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16 doctor focus cannabis patient care | vol. 3 no. 2 cannapatientcare.com 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 support- ive ones. This is especially true for those of us that have experi- enced trauma, which is generally everyone. Rigid perceptual fil- ters 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 auto- immune disease? Among my patients with these conditions, many find that beyond the symptom-relief that cannabis pro- vides, which they celebrated early in their use of the medi- cine, 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 sit- uations 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 nor- mality, and sense of control over one's life," (21). Remarkably, this benefit was experienced independently of whether or not the in- dividual experienced symptom relief with cannabis. My patients with autoimmune disease often describe, in other words, an enhanced capacity to experience eustress in- stead of distress, which decreases the frequency of symptom flares and improves their overall quality of life. While the in- creased perceptual flexibility is often first experienced dur- ing 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 autoim- mune disease, healing a dysfunctional perception of support and challenge, a dysfunctional sense of self and non-self. Cannabis, the ECS, and Immunomodulation Long-lasting perceptual flexibility isn't the only benefit of cannabis that impacts autoimmune disease deeper than symp- tom 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 multi- ple classes of pharmaceuticals, cannabis is able to perform many of the same functions as the DMARDs. The ECS is al- ready 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 re- duce proliferation of B cells and T cells, while increasing the number of T regulatory cells, which are beneficial in autoim- mune 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 cy- tokines 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 metalloproteinas- es, 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 ef- fects than new users, demonstrated in a study in which phytocan- nabinoids inhibited the migration of monocytes taken from the blood of regular users, but did not affect migration of the mono- cytes 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 autoim- mune 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 dys- function, increase sensitivity to pain, decrease resil- ience 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