Research on Cannabis for Arthritis

Arthritis is a common affliction, affecting almost one-quarter of the US population. Current treatments provide inadequate relief and have serious side effects. This article highlights the latest research surrounding cannabis as an alternative to currently available therapeutics. The research on cannabis for arthritis is consistent with the same greater medical and social acceptance of cannabis use more generally.

Arthritis affects joints, causing pain, swelling, and stiffness. According to the US Center for Disease Control and Prevention (CDC), arthritis is the leading cause of disability among US adults and affects some 58.5 million people, or 23.7% of US adults, more women than men (1). There are two main types of arthritis: osteoarthritis and rheumatoid arthritis.

Osteoarthritis (OA), the most common type of arthritis, affects 32.5 million adults in the US (2). OA tends to occur more often in people: with a genetic predisposition; who are older, female, or have injured a joint; or who are heavier, and thus put more stress on knees, hips, and spine. OA involves wear-and-tear damage to a joint’s cartilage, which is the coating on the ends of bones that cushions movement between bones and enables smooth joint motion (see Figure 1). Damage to cartilage causes bones to grind together, leading to pain, swelling, and stiffness. This wear and tear can occur over time, or it can be accelerated by joint injury or infection (3).

Rheumatoid Arthritis (RA), the second most common type of arthritis, affects some 1.3 million people in the US (2). RA is an autoimmune disease, caused by a combination of elements, including genetic predisposition, environmental factors, and a dysfunctional immune system (4). In people with RA, the body’s immune system attacks the lining of the joint capsule, that is, the synovial membrane, which encloses all the joint parts, as seen in Figure 1. This membrane becomes inflamed and swollen, and as the disease progresses, it may cause destruction of cartilage and bone within the joint (3,4).

Current Treatments

Mild-to-moderate OA pain is generally treated with non-steroidal anti-inflammatory drugs (NSAIDs), but chronic use of NSAIDs may cause gastrointestinal (GI) or kidney problems. People who do not respond to NSAIDs or who suffer from severe OA pain may use opiates, but on-going opioid use may lead to tolerance and dependence (5).

There are four classes of therapeutics used to treat RA: biologic response modifiers (biologics), corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and NSAIDs (6). All of these therapeutics have the potential to cause side effects, especially with long-term use. More specifically, biologics may be carcinogenic; corticosteroids may cause osteoporosis, infections, and GI problems; DMARDs may cause liver damage; and as just discussed, NSAIDs may cause GI or kidney problems (7,8).

Patients would clearly benefit from the availability of alternative treatments for both OA and RA that are safe and effective, especially with long-term use.

Cannabis Mechanisms of Action for Arthritis

As noted, OA and RA involve pain, inflammation, and potential damage to cartilage or bone. Additionally, OA and RA patients often suffer from arthritis-induced insomnia, anxiety, and depression. We want to understand how cannabis can be used to address all these different symptoms of OA and RA.

Overview of the Endocannabinoid System

Let’s start by understanding more generally how cannabis creates its effects in our bodies. The endocannabinoid system (ECS) is the body system that cannabis acts on to create its effects. Our ECS consists of three distinct components.

First, chemical signals, or neurotransmitters, communicate with cells to tell them whether and how to act. Anandamide (AEA) and 2-AG are the primary neurotransmitters generated by our bodies that are part of the ECS. Our bodies use AEA to modulate pain and inflammation (9). Tetrahydrocannabinol (THC) and cannabidiol (CBD) in cannabis act as neurotransmitters on our ECS, and like AEA, both of these cannabinoids also modulate pain and inflammation (5).

The second component of our ECS is a set of enzymes produced by our bodies that break down neurotransmitters after they have served their purpose. Fatty acid amide hydrolase (FAAH) is the enzyme that breaks down AEA and THC, preventing them from acting.

The last component of our ECS is the collection of cell receptors upon which neurotransmitters act. Receptors receive the signals communicated by neurotransmitters and direct cells to act accordingly. The primary receptors for the ECS are CB1 receptors and CB2 receptors. While CB1 receptors are located throughout the body, they are densely populated throughout the brain and spinal cord. CB2 receptors are also located throughout the body, and they are densely populated within the immune system.

Now let’s turn to how cannabis can be used to act on our ECS to treat symptoms of OA and RA.

The ECS Modulates Joint Functioning

In vitro (lab) and in vivo (animal) studies have shown that CB1 and CB2 receptors, together with a variety of other receptors activated by cannabis, are located in joint tissues, such as cartilage, synovial membrane, and bone. Additionally, CB1 and CB2 receptors, together with higher-than-normal levels of AEA and 2-AG, have been found in synovial biopsies from patients with both advanced OA and RA. The presence of ECS receptors and neurotransmitters in joint tissues suggests our ECS plays a role in moderating both normal and arthritic joint functioning (5).

Mechanisms to Decrease Pain and Inflammation

As a quick aside, to review the body’s processes for inflammation and pain signal processing, any type of noxious stimulus in our bodies will cause inflammation. Our bodies respond by flooding the area with immune system cells to fight the stimulus or repair damage. The large number of cells in the area creates inflammation, and when those cells press against nerve endings, they cause the nerves to send signals to our brain. Our brain processes those signals, interprets them as pain, and communicates this information back to the nerve endings, which then throb or ache (10). Notably, all the excessive immune cells and activity in the area can also cause collateral damage to nearby tissue, which can exacerbate inflammation.

With that quick review in mind, there are several different mechanisms of action whereby cannabis can decrease pain and inflammation due to OA and RA. First, cannabis can reduce inflammation by reducing the flood of immune system cells to arthritic joints. That is, cannabis can activate CB2 receptors in arthritic joint tissue to modulate the flow of immune system cells in inflammation responses (5,11). Second, cannabis can reduce inflammation by reducing collateral tissue damage caused by OA or RA. Specifically, cannabis can activate CB2 receptors in joint tissue to modulate the flow of immune system cells in inflammation responses. By modulating inflammation, cannabis can reduce damage and destruction of arthritic joint tissues associated with excessive inflammation activity (5,11,12). Third, cannabis can reduce pain by reducing joint inflammation and thus pressure on nerve endings. It does this by activating CB2 receptors in arthritic joint tissues to prevent pain signals in the tissue from being sent to the brain (5). And fourth, cannabis can reduce pain by inhibiting pain processing signals received by the brain. Namely, cannabis can activate CB1 receptors in the brain to prevent processing of pain signals received from arthritic joint tissues (5).

Mechanisms to Decrease Comorbidities

Cannabis can reduce the burden of arthritis in patients by alleviating many of the comorbidities OA and RA patients often suffer from, including arthritis-induced insomnia, anxiety, and depression. Cannabis can reduce these conditions directly, by acting on CB1 and CB2 receptors in the brain (11). At the same time, by alleviating pain and inflammation associated with arthritis, cannabis can reduce arthritis-induced insomnia, anxiety, and depression.

Other Mechanisms of Action

As previously mentioned, our endogenously produced cannabinoid AEA can activate CB1 and CB2 receptors to reduce arthritis-induced pain, inflammation, insomnia, anxiety, and depression. As also previously mentioned, FAAH is the ECS enzyme that breaks down AEA and THC. Natural and synthetic cannabinoids are being researched for use in inhibiting FAAH production—to prevent the break-down of AEA and THC (5,11). These FAAH-inhibitors would thus make more AEA and THC available to inhibit or relieve pain, again either remotely in the brain or locally at the joints.

Potential Problems with Cannabis for Arthritis

Researchers have identified two potential problems with the use of cannabis—specifically THC—to address OA and RA (5,11). First, when THC acts on CB1 receptors in the brain, it induces psychoactive effects, which many patients do not want to experience. And second, when THC acts on CB1 receptors outside the central nervous system (CNS), it induces pro-inflammatory effects.

Researchers have tried to address the first problem of psychoactivity by using cannabis to selectively activate CB1 receptors peripherally, only to be stymied by THC’s pro-inflammatory cardiovascular and metabolic side effects. In response, researchers have considered addressing THC’s pro-inflammatory effects by using natural or synthetic cannabinoids to inhibit CB1 receptor activation. Unfortunately, these substances caused unfavorable psychiatric side effects.

Ongoing research is attempting to figure out how to reduce THC-induced psychoactivity, while preventing THC-induced cardiovascular inflammation.

Studies on Cannabis for Arthritis

Animal Studies

Miller and colleagues (5) stated: “Overall, there is strong support for the idea that the endocannabinoid system operates to limit pain in joint disease and that activation of this system with the appropriate cannabinoids is effective in limiting joint pain at both central and peripheral sites.” Specifically, mouse studies show that: CBD blocks arthritis progression by reducing joint swelling, pain, and tissue damage; CBD decreases joint damage and generates potent immunosuppressive and anti-inflammatory effects (13); and synthetic CBD reduces joint pain (5).

Surveys

Surveys tend to be relatively less dependable than other types of clinical data because self-reported information is notoriously unreliable, respondents tend to be biased, and there is no control group to help correct for placebo effects. Nevertheless, survey data can provide some useful information.

There are many surveys of medical cannabis patients generally, and also of arthritis patients specifically, that have been conducted to better understand both the characteristics of people who use cannabis for medical conditions, as well as these patients’ experiences and outcomes with cannabis. I’d like to review three different sets of patient surveys.

Surveys of Medical Cannabis Dispensary Patients

The first set of studies questioned people in medical dispensaries about their use of cannabis to treat medical conditions. Since these are current medical users, their success rates are expected to be relatively high, because if cannabis weren’t helping them feel better, then they would presumably not continue to use it.

Survey respondents in Canada (2013) (14), Arizona (2015) (15), and Los Angeles, California (2014) (16) from similar time periods all had very similar characteristics: they were predominantly white males with higher levels of income and education, and roughly 15–25% report using cannabis primarily to treat arthritis.

Almost all survey respondents in the Canadian study who use cannabis for arthritis report using it to address sleep, pain, inflammation, and most also treat anxiety and depression. Some medical patients (not just arthritis patients) reported using cannabis recreationally prior to initiating its use for medical purposes.

The majority of survey respondents in the Arizona study who use cannabis to address symptoms from arthritis report: obtaining relief with cannabis, obtaining better relief from cannabis than that from other medications, and reducing their use of other medications because of cannabis. Respondents in the LA study reported that they had used cannabis recreationally before later using it therapeutically, and they also reported obtaining cannabis products from other (non-medical) sources in addition to dispensaries.

Surveys of Arthritis Patients

The second set of studies surveyed arthritis patients to understand the portion of patients that use cannabis to treat arthritis, the differences between patients who use cannabis for arthritis and those who don’t, and the outcomes achieved from using cannabis to treat arthritis.

The first two studies were conducted online, where one assessed CBD use by arthritis patients in the US (17) and the other assessed marijuana or CBD use by arthritis patients in Europe (18). In contrast to respondents in the dispensary studies who were predominantly male, the online study respondents were predominantly female. The results showed that 70% of US respondents had tried CBD and more than half of European respondents had tried either cannabis or CBD to treat their arthritis. The vast majority of respondents who had tried cannabis reported that it had improved their symptoms, and most respondents in the US reported decreasing or ceasing the use of other medications. Two-thirds of Europeans, but less than half of Americans, had spoken to their doctors about their use of cannabis.

The third set of studies reviewed also consist of a set of two studies of arthritis patients. These studies were both conducted at the same rheumatology clinic, assessing patterns of use first in 2014 (19) and then again in 2019 (20) to see how the patterns had changed. These two studies provide three sets of information: what are the differences between patients who use cannabis to treat their arthritis and those who do not, how have those differences between users and non-users changed over time, and how has the incidence of cannabis use by arthritis patients changed over time. Let’s take each of these in turn.

Medical Cannabis Users Versus Nonusers

Both studies reported that patients who used cannabis for arthritis were more likely than non-users to be younger and unemployed or disabled, suffer from OA rather than RA, have greater levels of pain and disease severity, have greater use of opioids and other pain medications, be past or current cigarette smokers, and be past or current recreational cannabis users.

Medical Cannabis Users Over Time

Relative to those in 2014, 2019 patients who use cannabis to treat arthritis tended to be older, more female, more likely to have RA rather than OA, and less likely to be disabled or unemployed; have lower levels of pain; and be less likely to use opioids, to be cigarette smokers, or to be recreational cannabis users (see Figure 2).

Incidence of Medical Cannabis Use Over Time

Cannabis use by arthritis patients for medical uses doubled between 2014 and 2019 (see Figure 3). The percentage of arthritis patients who had ever used cannabis for medical uses increased between 2014 and 2019, from 4.3% to 8.2%, and the percentage of patients who currently use cannabis for medical uses increased from 2.8% to 6.5%. The percentage of patients who currently use cannabis for recreational uses also doubled, from 2.1% to 4.9%.

Concerns

In the 2019 study (20), researchers stated concerns that: “Most (80%) medical users were purchasing all or at least a portion of cannabis via a nonmedical route” and that “the treating physician was unaware of any cannabis use for two-thirds of the patients.” The researchers conceded that cannabis is not reimbursed by insurers, and cannabis purchased through nonmedical routes was generally much less expensive. Researchers were also concerned that many patients chose inhalation as their method of administration, while they noted that this may be a hold-over from their tendency to have had a history of smoking cigarettes. Finally, researchers noted that almost half of medical users in the 2019 study had discontinued their use of medical cannabis, due either to lack of effects or to unwanted side effects.

Clinical Trials

Only a few clinical trials of cannabis for arthritis have been conducted. One was a 2006 preliminary assessment of 58 patients conducted to assess the safety and efficacy of Sativex for RA, where Sativex is a cannabis therapeutic that received botanical drug approval in the UK in 2010. The study found Sativex improved pain and sleep (21). Another study, a randomized control trial (RCT), was conducted in 2022 on 18 patients to assess the efficacy of topical CBD for thumb joint arthritis. The study found CBD improved pain and disability (22). Finally, another 2022 RCT of 129 patients undertaken to assess the efficacy of CBD for OA and psoriatic arthritis found no effects on pain, sleep, depression, or anxiety (23). Three additional Canadian trials of cannabis for knee osteoarthritis have been registered with the National Institute of Health but have not (yet) been performed.

In Conclusion

Arthritis is a common affliction, affecting almost one-quarter of the US population. Current treatments provide inadequate relief and have serious side effects. An alternative to currently available therapeutics that provides relief without undue side effects would, undoubtedly, be quite welcome. The ECS has been shown to modulate pain and inflammation, and endocannabinoid receptors have been shown to pervade joint tissues. There are thus clear mechanisms of action for cannabis to provide relief for arthritis patients. While placebo-controlled randomized trials are lacking, a few early studies show promise for cannabis and arthritis. Significantly, surveys show that many arthritis patients are already finding relief using cannabis to treat their symptoms of arthritis. Noteworthy is the fact that over time, medical cannabis users are coming from more mainstream parts of the population. That is, earlier (2014) arthritis patients who used medical cannabis tended to come from more marginalized populations: they tended to be younger males, they had greater levels of symptoms severity, and they had more experience with cigarettes and recreational cannabis use. However, relative to these earlier patients, more recent patients (2019) have tended to be slightly older, more female, less severely disabled, and less experienced with cigarettes or recreational cannabis use. The research on cannabis for arthritis is thus consistent with the same greater medical and social acceptance of cannabis use more generally.

References

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18. Creaky Staff. 57% of Arthritis Patients Have Tried Marijuana or CBD for Medical Reasons (And More Than 90% Say It Helped) https://creakyjoints.org/eular-2019/medical-marijuana-cbd-usage-arthritis-patients-study/.
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22. Heineman, J. T. A Randomized Controlled Trial of Topical Cannabidiol for the Treatment of Thumb Basal Joint Arthritis https://pubmed.ncbi.nlm.nih.gov/35637038/.
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About the Author

Ruth Fisher, PhD, is a systems design researcher and analyst. She analyzes markets to determine how environments shape outcomes. She is co-founder of CannDynamics, and author of The Medical Cannabis Primer and Winning the Hardware-Software Game: Using Game Theory to Optimize the Pace of New Technology Adoption. Dr. Fisher has worked in the technology and healthcare sectors on behalf of technology companies, early-stage researchers, physicians, and technology start-ups.