Large spectrum of therapeutic properties of medical cannabis has been an object of discussion within many different contexts such as clinical applications, scientific research or pharmaceutical reality, often being either very promising or filled with large portion of skepticism. Besides already well-established therapeutical applications such as chronic pain, cancer, anorexia and epilepsy, list of medical cannabis treatments is long, targeting also psychological disorders such as Tourette’s syndrome, depression or schizophrenia. Due to the lack of sufficient clinical studies we still don’t have full clarity on subject of appliances and classification of all use and effects, however significant amount of recent scientific research done on endocannabinoid system (eCB) strongly suggests there is another therapeutic target in our body for phytocannabinoid treatments.
Numerous indicators show how strongly our brain is connected to our gut, creating a unique physiological system of control and if something goes wrong on the line, we often face heavy medical consequences. Problems in our gastrointestinal system have also proven to be influencing strongly our psychological state and might lead to mental disorders including depression etc.
Endocannabinoid receptors are located everywhere in our body, regulating different systems and connecting many processes, often playing a lead role and influencing our homeostasis. Increased recent scientific research on eCB system role in our gastrointestinal tract points out high importance of eCBs in regulating the health of our gut, which is a large and long microbiome that can contain over 400 different bacterial strains, making interactions and their regulation mechanism very complex.
One of the most known eCB gut players are the AEA and 2-AG (anandamide and 2-Arachidonoylglycerol) and two receptors, CB1 and CB2. Many different scientific discoveries unveiled a tight link between eCB, gut inflammation and gastrointestinal cancer. Different findings show increasing and decreasing levels of either AEA or CB1 receptor expression in gut, which change significantly in the presence of gut inflammation, antibiotics treatment, cancer or elevated stress. Inhibition of FAAH (enzyme responsible for degradation of AEA) led to reduced inflammation and promoted gut healing, suggesting direct correlation between AEA and gut homeostasis. Furthermore, AEA has also been observed to have increased levels during gastrointestinal cancer and chronic gut inflammation. Endocannabinoids have not only healing but also protective roles, 2-AG being a shield against pathogens such as Enterobacteriaceae, Citrobacter or Salmonella typhimurium.
While endocannabinoid impact on our gastrointestinal system remains still not fully discovered, certain eCB mechanisms were already used to look for possible treatments. Application of medical cannabis has proven the potential to cure inflammatory bowel disease and is being widely used as a valid therapy, sending a strong signal that it can be used to help with various other gastrointestinal issues. Majority of medical cannabis patients treated for inflammatory bowel disease have shown improvement in the discomfort and pain. While AEA and 2-AG increase the permeability of the gut during inflammation, THC and CBD help in its restoration. CBD has also been reported to reduce gut inflammation by binding to GPR55 receptors.
Treatments with antibiotics cause large disturbances in microbial stasis of the gut, often leading to inflammation as well, moreover, it has been recorded that AEA levels drop significantly during the treatment. The administration of THC to obese mice has already proven to influence the intestinal fauna, leading to improvement and decrease in obesity. eCB system plays also crucial role in gut permeability and absorption of fatty acids, regulating the body weight. Different levels of AEA and 2-AG have been noted in individuals following different diets, where palatable and rich western diet caused increased AEA and 2-AG levels while lighter Mediterranean diet caused 2-AG levels to drop. In general, increased AEA levels are highly correlated with obesity in humans, suggesting many possible molecular pathways leading to possible improvement in treating obesity-related genetic disorders. All this data strongly suggests involvement of eCB system and phytocannabinoids in regulating the gastrointestinal absorption and selectively promoting certain strains that help us with digestion and/or protect us from stress-related pathologies. Consistent reduction in inflammation and affecting gut motility suggests physiological control mechanisms that improve correct functioning of our metabolic system. Promising cancer treatment responses also give hope for development of novel therapies. We have enough scientific evidence to claim the immense impact of eCB system and phytocannabinoids on our gastrointestinal tract, however we must be aware that we need more profound research including clinical trials in order to advance in treatment development. Many key gastrointestinal regulation mechanisms include three key players: gut, microbiota and cannabinoids, opening many possible interactions to be leveraged on in order to create new therapeutical approaches and pharmacological treatments including the use of medical cannabis.
