Recurrent Aphthous Ulcers (RAU) – also known as recurrent aphthous stomatitis – are the most common type of oral lesion. The ulcers present as recurrent round or oval ulcers in the mouth, typically in childhood or adolescence, and are associated with significant pain and implications on patients’ quality of life. While RAU has been associated with immunological disorders, in addition to predisposing factors, including trauma, nutritional deficiencies, food allergies, and underlying medical conditions, the precise cause remains unclear. The oral mucosal condition is more common in females and has a high prevalence, affecting approximately 20% of the general population.
Despite this high prevalence, there is currently no curative therapy for RAU. Instead, treatment focuses on the management of symptoms – primarily on pain relief, reducing inflammation, and promoting wound healing. First-line therapies include topical steroids that can help manage pain and inflammation; however, these are also associated with some undesirable side effects, including oral candidiasis and other infections.
Medical Cannabis and RAU
Due to the lack of curative therapies for RAU, individuals have begun to seek out alternative medications for further investigation in medical studies.
Cannabidiol (CBD) is a non-intoxicating compound that in pre-clinical studies has been shown to reduce pro-inflammatory cytokine expression. It has been theorised that these properties could be useful in the setting of RAU.
A recent study, therefore, aimed to assess the effects of 0.1% topical CBD in order to determine the safety and efficacy of the compound in this setting.
Design and Methods of the Study
The researchers outlined three objectives for the study: (1) to investigate the risk for allergic skin reactions to topical 0.1% CBD, (2) to assess the local and systemic side effects of topical CBD on normal oral mucosa, and (3) to evaluate the effect of topical CBD on RAU.
The study was conducted at the Oral Medicine Clinic, Faculty of Dentistry at Chulalongkorn University in Bangkok, Thailand. The first phase of the study involved a CBD patch test on human skin to investigate any potential allergic reactions to the preparation. The second phase of the study assessed the clinical outcomes of the CBD preparation when applied to healthy oral mucosal tissue.
Finally, the third phase of the study was a randomised parallel double-blind controlled trial to measure the efficacy of CBD for treating RAU. A total of 72 subjects were recruited for participation in the phase 3 trial, all of whom randomly received one of three topical interventions: 0.1% CBD, 0.1% triamcinolone acetonide (TA), or placebo (24 subjects for each intervention) for seven days. If ulcers occurred again, patients could switch to another topical intervention (once 7 days had passed since the previous treatment).
The researchers recorded an ulcer severity score (USS) to indicate disease severity at baseline. This score incorporated six ulcer characteristics: number, size, duration, ulcer-free period, site, and pain. Ulcer size was measured on days 0, 2, 5, and 7. Daily pain ratings were also recorded using a visual analog scale (VAS) ranging from “no pain” to “unbearable pain”, subject satisfaction was rated on a scale of 0 (not satisfactory) to 10 (the most satisfactory), and finally, subjects completed a Quality of Life (QoL) questionnaire at their first and last visit to indicate treatment effects on quality of life.
Results of the Study
None of the participants exhibited any signs of allergic reaction to the topical CBD preparation, as tested in phase 1 of the study. Similarly, none of the healthy subjects who applied the topical CBD preparation experienced or reported an obvious adverse reaction on their oral mucosa. Furthermore, no anaphylactic reactions were observed in the respiratory or circulatory system and no signs of liver dysfunction were reported.
Of the 24 subjects assigned to each of the treatment arms, one patient was lost to follow-up in the CBD group and two were lost in the TA group.
The researchers found that the pseudomembranous ulcer size was almost 100% smaller in patients treated with the 0.1% CBD preparation on day 5 and the erythematous border size was 40% smaller in the CBD group on day 2 compared with the placebo group. Both CBD and TA groups saw a reduction in pseudomembranous ulcer and erythematous border size from day 2 onwards while the average ulcer size in the placebo group increased by approximately 175% and 140% on day 5 and day 7, respectively.
Both active treatment groups showed a reduction in ulcer size at every monitoring point throughout the trial compared with placebo. TA was found to reduce the pseudomembranous ulcer and erythematous border size more than CBD; however, this difference was not considered significant.
Pain Ratings and Patient Satisfaction
Both active treatment groups were also found to reduce pain scores from day 1 onwards, while pain only began to reduce from day 2 in the placebo group. Of the four participants that had been treated with all three interventions at the end of the study period, three ranked TA as their most preferred intervention, followed by CBD; the remaining patient ranked CBD as their preferred intervention, followed by TA.
Quality of Life
Statistical analysis of data from the QoL questionnaires revealed that all three interventions were associated with significantly reduced OHIP-14 scores between baseline and day 7. This indicated an improvement in quality of life.
The findings of this study demonstrate that those individuals who received 0.1% CBD or 0.1% TA had faster healing times compared to placebo. Therefore, the authors of this study concluded that CBD may be considered in individuals who do not respond to first-line, licensed therapies. However, a head-to-head evaluation against topical steroids will be required to determine its relative efficacy and safety compared to first-line therapies.