Lupus is hard to treat, could regulation of the endocannabinoid system through cannabis medicine make all the difference?
Systemic lupus erythematosus, or lupus for short, is an autoimmune disease affecting multiple organ systems. The etiology of the disease is still not fully understood but it is accepted that the immunological defects leading to lupus development can be divided into two phases. In the first phase, antibodies against one’s own molecules start developing, called the anti-nuclear and anti-glomerular antibodies. In the second phase the derangement in the immunological balance leads to destruction of various organs, including the kidneys resulting in nephritis.
All these events culminate in organ damage. Due to the lack of understanding of underlying factors in lupus, therapeutic strategies are scarce, and usually rely on the use of immunosuppressants and corticosteroids, which carry with them a plethora of associated side effects. Needless to say, improvements on the therapeutic front are crucially needed.
This is why recently a group of researchers looked into the potential involvement of the cannabinoid system in lupus. There are two endogenous cannabinoids (anandamide and 2-AG) that have shown to play important roles in both physiological and pathological processes, including autoimmune diseases.
It is generally accepted that these molecules are synthesized on demand, and in regulated fashion. Derangements in the endocannabinoid system have been observed in 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 an elevated level of the enzyme responsible for its production.
Interestingly, they also found that among lupus patients higher 2-AG levels were associated with lower stage of the disease. In other words, patients whose disease severity was lower showed higher 2-AG levels, suggesting a protective role of this endocannabinoid. It is still unclear as to the causality of higher 2-AG in lupus patients, an whether the endocannabinoids system initiates its production in order to alleviate the destructive forces of the overactive immune system. It is also interesting that anandamide but not 2-AG is elevated in patients with other autoimmune diseases (i.e. multiple sclerosis).
This may be suggestive that 2-AG may potentially be used as a marker for lupus in the blood plasma when distinguishing 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 finding that the endocannabinoid system is dysregulated in lupus lies in the potential of using exogenous cannabinoids, such as THC and CBD to correct this imbalance serving a therapeutic purpose . In fact, a phase 2 clinical trial commenced in December of 2017 evaluating efficacy, safety and tolerability of CB2 agonist which 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 will be produced.