The results of a recently reported pilot study of a randomized, parallel group, double-blind, placebo-controlled trial utilizing a botanical Cannabidiol (CBD) extract for treatment of ulcerative colitis (UC) found the treatment promising, amid challenges in protocol. Adult patients with extensive or left-sided UC were identified based on Mayo score, endoscopy score, and who had been on a consistent dose of an aminosalicylate for their symptoms of UC.
The study is of interest for multiple reasons.
First, there are few studies utilizing cannabis related compounds that are designed similarly to a clinical trial due to the challenges of legality in the US and funding concerns for research focused institutions. This particular study was completed by researchers in the United Kingdom and supported by the National Health Service trust in England. This was an interventional treatment trial and the group randomized their study participants in a 1:1 ratio for their experimental and placebo comparator arms. The administration of interventions/placebo lasted 10 weeks. It is encouraging to see increased published research that is not based on anecdotal evidence and is not a review of existing research. This is a challenge globally in the area of cannabis science. To determine medicinal value and risk, as well as gain respect and credibility with the providers who care for patients (not to mention government officials capable of enacting policy change), new and novel approaches with well-designed studies need to be completed and shared.
Second, the group used a botanical CBD extract that they described as “CBD-rich”. Botanical cannabis products can contain more than just CBD which researchers know is beneficial to patients because of how the different compounds work together to act on the body’s own endocannabinoid system. The particular CBD extract, called GWP42003, contained 4% delta,9-tetrahydrocannabinol (THC), and the group suggests that some of their protocol challenges resulted from individual reactions to the presence of the amount of THC. Approximately 41% of participants in the experimental arm deviated from the protocol to maintain their goal of 250mg b.i.d. treatment for the full 10 weeks after the initial 2-week titration to this maximum dose. The authors of the published work indicated they created a sub-group within the experimental arm that actually maintained the protocol (grouped as “per protocol” or “PP”) and this group’s findings and results were compared to the placebo group and remaining experimental arm that did not achieve and maintain the maximum dose of their intervention. What is noteworthy is the recognition that the protocol deviations allowed for an additional observational opportunity. The delivery mode of the intervention was a hard gelatin capsule and multiple had to be taken at a time; an area to continue to evaluate is examination of delivery mode as it may also have had an effect on protocol compliance.
The third interesting aspect to this study is the analysis that found that the 59% of PP participants in the experimental arm had observed remission rates of 28% and the other 41% of participants that were non-compliant with treatment was 26% and not statistically significant. Even some CBD was perceived as effective, even if not the maximal dose determined as the study’s initial target. Additionally, the PP Mayo score changes compared to the partially compliant treatment group’s Mayo score changes were found to be statistically significant. The reported non-gastrointestinal (GI) associated AEs were not severe and more often reported in the GWP420-03 group which the authors attributed to the percentage of THC affecting individual participants. A high proportion of GI-associated AEs were seen in the placebo group and those volunteers had a worsening of their UC.
Supporters of medicinal cannabis often talk about the benefits and evidence for how it has helped so many people; this study discussed both the benefits, challenges, and potential risks related to THC symptoms as AEs for individual participants. More studies like this are needed to fully elucidate the topic of medicinal cannabis (including related compounds) and its potential.