cause respiratory depression (6).
Review of Studies That Found Anti-Arthritic Effects Associated with CBD
Preclinical Studies
A 2015 study investigated how CBD may relieve pain and swelling in a rat arthritis model. Groups of rats were given varying doses of a CBD topical application. Their findings revealed two things:
- Topical CBD reduced joint swelling and spontaneous pain
- The product's relieving effects were dose-dependent
In another study, a locally injected CBD dose was given to rats induced with OA. CBD reduced inflammation and neuropathic pain in the treatment group (18).
Body-wide CBD treatments in these animals have shown the anti-inflammatory properties of CBD.
As mentioned before, the TNF-a protein promotes inflammation and is a mediator of arthritis. Mice treated with low doses of CBD have slower TNF-a production (4).
This effect has been shown in another study with mice treated with CBD after showing symptoms of collagen-induced arthritis, a proxy for Rheumatoid Arthritis (RA) in humans. CBD suppressed TNF-a in both treatment types (14)
Clinical Studies
What research has been done on the anti-inflammatory properties of CBD is promising.
Repeated CBD administration is known to reduce levels of Rheumatoid Arthritis Synovial Fibroblasts (RASF). These are pro-inflammatory cytokines that contribute to RA.
In a 2020 study, RA patients were treated with CBD to see what effect it has on RASFs. What did they find?
CBD reduced the viability of these cells by binding to TRPA1 and mitochondrial targets (12).
One study gave 7 patients moderate doses of CBD twice daily, and the results were:
- Total pain improvement in 2 patients
- Partial pain improvement in 4 patients
- No pain improvement in 1 patient (5)
Clinical Findings that Contradict Previous CBD Research
A 2021 clinical study investigated the effects of CBD on pain intensity. One group was given oral CBD tablets, and the other received a placebo. Compared to the control group, patients treated with CBD did not have a significant reduction in pain intensity (21).
In another 2021 study, CBD actually promoted inflammation. Patients with RA and Psoriatic Arthritis (PA) were treated with CBD to test its effects on pro-inflammatory Th17 cells. These cells play a critical role in the development of PA and spinal arthritis.
In some patients and in vitro, CBD led to increases in Th17 cells. This finding directly contradicts previous findings in mice (10).
In a small clinical trial, patients given CBD orally were asked to rate pain sensation after treatment. CBD was not found to have a reliable pain-relieving effect. This is consistent with some past studies that have used CBD isolate (1)
Currently, relatively little clinical research has been done on CBD as a potential treatment for types of arthritis.
Growing public interest in CBD has far outpaced the medical information that comes from clinical studies (17). There is a great need for large-scale clinical research on how CBD might help with arthritis symptoms.
What’s the Best CBD Oil for Arthritis Relief?
Epidiolex is the only FDA-approved CBD isolate oil that can be prescribed, but is used only to treat seizures and not arthritis.
On a positive note, many edible CBD oils are commercially available. They typically fall into 3 categories:
- CBD Isolate
- Broad Spectrum
- Full Spectrum
Isolate oils only contain purified CBD and have neither terpenes nor additional pCBs. Broad and full-spectrum oils both contain terpenes and minor pCBs, but only full-spectrum oils contain THC.
In combination with other pCBs (e.g. THC, CBG) and secondary compounds like terpenes, CBD can produce a synergy known as the entourage effect (15).
If your goal is to maximize this effect, then a full spectrum product would work best.
Also THC is a more proven pain-reducing compound than CBD. THC also has potent anti-inflammatory effects.
Anyone using CBD for pain- and inflammation-related conditions would benefit from having some THC inside their product.
To learn what CBD oil is right for you, check out this article.
How to Use CBD Products for Arthritis
There are several different types of CBD products:
- Edible oils, capsules, and gummies;
- Vape oils;
- Cannabis flower strains dominant in CBD
- Topical products
- Oromucosal sprays
The amount of CBD that gets absorbed into your bloodstream (bioavailability) depends on your use method.
Oral and Sublingual CBD Products
Orally taken CBD has a low bioavailability but stays in your body the longest. When taken this way, CBD undergoes first-pass metabolism in the liver.
Because of this, less CBD is absorbed by your body compared to other CBD product types.
You can work around this problem by using edible CBD oils sublingually. This method avoids first-pass metabolism and is more rapidly absorbed than oral CBD (9).
To use CBD sublingually, apply the edible CBD oil under your tongue and keep it there for at least 60 seconds, then swallow it.
Topical CBD Products
CBD topical products are especially helpful for joint inflammation and pain because they can be locally applied.
Topicals avoid the first-pass metabolism problem with oral products, so more CBD can be absorbed. However, you must choose the right kind of topical product.
CBD is highly lipophilic so it tends to dissolve before penetrating the skin barrier and entering your bloodstream (20).
Topical CBD can be delivered more effectively with nanovesicles:
If you encapsulate the CBD in a carrier oil, it can be carried across the skin and more CBD will be absorbed (8).
With topicals, you simply rub them into the affected area. CBD topicals typically stay in your system for 2-5 days.
Interested in CBD Topicals? Click this link.
Oral and Sublingual CBD Products
Orally taken CBD has a low bioavailability but stays in your body the longest. When taken this way, CBD undergoes first-pass metabolism in the liver.
Because of this, less CBD is absorbed by your body compared to other CBD product types.
You can work around this problem by using edible CBD oils sublingually. This method avoids first-pass metabolism and is more rapidly absorbed than oral CBD (9).
For oral products, CBD concentration peaks between 2 – 5 hours.
Using CBD Oil for Vaping
Compared to edible CBD products and topicals, vaping CBD is the most quick-acting method, but leaves your body the fastest.
CBD concentration often peaks within 10 minutes and has a bioavailability of 30% (8).
Do not use edible CBD oil for vaping; it can cause pneumonia. Choose oils specifically made for vaping CBD.
Related: How to Use CBD Oil for Pain
How to Dose CBD Oil for Arthritis
From research on animal models, we know that the pain-relieving effects of CBD are dose-dependent (9).
CBD is safe and well-tolerated in adults in doses up to 1600 mg (5).
Based on one study, a dose of 100 – 300 mg CBD has pain-relieving effects.
However, these results are for orally taken CBD. Keep in mind that if you use edible CBD oil at these doses, you will quickly run out.
Tip: Taking CBD oil within 2 hours of a meal results in more absorption (20).
As stated before, the method of use will affect how much CBD is absorbed.
Click here for a more detailed explanation on CBD dosages.
Step-By-Step Guide for Using Edible CBD Oil
- Select a full-spectrum CBD oil
- Take your CBD oil within 2 hours of a meal that includes healthy fats
- Drop a 25 mg dose of CBD under your tongue
- Hold this dose for 60 seconds, then swallow it
- Wait at least 8 hours before taking a second dose. Alternatively, you can take the oil in smaller doses throughout the day
- In case of no effect, slowly increase the dosage by 10 mg increments until a maximum dose of 100 mg CBD.
What's Next…
Go to our CBD Hub to learn more about CBD-related topics.
Scientific References:
- Arout, C. A., Haney, M., Herrmann, E. S., Bedi, G., & Cooper, Z. D. (2021). A placebo‐controlled investigation of the analgesic effects, abuse liability, safety and tolerability of a range of oral cannabidiol doses in healthy humans. British Journal of Clinical Pharmacology, 88(1), 347–355. https://doi.org/10.1111/bcp.14973
- Baswan, S. M., Klosner, A. E., Glynn, K., Rajgopal, A., Malik, K., Yim, S., & Stern, N. (2020). Therapeutic potential of cannabidiol (CBD) for skin health and disorders. Clinical, Cosmetic and Investigational Dermatology, Volume 13, 927–942. https://doi.org/10.2147/ccid.s286411
- Burstein, S. (2015). Cannabidiol (CBD) and its analogs: A review of their effects on inflammation. Bioorganic & Medicinal Chemistry, 23(7), 1377–1385. https://doi.org/10.1016/j.bmc.2015.01.059
- Carrier, E. J., Auchampach, J. A., & Hillard, C. J. (2006). Inhibition of an equilibrative nucleoside transporter by Cannabidiol: A mechanism of cannabinoid immunosuppression. Proceedings of the National Academy of Sciences, 103(20), 7895–7900. https://doi.org/10.1073/pnas.0511232103
- Cuñetti, L., Manzo, L., Peyraube, R., Arnaiz, J., Curi, L., & Orihuela, S. (2018). Chronic pain treatment with cannabidiol in kidney transplant patients in Uruguay. Transplantation Proceedings, 50(2), 461–464. https://doi.org/10.1016/j.transproceed.2017.12.042
- Darkovska-Serafimovska, M., Serafimovska, T., Arsova-Sarafinovska, Z., Stefanoski, S., Keskovski, Z., & Balkanov, T. (2018). Pharmacotherapeutic considerations for use of cannabinoids to relieve pain in patients with malignant diseases. Journal of Pain Research, Volume 11, 837–842. https://doi.org/10.2147/jpr.s160556
- De Petrocellis, L., Ligresti, A., Moriello, A. S., Allarà, M., Bisogno, T., Petrosino, S., Stott, C. G., & Di Marzo, V. (2011). Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. British Journal of Pharmacology, 163(7), 1479–1494. https://doi.org/10.1111/j.1476-5381.2010.01166.x
- Fitzcharles, M. A., Clauw, D. J., & Hauser, W. (2020). A cautious hope for Cannabidiol (CBD) in rheumatology care. Arthritis Care & Research. https://doi.org/10.1002/acr.24176
- Hammell, D. C., Zhang, L. P., Ma, F., Abshire, S. M., McIlwrath, S. L., Stinchcomb, A. L., & Westlund, K. N. (2015). Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. European Journal of Pain, 20(6), 936–948. https://doi.org/10.1002/ejp.818
- Kotschenreuther, K., Waqué, I., Yan, S., Meyer, A., Haak, T., von Tresckow, J., Schiller, J., Gloyer, L., Dittrich-Salamon, M., & Kofler, D. M. (2020). Cannabinoids drive th17 cell differentiation in patients with rheumatic autoimmune diseases. Cellular & Molecular Immunology, 18(3), 764–766. https://doi.org/10.1038/s41423-020-0437-4
- Lindstedt, F., Karshikoff, B., Schalling, M., Olgart Höglund, C., Ingvar, M., Lekander, M., & Kosek, E. (2012). Serotonin-1A receptor polymorphism (RS6295) associated with thermal pain perception. PLoS ONE, 7(8). https://doi.org/10.1371/journal.pone.0043221
- Lowin, T., Tingting, R., Zurmahr, J., Classen, T., Schneider, M., & Pongratz, G. (2020). Cannabidiol (CBD): A killer for inflammatory rheumatoid arthritis synovial fibroblasts. Cell Death & Disease, 11(8). https://doi.org/10.1038/s41419-020-02892-1
- Khaleghi, M. (2020). New arthritis foundation guidelines on CBD use could be first of many more to come. Alternative therapies in health and medicine. Retrieved May 9, 2022, from https://pubmed.ncbi.nlm.nih.gov/32035005/
- Malfait, A. M., Gallily, R., Sumariwalla, P. F., Malik, A. S., Andreakos, E., Mechoulam, R., & Feldmann, M. (2000). The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proceedings of the National Academy of Sciences, 97(17), 9561–9566. https://doi.org/10.1073/pnas.160105897
- McPartland, J. M., & Russo, E. B. (2001). Cannabis and cannabis extracts. Journal of Cannabis Therapeutics, 1(3-4), 103–132. https://doi.org/10.1300/j175v01n03_08
- Miller , R. J., & Miller, R. E. (2017). Is cannabis an effective treatment for joint pain? Clinical and experimental rheumatology. Retrieved May 9, 2022, from https://pubmed.ncbi.nlm.nih.gov/28967368/
- Pathak, N., Radford, Z. J., Kahan, J. B., Grauer, J. N., & Rubin, L. E. (2022). Publication frequency and google trends analysis of popular alternative treatments to arthritis. Arthroplasty Today, 14, 76–80. https://doi.org/10.1016/j.artd.2021.12.009
- Philpott, H. T., O'Brien, M., & McDougall, J. J. (2017). Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis. Pain, 158(12), 2442–2451. https://doi.org/10.1097/j.pain.0000000000001052
- Russo, E. B., Burnett, A., Hall, B., & Parker, K. K. (2005). Agonistic properties of cannabidiol at 5-HT1A receptors. Neurochemical Research, 30(8), 1037–1043. https://doi.org/10.1007/s11064-005-6978-1
- Silmore, L. H., Willmer, A. R., Capparelli, E. V., & Rosania, G. R. (2021). Food effects on the formulation, dosing, and administration of cannabidiol (CBD) in humans: A systematic review of Clinical Studies. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 41(4), 405–420. https://doi.org/10.1002/phar.2512
- Vela, J., Dreyer, L., Petersen, K. K., Arendt-Nielsen, L., Duch, K. S., & Kristensen, S. (2021). Cannabidiol treatment in hand osteoarthritis and psoriatic arthritis: A randomized, double-blind, placebo-controlled trial. Pain, Publish Ahead of Print. https://doi.org/10.1097/j.pain.0000000000002466
- Watkins, A. R. (2019). Cannabinoid interactions with ion channels and receptors. Channels, 13(1), 162–167. https://doi.org/10.1080/19336950.2019.1615824
- Xiong, W., Cui, T., Cheng, K., Yang, F., Chen, S.-R., Willenbring, D., Guan, Y., Pan, H.-L., Ren, K., Xu, Y., & Zhang, L. (2012). Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors. Journal of Experimental Medicine, 209(6), 1121–1134. https://doi.org/10.1084/jem.20120242
