Medical Cannabis and Autoimmune Disease
An autoimmune disease or disorder is a condition where your immune system attacks your own body. Usually, the immune system recognizes the difference between foreign invaders (pathogens such as bacteria and viruses), but in the case of autoimmune disorders, they do not. The body’s immune system attacks healthy tissue.
Examples of autoimmune diseases include type-1 diabetes, rheumatoid arthritis, lupus, inflammatory bowel disease (IBD), psoriasis, and multiple sclerosis (MS). Due to medical cannabis’ and phytocannabinoids’ ability to dampen inflammatory responses, it has much potential to manage various autoimmune diseases.
What are Autoimmune Diseases?
Autoimmune diseases are where the human body’s immune system attacks a part or parts of its own body, including healthy tissue. As autoimmune diseases disrupt usual bodily functions, they are sometimes termed “autoimmune disorders.” Many autoimmune diseases are thought to start from a late infection of the Epstein-Barr Virus, the deficiency of CD8+ T-cells, and a predisposition towards a specific autoimmune condition on HLA class II genes.
Seven to eight percent of Americans (23-27 million) have an autoimmune disease. Due to women’s high-functioning immune system (which makes women more likely to be immune to or survive conditions like COVID-19), they are more likely to suffer from an autoimmune disease.
Common symptoms of autoimmune diseases include:
- Aching muscles.
- Swelling and redness.
- Low-grade fever.
- Difficulty concentrating.
- Numbness and tingling in the hands and feet.
- Hair loss.
- Skin rashes.
- In later stages of some autoimmune diseases, autoimmune-related encephalopathies (brain inflammation) and dementia.
Some autoimmune diseases affect just one body part (e.g., the myasthenia gravis, which attacks neuromuscular cells). In contrast, others affect multiple organs (e.g., systemic lupus erythematosus, which attacks joints, skin, kidneys, brain, heart, lungs, and blood cells). Conditions can either be autoimmune or not. These include multiple sclerosis (MS) and arthritis, which have autoimmune and non-autoimmune types.
Both genetic and environmental factors have a part to play in the development of an autoimmune disease, although it does seem that there are certain commonalities between them. For example, an abnormality in the same gene can cause Crohn’s disease or type 1 diabetes.
- Rheumatoid arthritis, where the immune system attacks the bones and joints.
- Hashimoto’s autoimmune thyroiditis, where the immune system attacks the thyroid gland and causes hypothyroidism (elevated thyroid-stimulating hormone, or TSH, and low free thyroxine, or T4, concentrations).
- Celiac disease, where the immune system attacks the small intestine when you eat gluten. It is considered an IBD, like Crohn’s and colitis.
- Graves’ disease, where the immune system attacks the thyroid and causes it to become overactive. Unlike Hashimoto’s, Graves’ is associated with hyperthyroidism (low TSH and elevated free T4 concentrations).
- Diabetes mellitus, type 1, where the immune system attacks and destroys insulin-producing cells in the pancreas. This leads to high blood sugar levels, damaging blood vessels, organs, and nerves. Neuropathic (nerve) pain is a typical result of type-1 diabetes.
- Vitiligo (aka leucoderma), where the immune system attacks the pigment in the skin, reducing melanin production and causing white patches on the skin. Stress and anxiety can trigger further loss of pigmentation.
- Rheumatic fever (aka acute rheumatic fever) where the immune system attacks and inflames the body’s heart, joints, brain, and skin. Rheumatic fever usually develops due to an overreaction to a strep throat or scarlet fever infection that hasn’t been fully treated.
- Pernicious anemia/atrophic gastritis, where the immune system attacks the cells in the stomach. Pernicious anemia is a decrease in red blood cells when the intestines cannot properly absorb vitamin B12. Atrophic gastritis is an inflammation and weakening of the stomach, and pernicious anemia can lead to atrophic gastritis.
- Alopecia areata, where the immune system attacks hair follicles, causing hair loss on any body part.
- Immune thrombocytopenic purpura, where the immune system attacks the platelets in the blood, can cause easy bruising, bleeding gums, and internal bleeding.
Other examples include Sjogren’s syndrome, Guillain-Barre syndrome, and psoriasis. Suffering from one autoimmune condition can increase the likelihood of developing another. Those with Lupus are more likely to suffer from rheumatoid arthritis, systemic sclerosis/scleroderma, and autoimmune hepatitis. Arthritis is also the most common extraintestinal complication of IBD.
Inflammation and immune system dysregulation (dysinflammation) is a key part of every autoimmune disease or disorder.
Brief Summary of Current Treatments
Exercise, dietary changes (e.g., gluten-free diets), probiotic and prebiotic therapies, and physical therapy are common non-drug treatments. Insulin injections may be necessary for type-1 diabetes.
Drug treatments include:
- Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, may reduce the cardiovascular risk of autoimmune/auto-inflammatory diseases (but increase cardiovascular risks in the general population).
- Corticosteroids such as prednisolone or fluticasone reduce inflammation and act as immunosuppressants.
- Analgesics such as acetaminophen (Tylenol, paracetamol) and codeine (an opioid-based painkiller) may be bought over the counter or prescribed to manage pain.
- Immunosuppressive drugs inhibit the activity of the immune system. Other than steroids, these include hydroxychloroquine (Plaquenil) and sulfasalazine (Azulfidine).
How Might Medical Cannabis Help?
The ECS plays a massive role in inflammatory responses and immune system regulation. In autoimmune disorders, the endocannabinoid system (ECS) is not functioning correctly. Phytocannabinoids may be of immense use for many different types of autoimmune conditions and help prevent the release of pro-inflammatory cytokines. Phytocannabinoids can help re-regulate the immune system and dampen inflammation.
Both THC and CBD inhibit interferon-gamma (IFN‐γ) secretion. IFN‐γ is a cytokine that plays a vital role in inducing and modulating an array of immune responses. Both cannabinoid receptor type 1 (CB1 or CB1R) and receptor type 2 (CB2 or CB2R) are promising targets for managing autoimmune diseases.
Many drugs currently prescribed for treating autoimmune diseases also have several adverse side effects. These include abdominal pain, GI upset, headaches, nausea, and rashes; In the case of codeine, addiction also. Medical cannabis has far fewer adverse side effects by comparison.
- Tetrahydrocannabinol (THC) acts as an anti-inflammatory and immunosuppressant, helping to calm an overactive immune response.
- Cannabidiol (CBD) “reduces the levels of pro-inflammatory cytokines, inhibits T cell proliferation, induces T cell apoptosis, and reduces migration and adhesion of immune cells.”
- Cannabigerol (CBG) may also suppress immune function and protect them from autoimmune encephalomyelitis (brain inflammation) in mouse models.
- Cannabinol (CBN) has sedative and anti-inflammatory effects that may help manage autoimmune disorders.
- Cannabichromene (CBC) is a CB2 receptor agonist that may help stem inflammation.
- Tetrahydrocannabivarin (THCV) has anti-inflammatory effects.
- The acidic cannabinoids, tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA) both have anti-inflammatory and pain-relieving effects.
- THC:CBD 1:3
- THC:CBD 1:2
- THC:CBD 1:1
- High THC ratios like 2:1 and 3:1 may also help manage pain.
Terpenes and Terpenoids
- Beta-caryophyllene could help relieve pain and inflammation via agonism of CB2 receptors in the immune system, helping decrease the release of inflammatory cytokines.
- Myrcene could help manage insomnia due to its sedative effects.
- Linalool may help due to its relaxing effects.
- Limonene could help lift the mood and manage anxiety and depression.
- Pinene has antidepressant, antioxidant and antibacterial properties.
- Terpinene has anti-inflammatory properties.
Flavonoids have many anti-inflammatory properties and are a promising source of new drugs for targeting autoimmune disease-related pain and inflammation. Some flavonoids of interest include:
Effective Ways of Taking Medical Cannabis for Autoimmune Diseases
Routes of Administration
A cannabis formulation or chemotype rich in THC, CBD, and beta-caryophyllene may be ideal. Other cannabinoids and terpenes like CBG, CBN cannabichromene (CBC), pinene, and linalool could also be helpful.
- Topical cream or salve
What are the Pros and Cons of Taking Medical Cannabis for Autoimmune Disorders?
Medical cannabis and its constituents could be beneficial for managing and possibly even treating various autoimmune diseases due to its immunomodulatory properties.
- Phytocannabinoids may be useful in helping to modulate the immune system and prevent the release of pro-inflammatory cytokines. Interestingly, this property also makes cannabinoids potentially helpful in treating cytokine storms and extreme inflammation associated with long COVID and the recovery stages of COVID-19.
- Phytocannabinoids mimic our bodies’ endocannabinoids and help regulate the immune system and prevent inflammation.
- “THC can change critical molecules of epigenome called histones, leading to suppression of inflammation.“
- This can depend on the autoimmune disease. THC may increase confusion and impact memory for some.
- For type 1 diabetes, cannabinoids like tetrahydrocannabivarin (THCV), CBG, and CBD may be useful but also cause complications such as higher caloric intake.
Useful Anecdotal Information
- ‘Medical Cannabis: What people with arthritis need to know’ | The Arthritis Society
- ‘The Science of Medical Cannabis for Arthritis’ – Jason J. McDougall (Ph.D.)
- Michele R. Berman, MD, and Mark S. Boguski, MD, Ph.D. “SNL Star Treats Crohn’s Disease with Marijuana.” MedPage Today, Dec. 6, 2018.
Scientific Data Overview and Studies
- Total Studies = 289 (Crohn’s, colitis, rheumatoid arthritis, myasthenia gravis, Graves’ disease, multiple sclerosis, diabetes mellitus, familial Mediterranean fever)
- Positive Studies = 259
- Inconclusive Studies = 25
- Negative Studies = 5
- 157 Meta-analyses (133 positive, 20 inconclusive, 4 negative); 73 animal studies (72 positive, 1 inconclusive); 21 double-blind human trials (18 positive, 3 inconclusive); 18 human trials (16 positive, 1 inconclusive, 1 negative); 20 lab studies (all positive)
- 102 studies include CBD (94 positive, 8 inconclusive); 90 studies include THC (82 positive, 8 inconclusive); 2 studies include CBC (both positive); 6 studies includes CBG (all positive); 2 studies includes CBN (both positive); 2 studies include THCV (both positive); 1 study include CBDA (positive); 2 studies includes THCA (both positive); 41 studies include a 1:1 THC:CBD ratio (all positive); 24 studies include the endocannabinoid, anandamide (all positive); 25 studies include the endocannabinoid, 2-arachidonoylglycerol (2-AG, 24 positive, 1 inconclusive)
- No. of Leafwell Patients (2021) = 244 (multiple sclerosis); 782 (inflammatory bowel disease); 485 (arthritis/rheumatoid arthritis)
- Possible Overall Efficacy: High
Quotes from Studies
“Medical uses of Cannabis sativa have been known for over 6,000 years. Nowadays, cannabis is mostly known for its psychotropic effects and its ability to relieve pain, even though there is evidence of cannabis use for autoimmune diseases like rheumatoid arthritis centuries ago. The pharmacological therapy in autoimmune diseases is mainly based on immunosuppression of different axes of the immune system while many of the drugs have major side effects. In this review we set out to examine the rule of Cannabis sativa as an immunomodulator and its potential as a new treatment option. In order to examine this subject we will focus on some major autoimmune diseases such as diabetes type I and rheumatoid arthritis.” Source: Katz D, Katz I, Golan A. ‘[MEDICAL CANNABIS – A SOURCE FOR A NEW TREATMENT FOR AUTOIMMUNE DISEASE?].’ Harefuah. 2016 Feb;155(2):74-8, 133. Hebrew. PMID: 27215114.
“The activities of the large number of compounds contained in whole cannabis plants is extremely complex because the compounds themselves not only bind to a plethora of different receptors but also interact with each other both synergistically and otherwise:42 for example, pinene is an acetylcholinesterase inhibitor that may decrease the short-term memory impairment induced by THC.16 What follows is a brief summary of the activity of other PCs and terpenes (which have been more extensively reviewed elsewhere).43
CBG is an AEA reuptake inhibitor which, when combined with CBD, has anti-inflammatory activity as it reduces the expression of tumour necrosis factor (TNF) and up-regulates interleukin (IL)-10 and IL-37 levels.44 CBC is also an agonist of CB receptor 2,45 and CBN inhibits COX, LOX, and P450 cytochrome enzymes.
Terpenes are very promising compounds as they have a variety of positive (analgesic, anti-depressant, anti-oxidant, and anti-bacterial) functions,42 but the possible contribution of adding terpenoids to cannabinoids is uncertain.43 It has been reported that caryophyllenes are anti-microbial, anti-proliferative, anti-fungal, anti-oxidant and anti-inflammatory acetylcholinesterase inhibitors;46 D-limonene may be anti-inflammatory as it mediates the inhibition of pro-inflammatory mediators, leukocyte migration, and vascular permeability.47 Gamma-terpinene has an effect on the pro- and anti-inflammatory macrophage production of cytokines, particularly through the IL-10 axis.48”
Source: Giorgi V, Marotto D, Batticciotto A, Atzeni F, Bongiovanni S, Sarzi-Puttini P. “Cannabis and Autoimmunity: Possible Mechanisms of Action.” Immunotargets Ther. 2021;10:261-271. Published Jul. 21 2021. doi:10.2147/ITT.S267905
There is a high level of evidence to suggest that medical cannabis and various phytocannabinoids, terpenes, and flavonoids could help manage symptoms and reduce inflammation associated with many different autoimmune diseases.
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