Rheumatic diseases – also called “rheumatism” – are a collective term for various diseases of the musculoskeletal system. In addition to joints, muscles, tendons, bones and connective tissue can also be involved. Arthrosis (joint wear and tear) means progressive destruction of joint cartilage. Arthritis (joint inflammation) often occurs in rheumatic diseases such as fibromyalgia, rheumatoid arthritis, gout, lupus or acute arthrosis. Possible symptoms of joint inflammation and degeneration include morning stiffness, pain at rest and during movement, swelling, and sleep disturbances. Medicinal cannabis can assist with these symptoms. Cannabis acts as a natural mixture of various plant constituents: phytocannabinoids such as psychotropic tetrahydrocannabinol (THC) and non-psychotropic cannabidiol (CBD), terpenes and flavonoids.
Surveys and reviews with patients of various rheumatic diseases such as rheumatoid arthritis or metacarpophalangeal joint arthritis of the thumb show, that THC and CBD can relieve pain and inflammation as well as improve sleep. Recent surveys show that medical cannabis is increasingly used for rheumatic diseases.
Osteoarthritis and rheumatoid arthritis (rheumatism) – the most common joint diseases
Arthrosis (joint wear and tear) or also called Osteoarthritis is the most common rheumatic disease, affecting over 5 million people in Germany. It can affect any joint. This degenerative joint disease leads to progressive wear of the joint cartilage, which is why older people are particularly affected: Among those over 65, half of women and one-third of men suffer from osteoarthritis. Younger individuals can also become ill, for example as a result of congenital deformities, accidents or heavy work [1]. Other joint diseases can lead to joint wear as a secondary disease.
Arthritides (joint inflammations) can also occur at any joint. The causes can be manifold, such as infections, rheumatic diseases, metabolic diseases as well as activated arthrosis (acute inflammatory arthrosis). The mostly chronic inflammatory diseases include more than 100 clinical pictures. Often they are autoimmune diseases: The misdirected immune system therefore attacks the body’s own tissue – as in this case the joint cartilage. The most common is rheumatoid arthritis, which is accompanied by painful synovitis (inflammation of the joint mucosa) and affects 0.5 to 0.8 of adults in Germany [2].
Arthrosis
Experts distinguish between primary arthrosis, which has no clear underlying cause, and secondary arthrosis, a secondary disease of other joint diseases and injuries. Excess weight, heavy lifting and physically demanding work increase the risk of arthrosis. Often only one joint (monoarthrosis) or a few joints (polyarthrosis) are affected [3].
The first signs of incipient arthrosis are restricted movement and pain. Initially, inflammation does not occur, which is why experts speak of latent arthrosis. Stiff joints in the morning and start-up pain (pain at the beginning of movement) are typical. As joint destruction progresses, painful inflammatory phases, so-called activated arthrosis, become more frequent. The inflamed joint mucosa leads to swelling, pain, hyperthermia, redness, a feeling of tension and increasing functional limitations. Cold and wet weather conditions often aggravate the symptoms. A typical feature is the alternation between phases of the disease with few symptoms and phases of inflammation, which persists for years. Until finally the joint is so severely destroyed that permanent pain and severe functional disorders are the result. Experts now speak of decompensated arthrosis. Even the smallest movements hurt. Pain at rest and chronic pain can also occur [3].
Arthrosis often affects knee, hip and finger joints. The following joints can be affected sein [1,3]:
- knee joint (Gonarthrosis)
- hip joint (Coxarthrosis)
- shoulder joint (Omarthrosis)
- vertebral joints (Spondylarthrosis)
- finger middle joint (Bouchard-Arthrosis)
- finger end joint (Herberden-Arthrosis)
- thumb sattle joint (Rhizarthrosis)
Arthritis
Arthritis manifests itself in painfully swollen joints, often with a pressure pain. The cause is inflammation of the synovial membrane (synovitis). A joint effusion (increased accumulation of fluid in the joint) may also be present. The joint is red and warm. Autoimmune diseases such as rheumatoid arthritis are frequent triggers of joint inflammation, which is why complaints – in contrast to arthrosis – also occur independently of physical stress. Joint inflammation is only present in activated osteoarthritis [4].
Rheumatoid Arthritis (RA) often affects hand, finger and foot joints [4]. Typical complaints are severe morning stiffness (lasting more than an hour) and flu-like symptoms. Chronic polyarthritis is often present, i.e. several joints are inflamed symmetrically on both sides of the body. Affected individuals often have so-called rheumatoid nodules (thickenings under the skin) and show characteristic changes on X-ray [2]. Rheumatic diseases can also affect other organs such as the skin and eyes; experts refer to these as extra-articular manifestations. Psoriatic arthritis, for example, also involves psoriasis of the skin.
Some rheumatologic diseases that may be associated with joint inflammation are [2,5,6]:
- rheumatoid arthritis (RA)
- back pain of degenerative cause
- osteoarthritis
- fibromyalgia
- systemic lupus erythematodes (SLE)
- ankylosing spondylitis (Morbus Bechterew) [2,5]
- arthrosis [6]
- gout [6]
- psoriasis-arthritis [6]
- juvenile idiopathic arthritis [6]
Cannabis in rheumatism
Cannabinoids have been used medicinally for thousands of years. As early as 2,800 BC, people used cannabis for rheumatism. Today, many data support the positive effects for pain relief. The multitude of plant constituents, besides phytocannabinoids especially terpenes and flavonoids, act synergistically or antagonistically together. Phytocannabinoids such as THC and CBD act on cannabinoid receptors of the endocannabinoid system: cannabinoid receptors are found in the central nervous system and on peripheral tissues. Centrally, they are involved in pain perception, among other things; peripherally, they serve on nociceptive nerves for pain transmission. Many therapeutic effects, such as pain relief, can be achieved by activating the numerous CB1 receptors. In contrast, CB2 receptors are mainly formed on immune cells, which, among other things, control inflammation [7]. By activating cannabinoid receptors, medicinal cannabis can relieve pain and inflammation in rheumatic diseases.
Medicinal Cannabis in Arthritis
Review: Many people with rheumatic diseases use cannabis
French researchers analyzed the evidence on medicinal cannabis for painful rheumatic diseases in a review published in 2021. Studies published in English or French through June 2020 were reviewed. The science team found that cannabis use is increasing: Out of 10,873 people, 2,900 sufferers (about 20 percent) reported having experience using cannabis to relieve symptoms. One in six rheumatism patients (15.3 percent) currently use cannabinoids with good pain-relieving effects. Cannabis users had a higher pain intensity and were younger on average (58.4 years compared to 63.6 years) than those without cannabis use.
In particular, people with fibromyalgia frequently use cannabinoids: In four studies of fibromyalgia, two-thirds of subjects (68.2 percent in 611 subjects) used cannabis, compared with one-quarter (26 percent in 8,168 subjects) in seven studies of subjects with rheumatoid arthritis and lupus. Patients with cannabis use reported reduced pain intensity: compared to baseline, complaints on the analog scale (from 0 to 10) decreased significantly from 8.2 to 2.9. Rheumatism patients use cannabis for various reasons: For pain relief, anxiety relief, sleep disorders, or recreational purposes. The increased use in fibromyalgia might be related to accompanying psychological symptoms such as anxiety and alexithymia (emotional blindness). Sleep disturbances are a particularly big problem in rheumatism patients: a study showed that two-thirds struggle with insomnia and one-fifth have sleep disturbances. Therefore, especially the effect of cannabinoids on sleep disorders should be researched [8].
Double-blind study: THC and CBD improve pain, sleep quality and inflammatory activity in rheumatoid arthritis patients
An English double-blind study published in 2005 showed that Sativex, an oral spray containing THC and CBD, relieved pain from rheumatoid arthritis. The 58 participants took cannabinoid or placebo spray under the tongue (sublingually) in the evening for five weeks. The next morning, sleep quality, morning stiffness, rest and movement pain, and side effects were assessed.
Movement and rest pain decreased significantly: cannabis was able to reduce movement pain from an initial 7.0 to 4.8 and rest pain from 5.3 to 3.1. Therefore, movement and rest pain decreased by 2.2 under cannabis therapy. Under placebo, on the other hand, movement pain decreased by only 1.4 and rest pain by 1.2. Disease activity also benefited from the anti-inflammatory effect: disease activity (measured by DAS28) decreased from 5.9 to 5.0 under cannabinoid spray, indicating that cannabis influences the immune system. In the placebo group, only a decrease of 0.1 (decrease from 6.0 to 5.9) was recorded. These data suggest that cannabinoids relieve peripheral movement pain and attenuate central rest pain. However, no effect was found on morning stiffness.
Participants in the cannabis group also slept better: while sleep disturbances improved from 5.7 to 3.4 under cannabis, sleep improved only from 5.8 to 4.6 under placebo. The researchers hypothesize that cannabis improves sleep quality by alleviating nighttime discomfort.
The therapy was well tolerated with mild to moderate side effects: The most common were dizziness, headache, and dry mouth. Mild and transient dizziness occurred in 26 percent (8 of 31 subjects). Overall, cannabis medications were shown to be supportive in rheumatoid arthritis. Sativex significantly reduced pain and disease activity. According to the research team, taking it in the evening has the advantage of “sleeping through” side effects. However, larger and longer studies are needed [9].
Medicinal Cannabis in Arthrosis
Survey: sufferers with thumb metacarpophalangeal joint arthritis report pain relief from oral and topical cannabinoids
Researchers at the University of Virginia investigated cannabis use among patients with osteoarthritis of the thumb basal joint in a survey published in 2021. The research team was particularly interested in experiences with medical cannabis, such as pain-relieving effects and different dosage forms, as well as differences in disease characteristics between patients with and without cannabis use. For this purpose, affected persons were called for the survey between May and June 2020, which was completed by 103 persons. In addition, available medical records were evaluated to capture factors such as initial diagnosis, age, and prior treatment.
One in four and one in five respondents, respectively, reported having used cannabis products to relieve symptoms: A quarter (25 percent) had experience with oral cannabis medications, and about a fifth (21 percent) had tried topical cannabis products.
A large number of cannabis patients surveyed reported decreasing pain: almost half (12 of 25 people) reported that oral cannabinoids relieved arthritis pain. For one-third (7 of 21 people), topical cannabis preparations were able to control pain.
A clear majority is open to cannabis therapy: Oral cannabis medication would be taken by 69 percent of respondents, while topical cannabinoid treatment would be considered by as many as 80 percent. The research team summarized that numerous patients with painful metacarpophalangeal joint arthritis of the thumb use cannabis products. Further research is therefore needed [10].
Double-blind study: Cannabidiol (CBD) alleviates symptoms in domestic dogs with osteoarthritis
In 2020, American researchers found that cannabidiol (CBD) alleviates symptoms in a double-blind study involving 20 domestic dogs with veterinarian-diagnosed osteoarthritis. Before the study began, the scientific team conducted studies on animal and human cell cultures, as well as a mouse study. A bioequivalence study was conducted on healthy subjects using different CBD preparations.
- CBD reduces the production of the inflammatory messenger TNF-alpha in animal and human cell cultures of white blood cells: With lipopolysaccharides (LPS) – pro-inflammatory bacterial components – inflammation was triggered “in the test tube”, causing TNF-alpha to increase. Treatment of human cells with CBD prevented the increase in TNF-alpha by up to 97 percent, depending on the cell type.
- CBD reduces local and systemic inflammation in a mouse model: Application of croton oil to the mouse ear induced local inflammation manifested by redness (erythema), swelling (edema), white blood cell migration, and a TNF-alpha increase. Two and four hours after application of CBD, inflammatory signs (myeloperoxidase and TNF-alpha) and swelling decreased significantly. In another mouse model, lipopolysaccharide injected intraperitoneally (into the peritoneum) was shown to induce systemic inflammation, resulting in a sharp increase in the inflammatory substances TNF-alpha and interleukin, which are also involved in arthritis. Both intraperitoneal and topical CBD reduced inflammatory messengers in a dose-dependent manner.
- Liposomal CBD drugs are better absorbed by the body after oral administration, so they have a higher bioavailability than conventional CBD formulations: Because cannabinoids are fat-soluble, they are poorly absorbed orally, which can reduce therapeutic effects. Pharmaceutical technologists have developed techniques to improve the oral bioavailability of fat-soluble drugs: Active ingredients are “packaged” in so-called liposomes – nanometer-sized spheres of phospholipids (e.g. derived from sunflowers) with both fat-soluble and water-soluble properties. In mouse experiments, the liposomal CBD preparation alleviated inflammation triggered by lipopolysaccharides (LPS) more effectively than “normal” CBD, an indication of the better absorption of the liposome preparation. This advantage was also seen in humans: Five healthy subjects each received the same dose of CBD as either the “normal” or liposomal formulation on two study days. One hour later, liposomal CBD resulted in significantly (up to 17-fold) higher cannabinoid levels.
- CBD improves quality of life in pet dogs diagnosed with osteoarthritis with a good safety profile: 20 pet dogs suffering from osteoarthritis received either placebo, a conventional CBD formulation (low or high dose) or low-dose liposomal CBD. Pet owners and treating veterinarians assessed symptoms prior to study initiation and periodically throughout the course of the study. The study showed that placebo and low-dose CBD did not significantly alleviate symptoms. In contrast, high-dose CBD and low-dose liposomal CBD significantly reduced pain, with the effect lasting an additional 15 days after discontinuation. Veterinary studies demonstrated improvement in rising from a sitting or lying position, walking, and running.
Researchers came to the conclusion:
“Thus, an extrapolation of these findings suggest that CBD could be useful for treating pain and improving quality of life in humans with an affirmative diagnosis of osteoarthritis and/or other inflammatory conditions that might be ameliorated by a reduction in proinflammatory cytokines and pathologic neutrophil activity.”
Moreover, the study on the bioavailability of CBD compared to liposomal CBD shows:
“The data demonstrated a 17-fold increase in bioavailable circulating CBD following oral administration of the liposomal formulation as compared to the naked isolate.”
Conclusion: rheumatism and cannabis
Many sufferers of rheumatic diseases use cannabis to relieve pain and inflammation associated with osteoarthritis and arthritis. A cannabinoid spray containing THC and CBD can improve morning stiffness, pain, and sleep quality in rheumatoid arthritis, as well as reduce inflammation [9]. Surveys of patients with thumb base joint osteoarthritis show that oral and topical cannabinoids can relieve pain [10]. A veterinary study in domestic dogs suggests that nonpsychotropic CBD-particularly as a more bioavailable liposomal formulation-improves mobility and quality of life in osteoarthritis [11]. Recent reviews show widespread use of cannabinoids in a wide variety of rheumatic diseases, including rheumatoid arthritis, lupus, and fibromyalgia. Sufferers benefited from the pain-relieving and sleep-inducing effects of cannabis [8]. Therefore, George Habib’s team of researchers also states that cannabis should be seriously considered for any chronic pain disorder when accepted treatments are not sufficient to alleviate the pain and sleep problems of sufferers [12].
Sources:
[1] Pharmazeutische Zeitung. Knorpel und Knochen in Bedrängnis, Abruf 1.8.2022
[2] Robert Koch Institut. Entzündlich-rheumatische Erkrankungen, Abruf 1.8.2022
[3] Robert Koch Institut. Arthrose, Abruf 1.8.2022
[4] AWMF. Interdisziplinäre Leitlinie. Management der frühen rheumatoiden Arthritis, Abruf 1.8.2022
[5] Guillouard M, Authier N, Pereira B, Soubrier M, Mathieu S. Cannabis use assessment and its impact on pain in rheumatologic diseases: a systematic review and meta-analysis. Rheumatology (Oxford). 2021;60(2):549-556. doi:10.1093/rheumatology/keaa534
[6] https://www.gelbe-liste.de/rheumatologie/rheumatische-erkrankungen
[7] Blake DR, Robson P, Ho M, Jubb RW, McCabe CS. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology (Oxford). 2006;45(1):50-52. doi:10.1093/rheumatology/kei183
[8] Guillouard M, Authier N, Pereira B, Soubrier M, Mathieu S. Cannabis use assessment and its impact on pain in rheumatologic diseases: a systematic review and meta-analysis. Rheumatology (Oxford). 2021;60(2):549-556. doi:10.1093/rheumatology/keaa534
[9] Blake DR, Robson P, Ho M, Jubb RW, McCabe CS. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology (Oxford). 2006;45(1):50-52. doi:10.1093/rheumatology/kei183
[10] Fader L, Scharf Z, DeGeorge BR Jr. Assessment of Medical Cannabis in Patients With Osteoarthritis of the Thumb Basal Joint [published online ahead of print, 2021 Dec 7]. J Hand Surg Am. 2021;S0363-5023(21)00691-2. doi:10.1016/j.jhsa.2021.10.018
[11] Verrico CD, Wesson S, Konduri V, et al. A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain. Pain. 2020;161(9):2191-2202. doi:10.1097/j.pain.0000000000001896
[12] Habib, G., Khazin, F., & Artul, S. The Effect of Medical Cannabis on Pain Level and Quality of Sleep among Rheumatology Clinic Outpatients. Pain Research and Management, 2021, 1–6. https://doi.org/10.1155/2021/1756588