Cannabis for Autoimmune Disease: Benefits Beyond Symptom Relief?

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Since autoimmune disease involves malfunction of the immune system, the same research on cannabis and immune system disorders applies to autoimmune disease. And as with more traditional treatments for autoimmune disease, cannabis tends to address immune system disorders by decreasing inflammation and swelling.

Autoimmune disorders occur when our immune systems malfunction. To understand autoimmune disorders, we must, therefore, first understand how the immune system works.

Our immune systems are responsible for protecting our bodies from anything harmful, whether coming from outside our bodies or from within. To do this, our immune systems must be able to distinguish between self and non-self. An 

 is any molecule that our immune systems recognize as being non-self. Our bodies are pre-programmed to recognize thousands of different antigens, and they also learn to designate additional molecules as antigens based on experience. When our immune system identifies a molecule in our body as an antigen, it tags it with a unique identifier called an 

. The antibody signals to the rest of the immune system that the antigen is a non-self-molecule, so it can be destroyed (1). The presence of antibodies tagged to antigens triggers a response by our immune systems, which generates white blood cells (“lymphocytes”) of varying types to kill the antigens and remove them from our bodies (2).

 is an immune system response to the presence of viruses, bacteria, injuries, or other sources that damage our cells. During the inflammation process, blood vessels dilate and become permeable, enabling white blood cells and other harm-fighting agents to flow to the area of injury. The dilated blood vessels cause heat and redness, the flood of white blood cells into the area causes swelling, and other immune system agents increase sensitivity to pain. Once the pathogens have been neutralized, our immune systems clean up the debris then repair any damage, restoring our bodies to normal (3).

Autoimmune disease occurs when the body mistakes self for non-self: our immune systems mistake specific molecules from our own body’s organs and tissues as being toxic antigens. Our immune systems then respond accordingly, by tagging the antigens with antibodies and mounting attacks on those cells. Since the molecules mistaken for toxic antigens are generated by normal–that is, ongoing–bodily functions, the attacks by our immune systems on our own cells becomes a persistent process (4).

Autoimmune disease is not well-understood by the medical community. It is thought to involve both genes and environment. Specifically, genetic and environmental phenomena increase the reactivity of our immune systems, making it easier for our bodies to mistake benign molecules for toxins (4).

Autoimmune disease occurs in about 3-6% of the population; it is more common in females and specific forms of the disease are more common in particular ethnic groups. Since the incidence of autoimmune disease has been increasing, it suggests environmental factors, including overexposure to chemicals, a Western diet, or underexposure to germs (that is, excessively antiseptic environments), contribute to its development (5).

Common forms of autoimmune disease include, for example (5):

Rheumatoid arthritis (RA): The immune system attacks joints, causing joint soreness and stiffness.

Multiple sclerosis (MS): The immune system attacks the insulation (that is, myelin sheath) that protects nerve fibers and enables the smooth flow of signaling between the brain, spinal cord, and the rest of the body.

Inflammatory bowel disease (IBD): The immune system attacks the lining of the intestinal wall, causing digestive problems.

Essentially, autoimmune disease involves hyperactivity of the immune system. This hyperactivity causes two sets of problems. First, as the immune system attacks cells from a patient’s own body, it causes damage to the affected areas. The direct damage then causes problems with interconnected activities. For example, in the case of multiple sclerosis, the immune system attacks myelin sheaths on nerve fibers. This impedes signaling between the brain, spinal cord, and the rest of the body, leading to problems such as limb numbness, tremors, and pain.

The second set of problems caused by autoimmune disease is collateral damage to nearby cells and tissues associated with the ongoing swelling and irritation of the immune system.

There are no cures for autoimmune disease. There are, however, treatments that focus on reducing immune system activity (that is, immunosuppressants), such as painkillers, anti-inflammatories, cortisone pills, and creams (5).

Research on Cannabis and Autoimmune Disease

Since autoimmune disease involves malfunction of the immune system, the same research on cannabis and immune system disorders applies to autoimmune disease. As with more traditional treatments for autoimmune disease, cannabis tends to address immune system disorders by decreasing inflammation and swelling.

 studies examining how cannabis works to treat the symptoms and causes of autoimmune disease.

Let’s start with cannabis’s mechanisms of actions (MoAs) for autoimmune disease generally. The primary way cannabinoids influence cells is by binding to receptors that are located on cell surfaces, thereby inducing activity. Cannabinoid type 2 receptors (CB2) are densely located on all different types of immune system cells. Generally speaking, then, cannabis helps treat autoimmune disorders by binding to cannabinoid receptors on immune system cells, causing decreases in immune system activity. Four immunosuppressive mechanisms of action in particular enable cannabis to relieve symptoms from autoimmune disorders.

Induce cell death: Apoptosis is a natural process used by the body to rid itself of unneeded or abnormal cells. Cannabinoids induce apoptosis in white blood cells involved in the inflammation process (that is, killer T cells), thus alleviating the inflammatory response (6-8).

Inhibit cell proliferation: Cell proliferation is the speed at which cells replicate themselves. Cannabinoids inhibit cell proliferation in white blood cells involved in the inflammation process (that is, killer T cells, B cells), thus alleviating the inflammatory response (6-9).

Suppress cytokine production: Cytokines are part of the entourage of immune system cells; one of their functions is to help either amplify or limit inflammatory responses. Autoimmune disease may cause malfunctions in the immune system that cause long-term production of pro-inflammatory cytokines (7). Cannabinoids suppress cytokine production, thus alleviating the inflammatory response (6,7,9,10).

Induce regulatory T cell production: Finally, cannabinoids induce production of white blood cells that suppress the cytokine production (that is, regulatory T cells), thus mitigating inflammatory responses associated with autoimmune disease (7,8,11).

Aside from addressing general autoimmune dysfunction, studies have also established cannabis’s MoAs for addressing specific autoimmune diseases.

Crohn’s disease and IBD: Studies have shown that the endocannabinoid system regulates intestinal inflammation (6) and intestinal motility (movement of substances through the gastrointestinal tract) (12).

Multiple sclerosis: Studies have shown that cannabis may inhibit the inflammatory response in MS that contributes to the destruction of myelin and myelin-producing cells. By inhibiting these inflammatory responses, cannabis mitigates MS-induced bladder control problems, pain, spasticity, and tremors (13).

Rheumatoid arthritis: Studies have shown that cannabis inhibits progression and proliferation of RA generally by inducing cell death that reduces bone tissue degeneration (7). Studies have also shown that cannabinoid receptors are located in the synovia, that is the fluid-filled cavities, which keep bones together and permit free bone movement. In the synovia, cannabinoids prevent the progression of RA by reducing synovial inflammation and bone destruction (6).

One large-scale retrospective study of patients with Crohn’s Disease (14) and several other much smaller studies concluded that patients found substantial improvements in their symptoms after using cannabis.

MS is one of the most-studied diseases for cannabis treatment. Dozens of clinical studies, including a good number of moderately-sized randomized controlled trials, have found that cannabis may improve MS-related bladder control problems, pain, spasticity, and tremor.

“There are currently no randomized clinical trials investigating the use of cannabis in the treatment of RA, partly because of the availability of effective biological anti-inflammatory agents in the therapeutic armamentarium. However, one preliminary randomized, placebo-controlled study has assessed the efficacy, tolerability and safety of five weeks’ treatment with a synthetic tetrahydrocannabinol (THC) analogue in 58 RA patients and found that pain was significantly reduced and disease activity significantly suppressed” (6).

Several issues noted by researchers about cannabis and autoimmune disease are worth mentioning.

Cannabis Treatment for Autoimmune Disease Must Be Personalized

“As each autoimmune disease differ [sic] in symptoms, it also differs in the ‘culpable’ immune cells and cytokines inciting the disease. Hence, declaring that cannabis treatment is beneficial for autoimmune diseases does not suffice, and treatment options should be tailored for each disease.” Furthermore, since each person’s body chemistry and endocannabinoid system are unique, “cannabis or cannabinoid treatment should possibly be tailored not only per disease but also per person,” (6).

, that is, low doses can generate one effect in patients while higher doses exhibit the opposite effect. For example, studies have shown that low doses of THC may decrease anxiety, while higher doses may increase anxiety (15).

These same biphasic effects have been found for cannabis’s effects on the production of white blood cells: low doses of cannabinoids may stimulate the production of white blood cells (T cells, B cells, and cytokines), while higher doses may decrease production (7-9).

Promotes Infection by Suppressing the Immune System

The discussion thus far has noted the ability of cannabis to suppresses immune system activity. This suppression helps reduce hyperactive immune systems in patients with autoimmune disease, thereby providing relief. At the same time, however, we must recognize that a primary role of the immune system is to fight off infections. In this sense, then, using cannabis to suppress immune system activity to help with autoimmune disease may inadvertently increase patients’ susceptibility to infections (8).

http://www.scienceclarified.com/Al-As/Antibody-and-Antigen.html

https://www.news-medical.net/life-sciences/What-is-an-Ant?”igen.aspx

https://medlineplus.gov/ency/article/000821.htm

P. Marrack, J. Kappler, and B.L. Kotzin, 

https://www.healthline.com/health/autoimmune-disorders

V. Giorgi, D. Marotto, A. Batticciotto, F. Atzeni, S. Bongiovanni, and P. Sarzi-Puttini, 

P. Nagarkatti, R. Pandey, S.A. Rieder, V.L. Hegde, and M. Nagarkatti, 

https://pubmed.ncbi.nlm.nih.gov/26876387/

https://pubmed.ncbi.nlm.nih.gov/16918439/

https://www.abcam.com/research-areas/cytokines-and-inflammation

https://www.frontiersin.org/articles/10.3389/fimmu.2017.01487/full

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783846/

Current Drug Targets - CNS & Neurological Disorders

https://www.researchgate.net/publication/7394957

https://link.springer.com/article/10.1007/s10620-019-05556-z

https://pubmed.ncbi.nlm.nih.gov/33008420/

, 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.

In this article, Ruth Fisher, PhD, presents some of the research being explored with cannabis and autoimmune disorders.


Research Overview:  Cannabis and Autoimmune Disorders

Autoimmune diseases often cause pain, inflammation, spasticity, itching, and gastrointestinal distress. Cannabis, well known for its analgesic, anti-inflammatory, antispasmodic, antipruritic (anti-itch), and gut-balancing effects, often works well for improving symptoms in people with autoimmune conditions. But can cannabis impact the underlying disturbance leading to these symptoms? This article reviews the clinical evidence examining the efficacy of cannabis in the treatment of common autoimmune conditions and takes a deeper look at the preclinical evidence suggesting that cannabis may be able to modify the autoimmune disease process. At the end of the article, I provide tips for implementing cannabis-based therapies in individuals with autoimmune diseases.

What Is Autoimmune Disease and Why Does It Occur?

Inflammation is a normal physiological defense against infection and tissue damage; it serves its role in the healing process and quickly ends, under normal circumstances. Sometimes, however, the immune system becomes dysregulated, and inflammation persists, causing tissue and organ damage. In autoimmune diseases, inflammatory symptoms persist because one’s immune system attacks targets on otherwise healthy human cells. More than 80 conditions have been categorized as autoimmune, and the symptoms vary widely depending on the tissue or organ targeted by the aberrant immune activity.

There is no single cause of autoimmune diseases; most occur at the intersection of genetics and environment. For example, many autoimmune conditions run in families, but not in a clear pattern of genetic inheritance, and identical twins rarely manifest the same autoimmune disease (1). This suggests a genetic predisposition to autoimmune diseases, but environmental factors play a major role: microbial or viral infections, vaccinations (2), or major life stressors often precede autoimmune disorders.

Autoimmune conditions occur in about 8% of the population. The most common include type 1 diabetes, inflammatory bowel disease (Crohn’s disease and ulcerative colitis), thyroid disease (Hashimoto’s thyroiditis and Grave’s disease), multiple sclerosis, rheumatoid arthritis, Sjögren disease, psoriasis, and lupus—among many others. Though not consistent among all autoimmune diseases, many individuals with one have a higher likelihood of developing a second autoimmune condition (3).

Many patients with autoimmune diseases are told that their immune system has become confused and is now attacking healthy tissue, but until recently the mechanisms of that confusion have been poorly understood. Recent research suggests molecular mimicry is one of the leading mechanisms by which infectious or chemical agents may induce autoimmunity. It occurs when the T or B cells of the immune system react to a foreign antigen with a similar molecular structure to peptides normally found in human cells. Under certain conditions such as genetic predisposition or psychological stress, the antibodies or T cells will continue to react to the human tissues long after the infection or foreign chemical is gone. Other immune malfunctions, such as impaired immune tolerance, likely also play a role (4).

Some autoimmune diseases impact specific organs, causing related problems and their downstream symptoms; for example, diabetes attacks the pancreas and results in loss of insulin production, which causes high blood sugar, which, without careful management, causes a host of other problems; and Hashimoto’s attacks the thyroid gland and results in loss of thyroid hormone production. When the immune system attacks the musculoskeletal system or the skin, symptoms usually include swelling, pain, and itching. When the immune system attacks the nervous system, symptoms often include spasticity, weakness, sensory disturbances, and psychiatric symptoms.

During the 13 years in which I’ve treated patients with cannabis, I’ve witnessed hundreds of people with autoimmune diseases report improvement in symptoms and quality of life when using this versatile medicine. But that’s not unexpected, as I could say the same about many categories of diseases. Why is cannabis so broadly effective across such wide variety of conditions? The main reason is its capacity to interact with the endocannabinoid system (ECS), a master regulator of the other bodily systems, including the immune system. Other reasons include non-ECS targets of compounds found in cannabis that also modulate inflammation, metabolism, nerve function, and more.

One of the most common autoimmune diseases I’ve treated with cannabis, multiple sclerosis (MS), is also one of the best studied. Nabiximols (brand name Sativex), a pharmaceutical oral spray containing plant-derived tetrahydrocannabinol (THC) and cannabidiol (CBD), has been extensively investigated in randomized, controlled trials: between 2000 and 2010, nabiximols trials included more than 2500 patients with MS, of whom more than 660 were treated continuously for at least 6 months. Nabiximols was approved in several countries for the treatment of MS spasticity, and vast clinical experience with nabiximols in the post-marketing setting accounts for more than 150,000 patient-years of use to date. A recent review of the post-marketing data concluded that (5), “nabiximols is a solid option for the management of MS spasticity in patients who fail to respond adequately to treatment with first-line anti-spasticity agents.” The authors also noted that (5), “nabiximols can provide noticeable relief of other symptoms associated with spasticity such as spasms, pain and disrupted sleep.”

It has always bothered me when researchers and medical authorities ascribe cannabis to the category of second-line therapies, considering it has a superior safety profile compared to most first-line agents, an extensive list of side benefits typically conveyed to patients, and as described below, the potential to beneficially impact the underlying cause of the condition. In my practice, cannabis is appropriately used as a first-line agent for spasticity and pain when patients come to me early enough in their health journey.

The American Academy of Neurology, in a 2014 review of 34 studies, supported the use of oral cannabinoids in the treatment of MS spasticity, pain originating in the central nervous system, and spasticity-related pain, and found that oral cannabinoids are probably also effective for reducing bladder complaints in patients with MS (6). The data supporting oral use is substantial and the benefits are moderate, but not impressive.

While majority of the data on cannabis for MS comes from trials using oral cannabinoids, in my clinical experience, I have found inhaled cannabis to be much more effective for producing improvements in spasticity. One placebo-controlled crossover trial on 30 patients with MS using low-quality cannabis cigarettes (4% Δ

- tetrahydrocannabinol [THC]) versus placebo cigarettes smoked once daily for 3 days confirmed my observations: reductions in objective measures of spasticity were greater than those observed in the oral cannabis trials, and subjects also experienced more significant reductions in pain (7).

Very little clinical trial data on the effects of cannabis for other specific autoimmune conditions is available, though plenty of data supports the use of cannabis to treat symptoms such as pain and itching. Readers of this publication didn’t need the 2017 National Academies of Sciences, Engineering, and Medicine report to tell us that they found conclusive evidence that cannabis could effectively treat chronic pain (8)—pain is the most common reason people use cannabis for therapeutic purposes (9), and with or without placebo-controlled trials, they probably wouldn’t be doing so if it wasn’t helping.

It’s important to note that without cannabis as a first-line or even second-line treatment for pain in people with autoimmune conditions, opioids are often the only effective option. One study found that 40% of patients with rheumatoid arthritis used prescription opioids regularly (10). The consequences of long-term opioid use, including increased sensitivity to pain, hormone disruption, disturbed sleep, problematic use, and overdose, are finally common knowledge among clinicians and patients alike. While cannabis has been shown again and again to work as a tool for helping patients decrease and discontinue opioids, it’s even better when it’s used to avoid the need to start opioids in the first place.

Less commonly known, however, are the benefits of cannabis for treating pruritis (itching), a common manifestation of autoimmune conditions in the skin. Substantial preclinical evidence indicates the cannabinoids work via CB1 and CB2 receptors in itch-related nerves fibers in the skin to suppress signaling and via CB1 receptors in the spinal cord and brain to decrease the intensity of the sensation. Human clinical studies in a variety of skin conditions, including psoriasis and eczema, have consistently shown significant reductions in itching and scratching using both topical and systemic cannabinoid treatments (11). Not surprisingly, the topical treatments also resulted in decreased signs of inflammation.

Crohn’s disease and ulcerative colitis, collectively known as inflammatory bowel disease (IBD), are autoimmune diseases that affect the gastrointestinal tract. People with IBD experience both gastrointestinal symptoms like abdominal pain, diarrhea, bleeding, and weight loss, as well as systemic symptoms like joint pain and fatigue. Symptoms can be present daily but typically cycle through “flares” of exacerbation. The goal of treatment is not only to address symptoms, but also to prevent the need for surgical removal of the intestines and other complications including nutrient deficiencies and weight loss, anemia, fistulas, and more.

Little high-quality human research has examined the impact of cannabis in these conditions, and the studies that have been performed, in my opinion, have not used practical cannabis dosing strategies—low dose CBD isn’t going to cut it (12). Surveys of patients with these conditions, however, confirm what I’ve observed in my clinical practice: most patients with IBD who try cannabis, find it helpful and continue to use it. A survey of US patients with IBD found that 80% of those who tried cannabis reported benefits in their condition. Interestingly, 21% of those living in states with both medical and adult-use cannabis laws used adult-use products specifically for IBD without their clinician’s knowledge. The most commonly reported benefits (13) were related to pain (68%), appetite (49%), anxiety (48%), fatigue (26%), stool frequency (23%), weight gain (20%), and blood in stool (5%).

In a large, recent survey of people with IBD in Australia (14), 25% of respondents had used cannabis for their condition, and 93% of them endorsed cannabis as effective in symptom management. The most common symptoms helped by cannabis were abdominal pain, stress, sleep issues, cramping, anxiety, bloating, depression, reduced appetite, and diarrhea—amongst many others. The authors noted, “the magnitude of self-reported symptom improvement in the present survey was surprisingly high. Symptom improvements of the magnitude reported in this study are rarely seen in any therapeutic intervention.”

For symptomatic treatment, cannabis often sounds too good to be true. When asked if cannabis can help with—fill in the blank: pain, itching, stiffness, spasms, redness, hypersensitivity, diarrhea, cramping, anxiety, fatigue, insomnia, anxiety, and so forth—the answer is yes, in most people. Of course, not everyone responds to cannabis, and in some, the results are modest. In others, the benefits are profound, life-changing, and often allow patients to discontinue other treatments that have significant side effects. While treating symptoms is important, preventing them may be even more helpful for people with these conditions.

Anyone with an autoimmune disease will confirm that psychological stress plays a major role in their symptoms, and that high stress events can trigger a flare-up or even a relapse of their condition. Most clinicians who treat patients with autoimmune diseases will confirm that they see more flare-ups during times of major stress. It’s well-known that stress impacts the function of the immune system, but the association of stress and stress-reduction techniques with symptom severity in autoimmune diseases has not yet received substantial attention of researchers in the field, and seldom receives the attention of clinicians caring for these patients. In one study of 92 patients with rheumatoid arthritis, psychologic stress was reported to be the most common reason for disease flares (15).

As mentioned above, psychological stress is also implicated in the development of autoimmune diseases. A recent retrospective Swedish cohort study compared the incidence of autoimmune disease in more than 100,000 people with stress-related disorders such as post-traumatic stress disorder (PTSD), adjustment disorder, and acute stress reaction with the incidence of autoimmune disease in more than 126,000 of their full siblings and over 1 million matched control subjects without a stress-related disorder. During an average follow-up of 10 years after the stress-related disorder was diagnosed, and after controlling for confounding factors, the risk of developing an autoimmune disease was 36% higher in those with the stress-related disorder. Some conditions, such as autoimmune thyroid disease, had a stronger association with stress-related disorders, while rheumatoid arthritis was still increased in those with stress-related disorders but not as much as the other autoimmune conditions studied (16).

Why might severe life stress predispose individuals to the development of autoimmune disease? At a biological level, activation of the sympathetic (fight or flight) nervous system and increased levels of the stress hormone cortisol can impair immune function, potentially increasing susceptibility to and preventing recovery from infections that could trigger autoimmune disease. In patients with PTSD and other types of chronic stress, particularly related to early life trauma, “adrenal burnout” or chronically low cortisol levels can lead to over-activation of the immune system and increased levels of inflammatory cellular signals. Severe life stress also indirectly influences the risk for autoimmune disease via lifestyle factors such as sleep disruption, alcohol or substance abuse, and increased smoking.

Metaphorically, severe stress is usually related to the perception of uncontrollable threatening elements in one’s external environment, or the absence of a safe personal environment. This is reflected in autoimmune disease, where the immune system’s perception of threat invades its recognition of self.

The ECS has been extensively studied and shown to be a major player in the development of stress-related disorders as well as in their treatment and resolution. The ECS controls excessive activity in the emotional and memory centers of the brain, and the therapeutic use of cannabinoids have been shown to help extinction of fear memories, prevent reinforcement of fear memories after trauma reminders, reduce the impact of stress on cortisol levels and immune function, and relieve symptoms of stress-related disorders such as anxiety and insomnia (17). Interestingly, there’s evidence that people with ECS dysfunction, such as a mutation in the gene that codes for the CB1 receptor (18) or lower levels of circulating endocannabinoids (19) have an increased likelihood of developing PTSD; there’s also evidence that the ECS is dysregulated in autoimmune conditions such as MS (20).

In medicine we often speak about “stress reduction” with an assumption that all psychological stress is damaging, but this is certainly not the case. It’s well-known that certain types of physical stress, like exercise, are healthy, but what defines healthy psychological stress, and what does this have to do with cannabis?

 is a form of stress that has a beneficial effect on our health, motivation, performance, and emotional well-being. This type of stress feels challenging but exciting and within our coping ability. Eustress usually occurs when we embrace both the challenging and supportive aspects of an event or situation.

 is another form of stress that leads to anxiety, depression, impaired performance, and feeling overwhelmed. It typically occurs when one perceives the challenging aspects of an event or situation without simultaneously perceiving the supportive aspects. Eustress and distress are associated with vastly different responses in brain function and physiology.

I find it fascinating that the stressful situation itself doesn’t determine the type of stress, but our perception of the situation does. Nearly every situation has both challenging and supportive aspects, but we so often chose to fixate on the challenge while ignoring the support. Why? We all have the power to transform distress into eustress and spare ourselves the emotional and physiological consequences, so why do we so seldomly exercise this choice?

Because our environment is full of far more stimuli than our capacity for perceiving, our brains develop perceptual filters that help us focus on certain things and ignore others. Over time, and especially if left unattended, our filters often orient toward threatening aspects of our environment and away from supportive ones. This is especially true for those of us that have experienced trauma, which is generally everyone. Rigid perceptual filters limit our capacity to make the choice to perceive both sides of the situation and experience eustress instead of distress.

Why so much discussion about stress in an article on autoimmune disease? Among my patients with these conditions, many find that beyond the symptom-relief that cannabis provides, which they celebrated early in their use of the medicine, the perceptual flexibility learned from their long-term cannabis use is its most valuable gift. My patients find that cannabis helps them experience acceptance of stressful situations and their disease itself, feel as if they are a part of something greater than themselves like nature or God, and at the same time feel more like themselves.

Interestingly, qualitative research on cannabis-using patients has also found this common theme. Authors proposed the term “restored self” to describe this benefit of cannabis, defined as “the experience of regaining one’s sense of self, sense of normality, and sense of control over one’s life,” (21). Remarkably, this benefit was experienced independently of whether or not the individual experienced symptom relief with cannabis.

My patients with autoimmune disease often describe, in other words, an enhanced capacity to experience eustress instead of distress, which decreases the frequency of symptom flares and improves their overall quality of life. While the increased perceptual flexibility is often first experienced during the acute psychoactive effects of THC, after some time repeatedly using cannabis, they are able to maintain this flexibility with or without cannabis on board, suggesting a long-lasting transformation in stress resilience. In this way, perhaps cannabis strikes closer to the cause of the autoimmune disease, healing a dysfunctional perception of support and challenge, a dysfunctional sense of self and non-self.

Long-lasting perceptual flexibility isn’t the only benefit of cannabis that impacts autoimmune disease deeper than symptom reduction. For most patients, temporary symptom relief isn’t enough; a treatment that prevents disease progression, prevents tissue damage, and perhaps promotes remission is crucial. In conventional medical care for several autoimmune diseases, a category of otherwise unrelated drugs, called disease-modifying antirheumatic drugs (DMARDs) is defined by the capacity to slow down disease progression. Many of the DMARDs work by suppressing the production or activity of the immune systems’ inflammatory signals such as tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), interleukin-6, and by inducing apoptosis (death and recycling) of B cells and T cells.

Not surprisingly, given its broad ability to replace multiple classes of pharmaceuticals, cannabis is able to perform many of the same functions as the DMARDs. The ECS is already working via some of these same mechanisms to prevent and regulate autoimmune diseases, and many of the effects of cannabis are simply enhancing this inherent function.

Specifically, THC has been shown to induce apoptosis reduce proliferation of B cells and T cells, while increasing the number of T regulatory cells, which are beneficial in autoimmune disease; CBD also triggers apoptosis of certain T cell subtypes that contribute to autoimmune inflammation. THC and CBD both inhibit release of the pro-inflammatory Th1 cytokines such as IL-1 and TNF-α; tetrahydrocannabinolic acid (THCA) also has potent anti-TNF-α activity. THC and CBD have been shown to increase production of Th2 cytokines that counteract the effects of Th1 cytokines. Cannabinoids have also been shown to decrease the activity of 

 which are enzymes implicated in cartilage destruction in autoimmune conditions like rheumatoid arthritis (22).

Remarkably, the immune systems of people who regularly use cannabis may be more responsive to its anti-inflammatory effects than new users, demonstrated in a study in which phytocannabinoids inhibited the migration of monocytes taken from the blood of regular users, but did not affect migration of the monocytes taken from non-users. The regular users’ monocytes had four times higher expression of CB1 mRNA, indicating the cells had more CB1 receptors and therefore a stronger response to THC (23).

How to Use Cannabis in the Treatment of Autoimmune Conditions

“Treat the individual, not the diagnosis” is my most common answer when people ask me how to use cannabis to treat a specific condition or category of conditions such as autoimmune disease. With its diverse range of chemical compositions, delivery methods, safe and effective dosages, and significant interindividual variability, cannabis requires us to take a more individualized approach to medicine—a benefit to patients. Nevertheless, there are certain strategies I suggest for most patients with autoimmune disease:

Use cannabis to promote healthy, restorative sleep.

Disturbed sleep can promote immune system dysfunction, increase sensitivity to pain, decrease resilience to stress, and much more.

I recommend low doses of inhaled cannabis (sedating varieties only) to help fall asleep and orally delivered cannabis to help stay asleep and to deepen sleep.

Though some people find success treating sleep disturbances with CBD, I find the best results are usually achieved with THC-dominant cannabis.

Many patients wait until after work to use cannabis—this is not ideal in autoimmune disease because some of the anti-inflammatory effects of cannabis are short-lived.

Daytime administration of CBD and cannabidiolic acid (CBDA) combined with approximately one fourth of one’s optimal nighttime dose of THC is often well tolerated and effective at reducing symptoms.

THCA and CBDA are highly absorbable when taken orally and have profound anti-inflammatory effects. While not usually as rapidly effective as THC in reducing symptoms, I’ve found that most patients who consistently take acidic cannabinoids 2-3 times daily for 2 weeks reports significant improvements in inflammatory symptoms.

If products containing THCA and CBDA are available, I recommend starting with 10 mg of each per dose and gradually increasing if needed. Some people do well with higher doses of CBDA up to 100 mg per dose.

If you don’t have access to such products, simply make cannabis tea. On average, an 8-ounce cup of cannabis tea made from a ¼gram of aTHC-dominant variety contains approximately 10 mg of THCA and 2 mg of THC, a nice dose for many people. If you add creamer or any oil to your tea, be prepared for a higher dose of THC.

THC tolerance occurs via downregulation of the CB1 receptors; CB2 receptors likely also downregulated when this occurs. This means that if you are less able to feel the psychoactive and symptom-relieving effects of cannabis, you are probably also less able to benefit from some of the anti-inflammatory and immune-regulating effects.

Most people who lose the benefits of cannabis over time assume that increasing the dose is going to improve efficacy, which it may do temporarily, followed by more tolerance-building. The more effective but counterintuitive strategy, however, is to reduce the dose, allowing upregulation of CB receptors and restoration of responsiveness to cannabis.

For those who suspect they’ve developed tolerance to cannabis, Healer.com provides a complimentary protocol, complete with videos and worksheets, to guide people through a cannabis sensitization process and discover an optimal dose of THC.

Unlike THC, it’s much harder to build tolerance to the benefits of CBD and CBDA. Liberal dosages of both are usually well-tolerated and non-psychoactive, a good choice for daytime treatment.

While many patients new to cannabis will at first wish to avoid its psychoactive effects, eventually I find the opportunity to introduce them to what might be the most therapeutic aspect of this plant.

People who regularly use oral THC before bed can periodically take their regular dose a few hours early to explore the psychoactive effects of THC while awake. I often encourage them to turn off the screens, put on some music, pick up a journal, or other specific suggestions to increase the likelihood of a therapeutic experience.

For those open to inhaled cannabis, this is usually the best way to appreciate its perceptual gifts because of the rapid onset and easily observable transition of one’s perspective of life’s stressors. It can support introspection and reflecting on one’s day, enhance healing practices like yoga and chi kung, deepen intimacy, and much more.

In summary, autoimmune diseases are common and originate in the immune system’s (and often one’s conscious) dysfunctional perception of self and non-self. Cannabis can provide excellent symptom relief for pain, sleep disturbance, itching, spasticity, anxiety, gastrointestinal, and many other symptoms. Some conditions, like MS, have significant clinical trial data supporting the effectiveness of cannabis, while most autoimmune diseases have little data beyond patient surveys, which usually indicate excellent results. Stress is a major factor in the development and progression of autoimmune diseases; cannabis can improve resilience to stress via its acute anti-anxiety effects and via long-lasting improvements in perceptual flexibility and ability to experience eustress instead of distress. Finally, cannabis also treats many underlying factors of autoimmune disease, conveying many of the benefits of DMARDs without the side effects and likely reducing the progression and damage caused by these conditions.

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Arthritis & Rheumatism: Official Journal of the American College of Rheumatology 

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 

, one of the first physicians in Maine to incorporate the legal use of cannabis as a medicine in 2009, is the founder of Integr8 Health, a medical practice that follows more than 8000 patients using medical cannabis. Today he is globally recognized by his peers as a pioneer of clinical applications, formulations, and usage protocols. He is the author of the first foundational text on the clinical use of cannabis and cannabinoid therapies, titled 

Handbook of Cannabis for Clinicians: Principles and Practice

Here, Dr. Dustin Sulak shares how stress is a major factor in the development and progression of autoimmune diseases and how cannabis can be a great tool in alleviating symptoms.

Carla Basante began using cannabis about 15 years ago to manage chronic pain from a severe back injury and symptoms of multiple sclerosis (MS). A breast cancer survivor, Carla has had two back surgeries to treat the damage caused by a bad car accident when she was in her early 40s, as well as a nerve ablation, and other procedures.

After doctors had trouble explaining the various symptoms she was experiencing after that accident, an MRI revealed she was also suffering from MS. The trauma of the back injury had “activated” her lurking MS, leading to seizures and other debilitating problems. What followed was a medicine cabinet full of powerful pharmaceutical drugs.

“Oxy, Percocet, Valium – they’d prescribe anything, even steroids,” Carla remembers. The unpleasant side effects of the medications she was initially prescribed for her conditions led her to investigate alternatives.

“My son was a factor. I wanted to be a mother, but I didn’t recognize myself,” Carla says.

She found that cannabis provided relief without the many side effects of other medications. Once she found a cannabis regimen that worked, she was able to go take herself off of 10 drugs.

“It’s horrible to live with chronic illness and chronic pain, but it’s been years since I’ve had to take steroids, and I haven’t had MS episodes,” Carla says. “If I wasn’t medicating with cannabis, I couldn’t function.”

Her research on medical cannabis also led her to Americans for Safe Access (ASA). She has attended ASA’s annual unity conference in Washington, D.C. three times, first in 2017, and has lobbied on Capitol Hill.

“That ASA conference changed my life,” Carla says. “I met patients from all walks of life – lawyers, doctors, parents of children with Dravet Syndrome.”

Carla’s direct advocacy work began when she had to go in for another back surgery and was told she couldn’t use cannabis at the hospital. After her procedure, she was sent to a rehabilitation center that weekend, the staff asked her if she was using any medications. When she told them, yes, she used cannabis, the staff said they were sorry, but this was a “no flame” facility.

“No problem,” Carla said. “I’ve got a vape pen, so no flame.”

Stumped by that, the nurse set up a medication schedule with her for her cannabis use. When the administrative folks returned to work on Monday, they told Carla she’d have to stop.

“I told them, no, we’ve already got a schedule, and it’s not causing anyone any problems,” Carla recalls. They said she would have to switch to dronabinol, the Food and Drug Administration’s (FDA)-approved synthetic tetrahydrocannabinol (THC) medicine. Instead, Carla opted for cannabis oils and medicated baked goods.

In the future, Carla would like to see cannabis be more available to those in need, and for medical facilities to provide cannabis lounges for patients so that they can get the treatment they prefer to use.

“The number of pills being doled out is frightening, particularly for our elderly population. It’s a free for all,” Carla says. “If they were able to use cannabis in different forms, it would save them from the dangerous side effects.”

Carla was back at that rehab center a year ago because her mother was receiving care there and was surprised to have the staff remember her.

“I was wearing a mask, but aides were pointing. ‘You were here before,’” Carla says. “They remembered me going outside in my wheelchair to use the vape pen.”

Carla’s self-advocacy had made an impression.

“My thing is cannabis use for facilities, hospitals, prisons, nursing, rehab, even schools – all the places that receive federal funds and say you can’t use cannabis as medicine,” Carla says. “I have a friend with a son in high school in New Jersey who is finally able to administer his cannabis in school.”

Because of her son, Carla has had to deal with the anti-cannabis messages common to schools. He was 7 years old when she started using cannabis, and she worked to educate him about “mom’s medicine”, but things changed when he got to middle school and was exposed to strident anti-cannabis messages. Carla had been showing him ASA materials and her collection of books about the medical uses of cannabis, but the conflicting messages led to arguments. He wanted her to stop.

“I’m more engaged, more active – don’t you see the difference?” Carla remembers asking him. “It’s not taking away all the pain, not curing MS, but now I’m functional. Isn’t that what we want? I wouldn’t be able to hold a job without it.”

When her son told her about a poster in his guidance counselor’s office that said cannabis use leads to cocaine and other hard drugs, she went to the school, much to her son’s embarrassment.

“Why would you have this up?” Carla asked the guidance counselor. “You’re an educator. Why would you not educate yourself?”

She remembers her son’s complaints about how she was bringing attention to her cannabis use.

“I know,” she told him. “You know how much this has helped me.”

It was a hard three years, but by the time her son got to high school, the switch had flipped. He saw the stigma was wrong. When he got to college, he discovered his university has a cannabis curriculum and took a couple of courses.

“I’ll always remember the smile on his face when he said, ‘Look what they offer!’” Carla says. “That’s the best thing ever.”

From that experience, Carla has learned that we must do cannabis education one on one, whether that is with children or medical professionals. She makes use of expert resources, but she also knows her own story makes a powerful case.

“I’m the healthiest unhealthy person, thanks to cannabis use,” Carla says.

This profile was previously published by Americans for Safe Access in their March 2022 ASA Activist Newsletter. To see the original newsletter, please visit 

https://www.safeaccessnow.org/asa_activist_newsletter_march_2022

 produces Americans for Safe Access’s (ASA’s) monthly Activist Newsletter and has been part of ASA’s communications team since 2002. He is the co-author of 

The Medicalization of Marijuana: Legitimacy, Stigma, and the Patient Experience, 

an award-winning book of medical sociology, and has published hundreds of articles on cannabis and other topics. He has taught at a number of colleges and universities, including UC Berkeley, and is currently working on a book about cannabis use and mental health.

Carla Basante discusses how she began using cannabis about 15 years ago to manage chronic pain from a severe back injury and symptoms of multiple sclerosis (MS).

Once upon a time, a newly retired career board certified anesthesiologist, Dr. Janice Knox, began getting into more natural medicines, using the natural curiosity that was always part of her 35 years of work as a doctor. She had married a doctor in 1977, Dr. David Knox, and their two daughters, Jessica and Rachel, would follow in their parents’ footsteps, leading them all to work with cannabis as medicine for better patient wellness.

Dr. Knox said that she was introduced into the cannabis space because she was invited to work at a clinic that wrote medical cannabis cards—cards that are issued by the government for those who qualify or have a medical condition. “At first I hesitated to do that because I absolutely knew nothing about cannabis,” she explained.

She had attended the University of California-Berkeley as an undergraduate in the 1970s, where the student culture included lysergic acid diethylamide (LSD) and cannabis as a key part of their social scene. “I absolutely knew nothing about cannabis, even after spending all those years at Berkeley,” she said. “So, I hesitated initially because of that.”

But she decided to go ahead and see who showed up to get their medical cannabis card—and it became a life-changing moment for her. “I was shocked by who I saw come through the door of the clinic, because they looked like everyday people. They were retired people, doctors, lawyers, grandmothers, grandfathers, parents bringing their babies, and parents bringing their teenagers. So, I’m going ‘Oh my god, who are these people?’”

It quickly became apparent to her that these people were spending their last bit of money for cannabis because conventional medicine had failed them. “I was so intimidated, or shocked, because here I was an anesthesiologist who knew physiology and pharmacology. But I couldn’t tell them a thing about cannabis.”

Invigorated by what she saw, and with her curiosity piqued, she then proceeded to dig into finding out what the cannabis plant offered. “When I found that information out, I was shocked at the medicinal benefits of cannabis. And then I dug into why it was banned,” she said. “When I read the congressional records, I was shocked again. And then I dug a little deeper because I liked looking under the hood, as it were. When I found the physiology that supported the use of cannabis, then I became a real advocate” (1).

Then Dr. Knox started putting together the pieces of the puzzle about patient treatment from what she had witnessed as an anesthesiologist over her long career and began connecting the dots about the benefits of medical cannabis that would quickly build up her interest.

“Before I left my anesthesia practice, one of the final sights that sticks in my mind to this day is what the recovery room looked like,” she said. “There were patients who had been put on just tons of pain medications and were screaming for more. All I could think of is that what we’ve done is created drug-seeking patients. They came to surgery on these massive amounts of drugs and as an anesthesiologist, I had to juggle those medications, and keep them safe through all of this. I started thinking ‘Oh my goodness, what have we done here’?”

She said that she thought all medical professionals, including clinicians like her, and their patients, were trained in a certain way about pharmaceuticals and therapy for patients. “We all believe anything that comes from the pharmaceutical industry is okay to take,” she said (2). “But it can have a list of 50 side effects. I tell patients the further we move away from what’s natural, the more complications we’re going to see.”

Dr. Knox recalled a patient who called her and told her that her son was on a certain pharmaceutical drug. “We don’t like giving kids Paxil because it puts them in a dark place,” explained Dr. Knox. “But once again, we have been so brainwashed about what’s acceptable, that people are terrified of cannabis. We’re seeing great results and long-term results with cannabis. But you pose using cannabis to a patient, and they say ‘Oh, no, no, no, I can’t take that.’”

She believes that it’s about educating the public and educating clinicians. “We just have to think differently. And we’re just not there.”

Dr. Knox said that she has always been a disrupter, something she attributes to her educational fine-tuning at Berkeley where students are taught to be disruptive. They are taught to ask the extra question. “I’ve always looked at things like why a certain treatment or drug works. And why this treatment or drug isn’t working. So, I was already asking the extra question,” she said. “I knew that, with the conventional medical process as we know it, we’re not answering questions. I knew we needed to look elsewhere.”

Along her pathway to better understanding the benefits of cannabis as medicine, both her husband, Dr. David Knox (an emergency room doctor for more 40 years) and their two daughters, Dr. Jessica Knox and Dr. Rachel Knox (3), became convinced she was on to something important that impacted them all. “I told my husband that I’m a trailblazer. I always dance and walk to a different tune. And when he saw what I was doing, and the difference I was making with cannabis, he came on board. He was intrigued,” she said.

She thought that her daughters were thinking OK, there goes my mom doing something crazy again. “As far as using the cannabinoids, they began to understand it, and looked at what I was doing. Then they joined me,” she added.

Being people of color, she said, means that she and her family look at things a little differently anyway. “Why does cannabis work? And what makes it work? And then, we began learning about the endocannabinoid system.”

She said that, in her deep dive to figure out more about cannabis—trying to understand why people would choose this plant and why it worked—she found out about the endocannabinoid system. “It is the backbone to which every other physiological system is based,” Dr. Knox said. “It is the system that keeps harmony and balance between all our physiological systems. We’re looking at receptors triggering downstream effects that cause a result. I was shocked. How did I learn physiology in medical school and didn’t learn about this system that controls all of that physiology I learned about?”

When looking at the bigger picture of the endocannabinoid system like she did, she said, she begin to understand that this really isn’t about cannabis. “It’s about our understanding that physiology, and how do we explain the function and dysfunction of that physiology?” she said. “And that is something that should always come first.”

That a-ha moment was the impetus for the development of Dr. Knox as an 

, a term she coined—meaning a person who studies the function and dysfunction of the endocannabinoid system, and how to clinically apply what has been learned about cannabis and other botanicals as it pertains to the endocannabinoid system.

The Autoimmune System and Endocannabinoids

In discussing the autoimmune system, Dr. Knox has a very specific cannabis-angle viewpoint. “If we understand the things that throw the endocannabinoid system off, then you can start to apply the information that we need, right?” she said.

She explained that everything, regardless of the disease process, or the system that is being discussed, starts at the cellular and sub-cellular level. “The things that throw the endocannabinoid system off are genetics, the aging process, nutrition, pharmaceutical drugs, environmental stressors—these are all of the things that drove the endocannabinoid system off so it can’t do its job.”

The root cause of throwing off the endocannabinoid system can also be traced to the inflammation that we start to gather in our body “probably from day one,” she said, because of the world we live in. “A root cause of most disease processes, if not all, is inflammation. But that inflammation leads to other disease processes. How that disease is manifested depends on your genetics and the environment you grew up in.”

Some people may show cancer, others will show diabetes or an autoimmune disease. “What you try to do regardless of the disease process is to understand the root cause of disease processes,” she said.

According to a July 2021 study done by Italian researchers (4), the endocannabinoid system (particularly CB2 receptor activation) is a possible target for the treatment of inflammatory and the autoimmune diseases related to immune cell activation. The study concludes that: “In vitro and animal studies of multiple sclerosis have provided convincing evidence of the immunomodulatory properties of cannabis, although there is still a lack of clinical evidence from randomized and controlled clinical trials.”

In other words, what those researchers found out was just a start—there’s much more work to do.

If she is talking to somebody with an autoimmune disease, Dr. Knox said that she is going to look at what system is most affected. “For example: Is it the joint system? And then work from there to see which receptors are not working or which are overworking and see how to put a therapy plan or a treatment plan together.”

If she sees someone with breast cancer, she is going to treat that person differently than someone with an autoimmune disease (5), or with brain cancer, because different receptors are involved.

“Patients come in with this disease process, including autoimmune disease, whether it’s rheumatoid arthritis or psoriasis, or all kinds of things, such as inflammatory bowel disease,” Dr. Knox said. “We try to put the patient in the forefront of their therapy. We can only do so much as they will allow us to do or tell us about, and sometimes they don’t even understand why they’re getting sick.”

“So, if I’m treating someone with autoimmune disease, I want to know everything about them. I want to know what environment they live in. Is it a food issue or a water issue or an air issue? Is it a soil thing that has triggered their autoimmune disease? Is it stressors in your apartment? Is it financial stress, emotional stress, and what’s happening with their family or personal economics? That includes the medications they’re on, and how they relate to their doctors. All those things become so important, so that we can start to turn their health picture around.”

Even with a better understanding of the autoimmune system, today’s informed medical doctor sometimes still has to watch and wait—and hope—for their patient to improve. “I tell patients that none of us have that crystal ball to say how long you’re going to live, and when you’re going to die,” she said. “But statistics tell us that cannabis has a higher success rate with treating autoimmune issues than those of pharmaceutical drugs or the anti-cancer agents, and that those two working together—cannabis and pharmaceuticals—have a better outcome than any one individually.”

The key to helping patients is to tell them that it’s not cannabis alone. “We can’t just tell you to go out and buy these cannabinoids or these terpenes and it’s going to be okay,” Dr. Knox said. “A patient has to buy into every last bit of what the therapy is, including believing that they can heal. We’re so focused on illness and sickness and treating that sickness, and we’re not really focused on moving patients back to wellness. What cannabis has taught us is we need to look in other places and move patients back to wellness.”

The American Cannabinoid Clinics (ACC) (6), which were co-founded by Dr. Knox, her daughter Dr. Rachel Knox, and her husband Dr. David Knox, along with the organization’s CEO, her other daughter, Dr. Jessica Knox, was a clinic where these cannabinoid and endocannabinoid system specialists managed patients’ use of cannabinoid therapies, natural foods and supplements, and cannabimimetic practices (such as detoxification, oxygenation, yoga, meditation, and exercise) according to the underlying function or dysfunction of the endocannabinoid system.

The ACC was closed and rebranded as Pivital Health (7) last year, Dr. Knox said, which is an interactive education program in cannabis, cannabinoid medicine, and endocannabinology developed by her and her daughters—the so-called Knox Docs. “Patients come to us to get a deeper consult, such as an hour-long consult on occasion, instead of the 15-minute visit with a signature on a piece of paper so you can get your card, like we did at the ACC,” she said. “We will delve into what their health and their lifestyle has been. We delve into their disease processes.”

The patients can’t be given cannabis, but the clinicians at Pivital Edu can suggest certain terpene profiles or cannabinoid profiles.

There needs to be a lot more education, Dr. Knox said, but medical practitioners need providers to understand not just tetrahydrocannabinol (THC) and cannabidiol (CBD), but why they are recommending it. “What do you hope to accomplish? And how do you use it? I want them to feel comfortable,” she said.

Dr. Janice Knox discusses how she took a deep dive into medical cannabis, the formation of the famous Knox family of endocannabinologists.