Targeting cannabinoids to the gut-associated lymphoid tissue (GALT) for improved treatment of autoimmune diseases

Autoimmune diseases are conditions that are triggered by the immune system initiating an attack on the body’s own molecules. The causes of such attacks in most cases are unknown, but a number of studies suggest that they are associated with factors such as genetics, infections and environment. There are currently more than eighty different autoimmune diseases. Examples include debilitating conditions such as multiple sclerosis, systemic lupus erythematosus, arthritis and Grave’s disease.
There has been a long debate in the literature regarding the potential benefit of immunomodulatory effects of cannabinoids in the treatment of autoimmune diseases. These effects are based on the inhibition of immune cells (macrophages, T and B lymphocytes, natural killer cells) by cannabinoids via the cannabinoid receptor 2. Cannabinoids are highly lipophilic compounds. There are multiple reports that co-administration of lipophilic compounds with long-chain triglycerides (LCT) facilitates the intestinal lymphatic transport of these molecules. Lymphatic transport leads to extremely high local concentrations of lipophilic compounds in the lymph fluid and nodes. The delayed absorption of drugs when they are transported via the lymphatic system suggests that there could be several hours retention of cannabinoids in mesenteric lymph nodes following a single oral administration.
The rationale of this project is that oral administration of lipophilic cannabinoids with LCT facilitates the intestinal lymphatic transport and, thereby, creates high local concentrations of these molecules in the mesenteric lymph nodes and significant immunomodulation effect. We hypothesize that administration of lipophilic cannabinoids in conditions that facilitate lymphatic transport would result in a more efficient treatment of autoimmune diseases.
Over the last 3 years substantial in vitro and in vivo preliminary data have been generated in our laboratory. These data demonstrate the immunomodulatory activity of cannabinoids, as well as very significant intestinal lymphatic targeting with very high concentrations obtained in gut-associated lymphoid tissues (GALT).
Therefore, the aims of this PhD project will be focused on establishment of animal models of a number of autoimmune diseases, and demonstration of the efficacy of the GALT-targeting of cannabinoids in these animal models. The second half of the PhD will be focused on small-scale clinical studies that involve patients that suffer from the autoimmune disease that have been modelled in the in vivo studies.