Fall 2020

Cannabis for Autoimmune Disorders

Alternative treatments are needed for these puzzling conditions that aren’t well addressed by conventional medicine. Can cannabis help?

With more than 80 documented autoimmune disorders affecting upwards of 24 million people in America today, health care professionals are tasked with treating the often debilitating and unrelenting symptoms of patients with vague and complex diagnoses of disorders that are often incurable.1 It’s no wonder patients and clinicians alike are desperately seeking alternative treatment options.

As the prevalence of autoimmunity continues to rise, so does the amount of anecdotal evidence from patients reporting both medicinal and recreational cannabis use to positively manage their symptoms of autoimmune disease. With rapid progress being made in the understanding of cannabinoids and how they interact with cannabinoid receptors in the immune system, more and more clinical evidence supports the theory that the endocannabinoid system (ECS) plays a much more important role in immunity than previously believed.

Considering autoimmunity as an overreaction of the immune system targeting healthy cells in the body, it’s logical to think the ECS might play a key role in symptom management and even remission of autoimmune disease. The ECS is a complex system of messengers, cannabinoid receptors, and related enzymes that’s believed to have a profound influence over the immune and other body systems and physiological processes.2 Endocannabinoids are believed to control immune functions and play a role in immune homeostasis.

While no two autoimmune conditions present in the same way, there’s great promise that cannabis may hold answer to the complex and often frustrating autoimmunity puzzle. To understand how cannabis may help with autoimmune disorders including arthritis, type 1 diabetes, and psoriasis, it’s necessary to understand the ECS, specifically the CB2 receptor and the role it plays in autoimmunity, and explore the evidence.

Autoimmunity and the ECS
The ECS—the broad purpose of which is to maintain homeostasis within the body—is made up of three major components: messengers, receptors, and enzymes. There are two primary cannabinoid receptors, the CB1 receptors found in the brain and central nervous system, and the CB2 receptors found primarily on immune cells. The ECS is an important modulator of the immune system and is influenced by a patient’s cannabis use.

Evidence supports cannabis and its active ingredients as “immune-modulating agents, affecting T cells, B cells, monocytes, and microglia cells, causing an overall reduction in proinflammatory cytokine expression and an increase in anti-inflammatory cytokines.”3

In the ECS, the majority of CB2 receptors are located in the immune system, suggesting that cannabinoids may play an important role in modulating the immune response. When exogenous cannabinoids such as CBD or THC are introduced to the body through external cannabis use, they exert an autoimmune effect by modulating neurotransmitter and cytokine release while additionally possessing immunosuppressive properties through apoptosis.4,5

It’s believed that, along with immunosuppression, the ECS is also involved in immunoregulation, making the ECS a viable target for research that explores whether immunoregulation, rather than immunosuppression, is better for the prevention and treatment of autoimmune disorders.

Immunity and CB2 Receptors
Various tissues in the body can contain both CB1 and CB2 cannabinoid receptors, although each receptor is believed to be linked to a different action. CB2 receptors are found mostly in the peripheral tissues of the body, including the immune system. It’s thought that CB2 receptors are a mediator for suppressing pain and inflammation and have therapeutic potential in inflammatory, fibrotic, and neurodegenerative diseases.6

While the relationship between CB2 receptors and the immune system has yet to be fully defined, CB2 receptors activate the immunomodulatory effects of endocannabinoids and signal the immune system as needed. This makes them of particular interest for the development of a therapeutic treatment for autoimmune conditions due to their location, their mode of action, and their inability to cause intoxicating affects, unlike CB1 receptors.7

The most common forms of autoimmune arthritis are rheumatoid arthritis and psoriatic arthritis. In both cases, clinical manifestation is characterized by joint pain, stiffness, lack of coordination, and loss of abilities, all of which significantly decrease quality of life. Increasing evidence supports the theory that the ECS participates in the pathophysiology of arthritis-associated joint pain, suggesting that cannabinoid therapy may provide therapeutic relief for these autoimmune conditions.8

Patients with chronic arthritic and musculoskeletal pain are the most prevalent users of therapeutic cannabis products. This suggests that the clinical evidence is just starting to catch up to the longstanding anecdotal reports that cannabis helps relieve autoimmune-driven arthritis pain. Arthritis remains a qualifying condition for medical cannabis programs across the country, including psoriatic arthritis in Connecticut and rheumatoid arthritis in Hawaii.

Beyond medical cannabis, legal and easily accessed CBD products are quickly gaining popularity among many arthritis patients. Through its combined immunosuppressive and anti-inflammatory actions, CBD has demonstrated a potent antiarthritic effect in animal studies. One study published in Proceedings of the National Academy of Sciences supports the therapeutic potential of the sublingual use of CBD for arthritic conditions, with an optimal effect being seen at 25 mg of CBD per kilogram of body weight.9

CBD is popular among patients with arthritis, and clinicians should be aware that medical cannabis may bring relief to many. As with all patients, it is best to encourage an open and honest discussion about all topical and/or ingested cannabis products patients with arthritis may be using. Additionally, further research is needed about CBD’s immunomodulatory role in rheumatoid and psoriatic arthritis.

Type 1 Diabetes
Type 1 diabetes, an autoimmune condition characterized by a lack of insulin production that occurs when the body attacks otherwise healthy pancreatic cells. While there’s not enough clinical evidence to directly connect cannabinoids to diabetes management, researchers are interested in the potential of cannabinoid therapeutics for this autoimmune disorder.

Studies aiming to explore the link between diabetes and the ECS have led to an understanding of the role that CB2 receptors play in insulin secretion by facilitating calcium entry into pancreatic beta cells. These findings suggest the potential important role of CB2 receptor activation in the management of diabetes. CB2 receptor agonist drugs are being studied for their possible role in the reduction of
glucose levels, production of insulin levels, and decrease in the hyperglycemic oxidative stress and inflammation.10

One of the most painful side effects of both type 1 and type 2 diabetes is neuropathic pain. In different experimental animal models, cannabinoids have been found to relieve the symptoms associated with diabetic neuropathy. Rat studies suggest that cannabinoids “may serve as a new therapeutic alternative for symptom management in painful neuropathy associated with both type 1 and type 2 diabetes.”11

CBD specifically has shown promise in one animal study for reducing early pancreatic inflammation in type 1 diabetes. Preliminary evidence suggests that mice treated with CBD at 5 mg/kg of bodyweight had reduced markers of inflammation and a significant delay in the development of type 1 diabetes.12

Additionally, existing studies suggest that cannabis use may have an adverse effect on glycemic management. However, it’s not clear if those are related to the cannabis use itself or to other factors such as youth. While the research on type 1 diabetes and cannabis use is still emerging, it’s important to have conversations about cannabis use with your patients with type 1 diabetes, especially juveniles. Glycemic management is difficult enough, especially for the newly diagnosed, and the addition of cannabis into the equation can complicate that.

Psoriasis is a chronic autoimmune condition characterized by skin cell build-up that forms itchy dry patches and scales. Persistent rashes on the skin, often on the knees or elbows, are itchy, painful, and sometimes embarrassing. Chronic psoriasis can last for years or even a lifetime, significantly reducing the quality of life for the patient. Psoriasis is characterized by both autoimmune and autoinflammatory processes, and there’s no cure, making cannabinoid therapeutics an intervention of significant interest.13

Cannabinoid therapy is being explored in the field of dermatology, where already there are several approved medical indications for cannabis use, including psoriasis, lupus, nail-patella syndrome, and severe pain.13 Researchers believe that beyond the ECS is a cutaneous cannabinoid system called the c[ut]annabinoid. They believe this system is responsible for maintaining skin homeostasis, helps create barriers, induces regeneration, and is directly connected to several diseases and disorders including “atopic dermatitis, psoriasis, scleroderma, acne, hair growth and pigmentation disorders, keratin diseases, various tumors, and itch.”14

Several studies have examined the use of cannabinoids for autoimmune psoriasis specifically, with one claiming that cannabinoid treatment for psoriasis has significant potential due to its ability to “suppress the two main steps of psoriatic pathogenesis.”15

Psoriasis is a qualifying condition for some but not all medical cannabis programs. Again, it’s important for health care practitioners to have open discussions with their patients, especially if they’re using any type of cannabinoid product to treat their psoriasis, either topically or internally.

Could Autoimmunity, CECD Be Related?
When treating patients who have one or more autoimmune disorders, clinicians should keep in mind the theory of clinical endocannabinoid deficiency (CECD). Just as patient-centered care maintains that no two patients should be treated in the same way, clinicians must understand that no two ECSs can be treated in the same way. The ECS varies widely from person to person, with each person having a unique endocannabinoid tone—a phrase coined by Ethan Russo, MD, a leading expert in the system. It’s believed that many physiological and external factors can affect an individual’s endocannabinoid tone. When the tone becomes deficient, CECD may occur.16

Russo proposes a theory, supported by emerging evidence, that an underlying endocannabinoid deficiency may be the root of several conditions, including some autoimmune conditions. The greatest evidence supports that the endocannabinoid deficiency is the center of development for the most vague and complicated conditions including migraine, fibromyalgia, and irritable bowel syndrome. Clinical data have provided evidence for the beneficial use of cannabinoid treatment and adjunctive lifestyle approaches affecting the ECS in individuals with suspected CECD, resulting in decreased pain and improved sleep, along with other benefits.17

Understanding that CECD may be treated with either medical or adult use cannabis is important for health care providers who work with patients who use or are considering using cannabis to manage the symptoms of their autoimmune diseases. With an understanding of the system and the ways in which cannabis may be beneficial, you may be able to guide your patients in trialing various cannabinoid ratios, application methods, and dosages until together you find a viable solution that provides optimal pain and symptom relief.

— Emily Kyle, MS, RDN, CDN, CLT, HCP, is a registered dietitian nutritionist and certified holistic cannabis practitioner. As a three-time published cookbook author, she combines the medicinal, nutritional, and culinary aspects of cannabis use through the creation of detailed cannabis-infused recipes. She advocates for responsible adult-recreational cannabis use and shares her published resources at and on Instagram at @EmilyKyleNutrition.


1. Autoimmune diseases. National Institute of Environmental Health Sciences website. Updated May 6, 2020. Accessed June 1, 2020.

2. Rodríguez de Fonseca F, Del Arco I, Bermudez-Silva FJ, Bilbao A, Cippitelli A, Navarro M. The endocannabinoid system: physiology and pharmacology. Alcohol Alcohol. 2005;40(1):2-14.

3. Katz D, Katz I, Porat-Katz BS, Shoenfeld Y. Medical cannabis: another piece in the mosaic of autoimmunity? Clin Pharmacol Ther. 2017;101(2):230-238.

4. Nagarkatti P, Pandey R, Rieder SA, Hegde VL, Nagarkatti M. Cannabinoids as novel anti-inflammatory drugs. Future Med Chem. 2009;1(7):1333-1349.

5. Kotchan V, David P, Shoenfeld Y. Cannabinoids and autoimmune diseases: a systematic review. Autoimmun Rev. 2016;15(6):513-528.

6. Li X, Hua T, Vemuri K, et al. Crystal structure of the human cannabinoid receptor CB2. Cell. 2019;176(3):459-467.e13.

7. Pandey R, Mousawy K, Nagarkatti M, Nagarkatti P. Endocannabinoids and immune regulation. Pharmacol Res. 2009;60(2):85-92.

8. Bruni N, Della Pepa C, Oliaro-Bosso S, Pessione E, Gastaldi D, Dosio F. Cannabinoid delivery systems for pain and inflammation treatment. Molecules. 2018;23(10):2478.

9. Malfait AM, Gallily R, Sumariwalla PF, et al. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci U S A. 2000;97(17):9561-9566.

10. Kumawat VS, Kaur G. Therapeutic potential of cannabinoid receptor 2 in the treatment of diabetes mellitus and its complications. Eur J Pharmacol. 2019;862:172628.

11. Vera G, López-Miranda V, Herradón E, Martín MI, Abalo R. Characterization of cannabinoid-induced relief of neuropathic pain in rat models of type 1 and type 2 diabetes. Pharmacol Biochem Behav. 2012;102(2):335-343.

12. Lehmann C, Fisher NB, Tugwell B, Szczesniak A, Kelly M, Zhou J. Experimental cannabidiol treatment reduces early pancreatic inflammation in type 1 diabetes. Clin Hemorheol Microcirc. 2016;64(4):655-662.

13. Liang Y, Sarkar MK, Tsoi LC, Gudjonsson JE. Psoriasis: a mixed autoimmune and autoinflammatory disease. Curr Opin Immunol. 2017;49:1-8.

14. Dhadwal G, Kirchhof MG. The risks and benefits of cannabis in the dermatology clinic. J Cutan Med Surg. 2018;22(2):194-199.

15. Norooznezhad AH, Norooznezhad F. Cannabinoids: possible agents for treatment of psoriasis via suppression of angiogenesis and inflammation. Med Hypotheses. 2017;99:15-18.

16. Russo EB. Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinol Lett. 2008;29(2):192-200.

17. Russo EB. Clinical endocannabinoid deficiency reconsidered: current research supports the theory in migraine, fibromyalgia, irritable bowel, and other treatment-resistant syndromes. Cannabis Cannabinoid Res. 2016;1(1):154-165.


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