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15 doctor focus cannapatientcare.com july/august 2022 | cannabis patient care 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% high- er in those with the stress-related disorder. Some conditions, such as autoimmune thyroid disease, had a stronger associa- tion 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, ac- tivation of the sympathetic (fight or flight) nervous system and increased levels of the stress hormone cortisol can im- pair immune function, potentially increasing susceptibility to and preventing recovery from infections that could trigger au- toimmune disease. In patients with PTSD and other types of chronic stress, particularly related to early life trauma, "ad- renal 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 indirect- ly influences the risk for autoimmune disease via lifestyle fac- tors such as sleep disruption, alcohol or substance abuse, and increased smoking. Metaphorically, severe stress is usually related to the percep- tion of uncontrollable threatening elements in one's external en- vironment, 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 reinforce- ment 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 anxie- ty and insomnia (17). Interestingly, there's evidence that peo- ple 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 devel- oping 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 as- sumption that all psychological stress is damaging, but this is cer- tainly not the case. It's well-known that certain types of physical stress, like exercise, are healthy, but what defines healthy psycho- logical stress, and what does this have to do with cannabis? Eustress 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 cop- ing ability. Eustress usually occurs when we embrace both the challenging and supportive aspects of an event or situation. Distress is another form of stress that leads to anxiety, de- pression, 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 situ- ation does. Nearly every situation has both challenging and supportive aspects, but we so often chose to fixate on the Figure 2: The two types of stress: eustress and distress Embrace both challenging and supportive aspects of an event or situation Perceive challenging aspects of an event or situation without perceiving the supportive aspects Perception Eustress Distress • Beneficial effect on health, motivation, performance, & emotional well-being. • Feels challenging but exciting and within our coping ability. • Anxiety • Depression • Impaired performance • Feeling overwhelmed