The huge success rate has nothing to do with changing inflammation in the gut, the most implicated culprit in Crohn’s flare ups. Researchers believe the cannabis may have altered the gut biome to favor beneficial bacteria.
New data has emerged recently at the United European Gastroenterology conference in Vienna showing that cannabis oil significantly improved symptoms of Crohn’s disease and the patients’ quality of life. Most interestingly, the mechanism does not appear to involve resolution of gut inflammation, but rather a change in gut biome. This is in contrast to the previously hypothesized mode of action of cannabis in relieving Crohn’s disease symptoms, since it has been rationalized that the likely therapeutic benefit is conferred via the anti-inflammatory properties of cannabinoids.
In this randomized, placebo-controlled study, Israeli researchers observed that cannabis oil treatment for 8 weeks produced clinical remission in up to 65% of patients without downregulation of inflammation assessed endoscopically. The study included 46 people with mild to moderate Crohn’s disease who were randomized to receive the treatment consisting of 15% CBD and 4% THC in an oil form or placebo.
Inflammation in the gut was assessed endoscopically and with measures of the inflammatory markers in blood and stool samples. Most of the treatment group (15 out of 23 patients) after 8 weeks entered clinical remission compared to the placebo group (8 out of 23 patients). The question then remains: Which therapeutic principles other than anti-inflammatory could this cannabinoid-based treatment be operating on?
The etiology of Crohn’ disease, and inflammatory bowel disease in general, is comprised of at least four factors: genes and genetic predisposition, external environment, microbiome (the ‘good’ bacteria living inside the gut) and the immune response. The most hypothesized candidate to be affected by cannabis-based therapy was the immune system, but this study indicated that this may not be the case.
However, since the environment plays a role in the pathophysiology of Crohn’s disease, and this study was conducted in one geographical location (Israel), these findings are not necessarily easily extrapolated to the rest of the world.
Furthermore, the interactions between genes and the environment further complicate the situation. It has been discovered that about 30 genetic mutations, or changes, are associated with Crohn’s disease. Among these, a small point mutation in the gene encoding one of the inflammatory mediator receptors, interleukin 23 (IL-23).
Additionally, the function of the anti-inflammatory mediator IL-10 has also been associated with Crohn’s disease. Given these mutations in the mediators which play prominent roles in regulation of inflammation, it is difficult to discern whether the study patients showed no reduction in inflammation in response to cannabis oil because of any possible mutations in the relevant genes since no genotyping data has been provided.
If They Had Run The Study Longer, Would Inflammation Have Been Reduced?
Finally, it also remains to be determined whether the duration of the treatment affected the inflammation outcomes, and 8 weeks perhaps may not be enough. Available evidence suggests that adaptive immunity and Th1 T cell recruitment is responsible for the aberrant inflammatory response in Crohn’s disease. This arm of the immunity is slower to develop (takes several days), and thus may take longer to resolve.
Furthermore, one of the effectors is IL-23 for which a genetic mutation has been associated with Crohn’s disease. This highlights the importance of knowing genotypes of patients in clinical trials involving cannabis-based therapy, as possibly different outcomes on inflammation may occur.
Cannabis May Target Gut Biome Populations
Cannabis-based therapy could also target another aspect of Crohn’s disease etiology that doesn’t involve inflammation: the microbiome. There are approximately 1150 bacterial species in the gut that work together with our gastrointestinal system to process food and extract the nutrients. The association between Crohn’s disease and changes of the gut microbiome has already been established, with some studies demonstrating reduced biodiversity and others instability of the microbiome.
Although we are only at the forefront of the microbiome function research, it is known that specific bacterial species live in the healthy gut, whereas another species called enterobacteria is over-represented in the Crohn’s disease gut.
In conclusion, cannabis oil could potentially lead to clinical outcomes by restoring the balance in the microbiome, rather than by resolving inflammation. It could also be that CBD/THC oil sequentially acts on the various aspects of the etiology of the disease, with gut microbiome function resolving first and with prolonged treatment (which may be more than 8 weeks) eventually leading to resolution of inflammation.