With 3 million people from the U.S. reporting clinical cases in 2015 – accompanied by an increased projected incidence in Western civilizations – inflammatory bowel disease (IBD) is a rapidly growing concern for younger adults in their 20s and 30s.
Current IBD therapies involve suppressing the dysfunctional immune response, which has numerous collateral side effects that can become highly harmful for usage over the long term. Several alternative routes for treatment are currently being interrogated by researchers, many of whom have shifted their attention to investigating the involvement of aberrant permeability in the gastrointestinal epithelial.
Although the entirety of IBD’s pathophysiology is unknown, research has identified a number of genetic and environmental factors that potentially contribute to the onset and progression of intestinal disorders. Notable factors implicated include steadily elevated production of reactive oxygen and nitrogen species (ROS-NOS) in response to oxidative stress and altered intestinal epithelium permeability.
With the recent identification of a functional enteric endocannabinoid system (ECS) within the human gut, compounds isolated from Cannabis sativa L. are especially gaining traction among the clinical community as potential adjuvant treatments for IBD management. Mounting scientific evidence supports reports of Cannabis inducing analgesic and anti-inflammatory effects in intestinal disorders.
But which cannabinoid compound would offer the most effective therapeutic benefit?
According to a recent study published in Frontiers of Pharmacology, the ‘King Cannabinoid’ for IBD treatment may be the clinically multifarious cannabidiol (CBD).
In the study, investigators sought to determine the effects of compounds isolated from C. sativa L. on an in vitro model of intestinal epithelium. More specifically, they aimed to investigate the capacity of these compounds to modulate intestinal barrier permeability and gut inflammation following exposure to oxidative stressors and inflammatory stimulants – both of which are implicated in the pathology of IBD.
Compounds were isolated from C. sativa L. extracts using supercritical CO2 (scCO2) extraction, which were identified as Δ9-tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBD-A), and cannabidiol (CBD). The in vitro cell cultures were treated with each of these compounds under three different conditions: basal (cannabinoid treatment only); following peroxide treatment (to serve as an oxidative stressor); and following inflammatory stimulation with interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNFα).
To investigate each cannabinoid’s capacity to mitigate processes associated with intestinal dysfunctions, ROS production was measured along with transcellular and paracellular permeability. Immunofluorescence (IF) assays were used to assess ROS production, and transepithelial electrical resistance (TEER) was used to measure permeability.
THC was able to partially ameliorate the oxidative effect of peroxide treatment by decreasing ROS production following exposure, but was unable to mitigate its effect on permeability (denoted by decreased TEER values). CBD, however, was able to decrease ROS levels and also maintain TEER within a normal range (comparable to controls).
Following exposure to inflammatory stimulants, THC and CBD both demonstrated protective effects on TEER, but with THC only being significantly effective at one concentration whereas CBD was effective at two different concentrations.
From these experiments, the researchers suggest that CBD plays a protective role – potentially along with THC – in maintaining gut homeostasis. They conclude based on their results that the most effective C. sativa L. compound (of those analyzed within the study) for the treatment of intestinal inflammatory conditions is CBD due to its capacity to restore epithelial permeability following exposure to oxidative and inflammatory stressors. They extend this concept further to suggest CBD as a potential therapeutic intervention for IBD.
Sources: Centers for Disease Control & Prevention (CDC); CDC’s Weekly; The Lancet; BMJ; Frontiers in Pharmacology