Cannabinoids Have Positive Pharmacological Effects on Intestinal Permeability
Cannabinoids are a group of chemical compounds found in the cannabis plant. They occur naturally in the nervous and immune systems of various animals as well. A study has recently been conducted to show that the activation of cannabinoid receptors can decrease inflammation, the secretion of gastric acid, and intestinal motility.
Activation of cannabinoid receptors decreases emesis, inflammation, gastric acid secretion, and intestinal motility. However, the effects of cannabinoids on intestinal permeability have not yet been established. The aim of the present study is to examine the effects of cannabinoids on intestinal permeability in an in vitro model. Caco-2 cells were grown until fully confluent on inserts in 12-well plates. Transepithelial electrical resistance (TEER) measurements were made as a measure of permeability. EDTA (50 μM) was applied to reversibly increase permeability (reduce TEER). The effects of cannabinoids on permeability in combination with EDTA, or alone, were assessed. Potential target sites of action were investigated using antagonists of the cannabinoid (CB)1 receptor, CB2 receptor, transient receptor potential vanilloid subtype 1 (TRPV1), peroxisome proliferator-activated receptor (PPAR)γ, PPARα, and a proposed cannabinoid receptor. When applied to the apical or basolateral membrane of Caco-2 cells, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) enhanced the speed of recovery of EDTA-induced increased permeability. This effect was sensitive to cannabinoid CB1 receptor antagonism only. Apical application of endocannabinoids caused increased permeability, sensitive to cannabinoid CB1 receptor antagonism. By contrast, when endocannabinoids were applied basolaterally, they enhanced the recovery of EDTA-induced increased permeability, and this involved additional activation of TRPV1. All cannabinoids tested increased the mRNA of the tight junction protein zona occludens-1, but only endocannabinoids also decreased the mRNA of claudin-1. These findings suggest that endocannabinoids may play a role in modulating intestinal permeability and that plant-derived cannabinoids, such as THC and CBD, may have therapeutic potential in conditions associated with abnormally permeable intestinal epithelium.
The study was to show what the effects of cannabinoids are on intestinal permeability. Caco-2 cells were grown. TEER measurements were then taken as a way of measuring permeability. EDTA was then applied to reduce TEER, or increase permeability. The results were then assessed to see if the cannabinoids have an effect on permeability as combined with EDTA or alone – or at all.
There were a variety of potential target sites of action investigated using several different receptors as well as a proposed cannabinoid receptor. When it was applied to the Caco-2 cells, several of the cannabinoids showed an enhanced recovery speed of the EDTA induced increased permeability.
Ultimately, the results of the study showed that endocannabinoids have a positive effect on permeability. Apical application as well as basolateral application had a positive effect. These findings tell researchers that cannabinoids can play a significant role in modulating intestinal permeability and that cannabinoids derived from the cannabis plant, including THC and CBD, may have therapeutic properties that can be used in treating abnormally permeable intestinal epithelium.
While medicinal marijuana has been approved in many states, the list of medical reasons for prescribing the medicinal marijuana is still very limited. Some states will only use it for glaucoma and chronic pain while other states will allow it to be used for various other purposes as well. As the federal government is still determining whether medicinal marijuana should be approved across the country, research has been continuous to show all of the positive effects. If the cannabinoids can be proven to provide yet another positive effect on health, it is one step further to allowing medicinal marijuana to be prescribed to more patients around the country.