Could cannabis help regulate the endocannabinoid system of lupus patients?
Systemic lupus erythematosus (or lupus for short) is an autoimmune disease affecting multiple organ systems. We don’t fully understand the etiology of the disease. Still, we accept that the immunological defects of lupus development can divide into two phases. In the first phase, antibodies against one’s own molecules start developing, called anti-nuclear and anti-glomerular antibodies. In the second phase, the derangement in the immunological balance destroys various organs (including the kidneys) creating nephritis.
All these events cause organ damage. Unfortunately, because of our lack of understanding the underlying factors in lupus, therapeutic strategies are scarce. They usually rely on the use of immunosuppressants and corticosteroids, which carry a plethora of associated side effects. Needless to say, we crucially need improvements on the therapeutic front.
The First Study of Lupus and the Endocannabinoid System:
Recent research studies the cannabinoid system’s potential to fight lupus. First, there are two endogenous cannabinoids (anandamide and 2-AG) playing important roles in physiological and pathological processes, including autoimmune diseases.
Doctors generally accept the theory that these molecules synthesize in regulated fashion and on demand. These doctors observed derangements in the endocannabinoid system, proving it affects autoimmune diseases including multiple sclerosis, rheumatoid arthritis, psoriasis, and systemic sclerosis. This is the first study to investigate the status of the endocannabinoid system in lupus. They found that lupus patients had elevated 2-AG levels in the blood plasma, due to the elevation of the level of the enzyme responsible for its production.
Interestingly, they also found lupus patients have higher 2-AG levels. These higher levels associate with the lower stages of the disease. In other words, patients whose disease severity is lower show higher 2-AG levels, suggesting a this endocannabinoid plays a protective role. The causality of higher 2-AG in lupus patients is still unclear. One theory is that the endocannabinoid system initiates 2-AG’s production to alleviate the destructive force of the overactive immune system. It is also interesting that anandamide but not 2-AG elevates in patients with other autoimmune diseases (i.e. multiple sclerosis).
Other Autoimmune Diseases:
The study suggests that 2-AG may potentially see use as a marker for lupus in the blood plasma to distinguish among various autoimmune conditions. In other autoimmune diseases THC and CBD have shown some promising aspects in curtailing the overactive immune system in animal models. THC has been shown to inhibit neurodegeneration due to reduced inflammation in multiple sclerosis. In rheumatoid arthritis, CBD and cannabis have been shown to have anti-inflammatory effects and to reduce joint damage. In ulcerative colitis, it has been suggested that exogenous cannabinoids can be used therapeutically because of reduced AEA synthesis and the existence of both CB1 and CB2 receptors on intestinal lining.
The importance of this study is the discovery that lupus disregulates the endocannabinoid system. It means doctors have the potential to use exogenous cannabinoids. THC and CBD could correct this imbalance and to serve a therapeutic purpose. In fact, a phase 2 clinical trial commenced in December of 2017 evaluating efficacy, safety and tolerability of a CB2 agonist they named JBT-101 in resolving immune responses without immunosuppression. This is a double-blind, placebo controlled, randomized multicenter trial involving one hundred lupus patients and as such is promising in terms of scientific rigor and the quality of data that it will produce.
